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August 18 2015

2015PreventingDrunkDriving

Lowenstein Sandler Adds Top White Collar Defense Attorney to Leading Practice | Reuters

Lowenstein Sandler Adds Top White Collar Defense Attorney to Leading Practice

Lowenstein Sandler LLP added strength to its exceptional White Collar Criminal Defense Practice with another outstanding addition: Paul Weissman joins the firm as senior counsel with false arrest lawsuit than 30 years of white collar and pharmaceutical industry litigation experience.He will serve clients from the firms offices nationwide.

Mr. Weissman was an Assistant U.S. Attorney in Newark from 1982 to 2002. Serving as Deputy Chief of the Fraud Division and Chief of the Financial Institution Fraud Unit, he conducted and/or supervised the prosecution of numerous high-profile securities, tax, bank and health care fraud cases. He then served for more than a dozen years in the pharmaceutical industry, first as Schering-Ploughs Staff Vice President for Compliance and then as a Managing Counsel at Merck, after it merged with Schering-Plough.

With his extensive, high-level prosecutorial and corporate experience, Mr. Weissman offers clients a truly multidimensional perspective. He understands first-hand how the government investigates and prosecutes fraud, and how corporations must manage investigations, regulatory compliance and litigation. Having managed teams of outside lawyers at Merck and Schering-Plough, he understands how clients want to be served.

Lowenstein Sandlers long-term strategy is to grow by doubling down on core areas of strength that match the marketplaces growing demand for certain legal services. Within the past two years, the firm has added to its roster of widely respected white collar defense attorneys several notable figures. In addition to Mr. Our Team of Legal Experts Focus on Your Rights & Trying to Dismiss Your Charges Why Us; Years of Proven Experience, Aggressive and proactive approach, High degree of skill, experience, and understanding, Top-quality legal advice and representation, Protect Your Rights, Negotiate Strong Plea Bargains, 24 hours a day, seven days a week.Weissman, the firm has welcomed Matthew Boxer, former Comptroller for the State of New Jersey; Shavar Jeffries, former Special Counsel to the New Jersey Attorney General; make a will Maureen Ruane, former Chief of the Healthcare and Government Fraud Unit of the U.S. Attorneys Office in Newark.

Gary Wingens, Lowenstein Sandler Chairman and Managing Partner, said, Paul is a great fit per our long-term strategic plan. His distinguished background as what is legal punishment Assistant US Attorney and counsel to major pharmaceutical companies will add new dimensions to our core white collar practice as well as our corporate life sciences team. He understands business and possesses empathy for clients that springs from first-hand experience. And he is a genuine person who cares for his peers. We are excited to welcome him to the firm.

Michael Himmel, Chair of the White Collar Criminal Defense Practice, said, The health care industry has been beset by an increasing number of investigations of its conduct, from states attorneys general to US Attorneys to federal regulatory agencies. Were seeing increased demand for our services, as health care providers are now just as open to scrutiny as manufacturers. With his experience in government and on the corporate side, Paul will be a valuable asset to our clients and a fantastic addition to our team.

Mr. Weissman said, Lowenstein Sandler offers exactly what I was looking for in private practice: the scale and depth to serve the largest clients at a manageable size that supports a collegial environment and strong personal relationships with clients and fellow attorneys. The white collar defense practices reputation is first-rate, and I look forward to making a contribution to the firm and its clients.

Paul earned his J.D., cum laude,from Harvard Law School, and his criminal case lawyers.B., magna cum laude,Phi Beta Kappa,from Harvard College.Prior to law school, he was a Ph.D. student in history at Harvard University.

About Lowenstein Sandler

Lowenstein Sandler is a leading national law firm. Our 300 lawyers in New York, Washington, DC, New Jersey and California immerse themselves in our clients' industries in order to deeply understand their businesses. We are characterized by our passion for our clients' success, our commitment to our people, and our pro bono and public interest work in the communities that we serve. For more information, please visit www.lowenstein.com.



View source version on businesswire.com: http://www.businesswire.com/news/home/20150716005204/en/



Press Contact:

Lowenstein Sandler LLP

Andrea Sheehy

Tele: 973.422-6758

http://www.reuters.com/article/2015/07/16/ny-lowenstein-sandler-idUSnBw165204a+100+BSW20150716

2015PreventingDrunkDriving

Sheppard Mullin Grows Washington, D.C. Office; Firm Welcomes Three Experienced Litigators

WASHINGTON--(BUSINESS WIRE)--May 6, 2003--Sheppard, Mullin, Richter & Hampton LLP announced that John R. Fornaciari has joined the Firm as a partner, and Robert M. Disch and John J. Vecchione have each joined the Firm as senior attorneys. Fornaciari specializes in the trial of complex commercial cases, antitrust litigation and white-collar criminal defense. Disch focuses his practice on commercial litigation with a specialty in antitrust law. Vecchione practices general litigation, primarily in the context of commercial and employment law.

"We are excited to add these three talented attorneys, with outstanding litigation capabilities and wide-ranging trial experience," said Guy Halgren, Chairman of the Firm's Executive Committee. Also commenting on the lateral additions, Administrative Partner of the Washington D.C. office Bob Magielnicki said, "Seasoned litigators are critical in order to properly serve clients. The integration of these three attorneys adds to the Firm's already formidable litigation resources across the country."



Fornaciari has handled trials nationwide, involving antitrust claims, RICO claims, fraud, freeze-out mergers, breach of duty, conspiracy, mail fraud and wire fraud. Fornaciari received his law degree from Boston College in 1971, and his undergraduate degree from Providence College in 1968. He is a member of the American Bar Association, and is admitted to practice in the District of Columbia, the Commonwealth of Massachusetts; the U.S. Supreme Court; U.S. Our Team of Legal Experts Focus on Your Rights & Trying to Dismiss Your Charges Why Us; Years of Proven Experience, Aggressive and proactive approach, High degree of skill, experience, and understanding, Top-quality legal advice and representation, Protect Your Rights, Negotiate Strong Plea Bargains, 24 hours a day, seven days a week.Courts of Appeals for the First, Second, Third, Fourth, Sixth, Seventh and Federal Circuits; the U.S. District Courts for the District of Columbia, Maryland, Massachusetts and Connecticut; and the U.S. Tax Court.

Focusing on commercial litigation and antitrust law, Disch has handled complex commercial litigation matters arising from bank failure; defense of corporate officers and directors; defense of antitrust suits; defense and prosecution of defamation and trade libel suits; and white-collar criminal investigations and trials. Disch also specializes in matters relating to the Hart-Scott-Rodino Act. Disch received his law degree from Northwestern University in 1981, and his undergraduate degree from Carroll College in 1978. He is admitted to practice in the District of Columbia; the U.S. Supreme Court; U.S. Court of Appeals for the District of Columbia Circuit; and the U.S. District Court of Maryland.

Vecchione has extensive experience litigating contract criminal attorney commercial matters, and defending equal employment opportunity claims. His experience includes UCC check fraud cases, maritime torts, antitrust, white-collar and securities litigation. Vecchione received his law degree from Georgetown University Law Center in 1989, and his undergraduate degree from Hamilton College in 1986. He is admitted to practice in New York and the District of Columbia, as well as Maryland Federal District Court.

Sheppard Mullin has reasons against capital punishment-difference-between-dui-and-dwi/">advantages of right to jury trial in criminal cases jury trial than 370 attorneys among its eight offices in Washington, D.C., Los Angeles, San Francisco, Orange County, San Diego, Santa Barbara, West Los Angeles, and Del Mar Heights. The full-service firm provides counsel in Antitrust & Trade Regulation; White Collar and Civil Fraud Defense; Business Litigation; Construction, Environmental, Real Estate & Land Use Litigation; Corporate; Entertainment, Media & Communications; Finance & Bankruptcy; Financial Institutions; Government Contracts & Regulated Industries; Healthcare; Intellectual Property; Labor & Employment; Real Estate, Land Use, Natural Resources & Environment; and Tax, Employee Benefits, Trusts & Estates. The Firm celebrated its 75th anniversary in 2002.

http://www.businesswire.com/news/home/20030506005694/en/Sheppard-Mullin-Grows-Washington-D.C.-Office-Firm

August 13 2015

2015PreventingDrunkDriving
Topics concerning life in prison no parole http://goo.gl/Gn682U #UnitedStateConstitution

July 22 2015

2015PreventingDrunkDriving

Thursday Gather Writing Essentials - Road Trip - Going away again



My mom headed on a long road trip with my niece, 2, nephew, 5, and my brother and sister-in-law. They headed to Florida. During the trip down to Florida they stopped capital punishment for and against Pedro's and got to see how the old statue and tourist trap was getting along. Famously.

Than my family went to Florida. While there they got to see a lot of old and new exhibits in Walt Disney World and Sea World. My family had so much fun with their grandmother and Florida that they never wanted to come back home.

capital punishment where is it legal the mean time while they where having their adventure I was stuck with the snow and ice up here in New England. I wished that I had somewhere to go somewhere to not be stuck here in the snow and ice. Well my councilor got involved with my workers and I am going again to weight loss camp. While everyone had fun on their trip on mine I will be monitored and locked in a locked down hospital stay. Oh what fun that will be. Oh well I should not ask for much and I should not wish I was somewhere else. I need to relieve that this is the best for my eating disorder and my anxiety.

Got to fly.

Amy

As always there are a few guidelines on Thursday's Challenge that we need to follow. Looking for information about ? death penalty statistics 2015 auto injury reviews will give you some good insights.They are the usual ones that we ask you to follow each Thursday. One guideline to remember is to include the words Road Trip 4/4/2013 somewhere in https://www.law.cornell.edu/constitution/preamble href="http://www.gaiaonline.com/journal/?mode=view&post_id=37222577&u=38188187">the title.

A second guideline is to be sure to tag it with Thurs or Thursday Writing Essentials, Thursday Gather Writing Essential,Road Trip Don't forget to Post your post to Gather Writing Essential.

court ordered community service third guideline is to not forget that there is a limit of three submissions from each member per day. If you're extremely prolific, spread out your work and post only three submissions per day.

** Again I still have not reached a point where my plate is clear enough to be able to post a list of the responses to Thursday's Challenge. It is still my intent to to finally do that ASAP but it won't be this week either. I am very sorry.  I am getting closer and closer to being able to do it though.

http://gather.com/thursday-gather-writing-essentials-road-trip-going-away-again/

2015PreventingDrunkDriving

Driver has lucky escape after sinkhole swallows up car on busy China motorway

By

Mail Foreign Service

Updated:

11:16 GMT, 14 June 2010

A motorist had a lucky escape after his car was swallowed by a sinkhole as he travelled along a http://en.wikipedia.org/wiki/Preamble_to_the_United_States_Constitution busy motorway.

The vehicle was trapped, with its front wheels sunk into the chasm, when the gap, measuring about 13ft-wide, suddenly appeared.

The sinkhole - which is the eighth discovered in China in the past two weeks - happened in Nanchang City, capital Jiangxi Province.

Trapped: The vehicle is stuck after a sinkhole opened up <a href=for capital punishment facts Nanchang City" class="blkBorder" />Trapped: The vehicle is stuck after a sinkhole opened up in Nanchang City

Balancing act: <a href=the death penalty statistics-department-of">the ground opened up in the middle of the car as it travelled along the motorway" class="blkBorder" />Balancing act: The ground opened up in the middle of the car as it travelled along the motorway

More than 35 have been found since April.

It comes after punishment for homicide href="http://workaccidentinjury2015.postbit.com/blues-royalty-b-b-king-dead-at-age-89.html">a factory and an entire intersection were gulped down by a 100ft deep and 66ft wide sinkhole following a tropical storm in Guatemala last month.

In China, 600 villagers were evacuated after four huge voids opened up in Guangxi Province.



what is consecutive sentencing car accident lawyers attorneys reviews will give you some good insights.ailymail.co.uk/i/pix/2010/06/12/article-1286026-09FE4D90000005DC-776_634x822.jpg" height="822" width="634" alt="The vehicle is lifted to safety after the busy motorway is closed" class="blkBorder" />The vehicle is lifted to safety after the busy motorway is closed

Common: A truck overturned and its driver was injured after a hole appeared in a motorway in Zheijiang ProvinceCommon: A truck overturned and its driver was injured after a hole appeared in a road in Zheijiang Province

Three smaller holes were discovered in May in southwestern Sichuan Province, less than 80 miles from the earthquake in 2008 in which 80,000 people died.

In another incident, a truck overturned and its driver was injured after a hole appeared in the middle of a motorway in Zheijiang Province on the nation's eastern coast.

The sinkhole measured 20ft deep and 27ft wide.

Devastation: A factory and intersection were swallowed up by a 66ft-wide sinkhole that opened up after storms in GuatemalaDevastation: A factory and intersection were swallowed up by a 66ft-wide sinkhole that opened up after storms in Guatemala

A spokesman for the freeway management office said experts on site suspected that the sudden collapse of an underground karst cave created by eroded limestone caused the sinkhole, but the investigation is ongoing.

In Yibin City, about 260 miles from the earthquake's epicentre, 26 larger sinkholes have formed in the past two months.

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2015PreventingDrunkDriving

The Evil Stepmother - InfoBarrel

Martha Rendell

Criminals are not born that way.  There is no genetic component to criminality.  Sadistic serial killer Ted Bundy (b: 1946 in a home for unwed mothers; executed: 1989), for example, was raised by grandparents (not criminals).  His biological mother later married and took care of him; her new husband, John Bundy, formally adopted the boy.  Neither of his parents were criminals. 

Environment alone does not always lead to criminality, either. It may, in certain people, create a laissez-faire attitude but it will not make a criminal of someone not already predisposed, for whatever reasons, to be criminal.  The Menendez Brothers (parricides) were born into privilege.  Their environment (regardless of their defense pleas in court) was not classically "bad" or harmful.  They enjoyed wealth and comfort.  Likewise, America's earliest youthful killer, Jesse Pomeroy, came from a solid background.  His parents were married and in a stable relationship, and both were gainfully employed (Pomeroy's mother ran a dressmaker's shop where Pomeroy would later lure and kill a young girl, burying her in the ash heap of the basement).  These two minor examples show how environment had no hand in creating the criminal.

A criminal's behavior can be informed by his early environment, however.  Cult leader Charles Manson and serial killer Henry Lee Lucas are two stellar examples of environmental factors shaping the young psyche.  Manson (who actually never killed anyone personally) and Lucas were both http://en.wikipedia.org/wiki/Preamble_to_the_United_States_Constitution born of prostitutes.  Manson's mother was a hapless train wreck; Lucas' mother was an outright monster (and is a perfect example of how environment

can create a killer).  In any event these two were raised in a milieu where criminality was accepted, acceptable, and even condoned. 

Finally, one has the criminal "victim".  Prisons are full of innocent people - just ask any inmate.  He or she will generally claim innocence, or a frame-up, or accident, or bad legal representation.  Almost any excuse is acceptable but the truth: he or she may actually be guilty of a crime. There are others who, of course, blame their lack of education or their upbringing, or blame the current state of human morals and norms for their problems.  The statement, "I'm a victim of society," has been heard more than once from a defendant. 

However, what happens if one truly is a victim of society?  For Martha Rendell, Australia's turn-of-the-20th Century Evil Stepmother, it meant execution by hanging.

The Merry Old Land of Oz

Australia was born of a strange dichotomy in its group think.  The settlers of Botany Bay were not "settlers" in the traditional sense but transported British criminals.  Australia's founding as another country's dust bin is perhaps not the most glorious of beginnings, but it is the truth.  The law-and-order element of the British Crown enforced Australian rule, while its growing populace carried the memory of a criminal culture with them.

Australia has a richly colorful history of extraordinary characters.  Their myth-making is a fascinating reminder of the culture's embrace of both the eccentric and the truly criminal on a

romantic level.  One of Australia's more notorious outlaws was a bushranger named Ned Kelly who thwarted police capture and repeated shootings by devising a rough suit of armor from scrap material.  Illustrations of him in this makeshift gear are amusing - he looks like a cross between the Black Knight (of Monty Python and the Holy Grail) and a man wearing a Franklin stove.  Merriment aside, this man was a killer and a thug (finally captured and executed in late 1880, aged 25).  The press and public, however, loved him, and he was an "outlaw" imbued with all the romance and intrigue of a Strine version of Robin Hood.

Not all criminals in Australia rose to Ned Kelly's level of public adoration.  One woman was so loathsome (in her homeliness, rough-hewn ways, and lifestyle) that she was accused, convicted, and executed for killing three of her "stepchildren".

The Wicked Witch of the West

Adelaide, Southern Australia, incorporated in 1840, was a rustic backwater not yet fifty years old when Martha Rendell was born on August 10, 1871.  Australian conventions followed the Crown's behavior, and the remoteness of the land meant it was not only slow to adapt to newer conventions it was also slow to shed old ones.  Victorian priggishness was in full swing.

Martha was not the typical Aussie woman of her day, and she was far from the ideal espoused by Aussie convention.  She left home when she was sixteen.  Her early promiscuity led to the birth in quick succession of three illegitimate children.  She struggled along as a social outsider, and then became involved with a married man in the mid 1890s.

Thomas Nicholls Morris(Martha's love interest) and his wife lived with their nine children.  In 1900 Morris and his family decamped for Perth where Thomas had work waiting for him.  Thomas and his wife were also motivated to leave Adelaide simply because, in the small gossipy town, Martha's affair with Thomas was not tolerated and was considered scandalous.

Martha, against all common sense and social expectations, abandoned her three children in Adelaide, and followed the Morris family to Perth [Although it is not known what mode of travel was used, to give an idea of just how great an undertaking this was, Perth is almost 1400 miles west by coastal shipping lanes from Adelaide.  It was not a trip one would make recklessly in 1900, either overland or by ship]. 

Perth (the capital of the state of Western Australia) lay about nine miles north-northeast of the busy Indian Ocean port of Fremantle.  The site where the city stands was first visited by the Dutch in 1696; however, no settlement was established until the British set up shop in 1829.  The town was incorporated in 1865 and included the port of Fremantle in its metropolitan area.

A gold rush brought wealth and opportunity for many and by the time of Martha's and Thomas Morris' arrival it was a city on the cusp of urbanizing and becoming acculturated to the finer things.  International social movements took hold, although with a slightly more conservative bent.  The city was likewise divided along class lines just like Britain.  There was the old guard, fiercely loyal to the British Crown and British Victorian sensibilities.  Then there were the hoi polloi, just trying to get along as best they could. It was from the moneyed and powerful class that Perth's legal contingent was made, and they vigorously supported capital punishment.

Perth gave both Thomas and Martha a fresh start. Neither was known there; the anonymity relieved the stress of their continuing affair. Martha found a job straightway as a domestic in a well-heeled household. Martha, because of a wildly effective Women's Suffrage movement, had the right to vote in Perth (the right was granted in 1899, 21 years before the United States would allow women the right to vote).  The suffrage movement, however, came with a few caveats: although suffragettes lobbied for better treatment under the law and protection in the home, they upheld the popular ideals of female domesticity, respectability, and morality. Despite the opportunities available to her, however, she was still attached to Thomas Morris, and her future actually was heavily dependent upon his whims.  If something went awry in her affair with him she could not go back to Adelaide as she was a pariah there.

Social pressure about populating the country for its betterment was so great that women were encouraged to have as many children as possible.  Social Darwinism was at work behind the scenes, too.  A loose group of doctors and scientists, most of them new to Perth, were alarmed by evidence of population decline, poor health, "racial degeneration", and moral "deviance and contagion".  This was attributed to the rapid social changes inspired by the social movements embraced by the community (suffrage, labor, etc.).  Perth's citizens believed the family was the social powerhouse of the new Australian nation.  Motherhood was held up as a shining beacon of virtue, as was Christian marriage.  Another critical element of this Progressive program was to insure the health of children through government intervention.  A medical officer in 1907 reported critical issues involved "schoolchildren's health, pulmonary disease among miners, historico-epidemiological studies of tuberculosis and diphtheria, quarantine, diet, housing, eugenics".

The last social issue affecting Thomas and Martha was the divorce debate.  However much "in love" Thomas Morris and Martha Rendell were they could never marry, not in Perth society in that era.  Divorce was out of the question.  It was expensive, scandalous, and controversial. In a public forum in 1901 speakers opposed a federal divorce bill, reasserting that "Christian marriage" was the "foundation of the state and of the welfare of its citizens and their happiness and prosperity". Opponents alleged making divorce easier would "open the floodgates" to adultery and orphaned children, and it was the state's duty to "protect the family, punish severely all transgressions, and assist the injured".

Public opinion had spoken.  Thomas Morris and Martha Rendell maintained their surreptitious relationship for a few more years.  In April 1906 (after almost ten years of sneaking around with Martha), Thomas Morris abandoned his wife.  He could not divorce her, but he did leave her.  He also took his five youngest children with him [it is curious to note the children did not stay with their mother.  This begs the question of just what kind of woman the Mrs. Morris was if, in 1906, it was deemed more fitting for the children to live with a single father]. 

Martha and Thomas set up housekeeping with the children in a run-down shack in East Perth.  Martha had to pretend to be Thomas' wife or else face social ostracizing - many couples who wanted to cohabit were forced to live in this fashion.  Their new residence was ideal to keep up the sham marriage image - the area was filled with transients who took little interest in their neighbors.  To support the charade, the children's real mother was kept away from the home (and none of the children would see her for three years after Martha and Thomas took up living together).

Martha's life with Thomas Morris was not the idyll she probably imagined.  They lived in poverty.  Her days were spent in housework. Thomas was away much of the time working, and he left her as the sole warden of his five very resentful children.  The girls were too little to help with the household chore, and the older boys had school and outside jobs to keep them occupied.  Martha spent her days mostly alone.  She had no friends or family and she was not close to her neighbors. 

The most common version of what happened to Morris' children after Martha moved in is well-known to the Perth community.  Martha Rendell holds a place in Perth lore equal to Belle Gunness (America's lonely hearts killer and murderer of her own children during the early 1900s). 

The basic story is simple.  Between July 1907 and October 1908 it is alleged that Martha Rendell systematically killed the three youngest children of Thomas Morris, and made an attempt on the life of the next to oldest (George).  In a very contrived and subtle killing method Martha Rendell allegedly coated the backs of the children's throats with a solution of hydrochloric acid (which was called "spirits of salts" then) after somehow making the child victim sick first (so "treatment" could be administered without suspicion).  The inflammation from the swabbing closed the child's throat, while also mimicking the symptoms of diphtheria, and the child died of starvation, a long, drawn out process.

The first child to succumb was Annie, aged 7. Using the method of coating the throat with hydrochloric acid Martha killed the girl.  She died on July 28, 1907. Dr. James Cuthbert, the Morris family physician issued a death certificate, listing the cause of death as diphtheria.

Olive, age 5, died next.  She exhibited similar symptoms as Annie before her death on October 6, 1907. Dr. Cuthbert issued a certificate, also giving the cause of death in the case as diphtheria.

The 14-year-old Arthur was targeted.  He was the middle child and the youngest one still living in the cottage.  After malingering he died on October 6, 1908. Given that this was the third child to die in the household under similar circumstances, Dr. Cuthbert asked Martha if he could do an autopsy on Arthur.  She gave her permission, and was also present during the procedure.  Nothing incriminating was found at the time of the autopsy.

In April 1909 the second oldest boy, George (age 15), complained of a sore throat "after drinking a cup of tea" Martha had made for him.  According to the boy's allegations, Martha coated his tonsils with "her medicine".  George decided he "didn't want to go the same way" as his two younger sisters and his younger brother had, so he ran away from home to his biological mother a few streets away.

That day when Thomas came home from work he noted George's absence. When questioned by a neighbor as to George's whereabouts Thomas replied he did not know.  Suspicious, considering three children had already died over the last two years and now one was missing, neighbors went to the police. 

Inquiries started by an inspector named Harry Mann.  He was given lurid details from the people in the area about the children having their "throats painted" and their mother's (Martha's) apparent indifference to their pain and screaming.  Those who knew her a bit claimed she had a vicious nature and was not liked. It was alleged she mistreated the two young girls, once beating the girl Annie so badly that she could not walk.

One resident claimed he often peered in the windows of the Morris home.  At those times, this neighbor claimed he saw Martha standing before whatever child was screaming, "rocking back and forth as if in ecstasy".  Inspector Mann found the runaway boy George Morris at his biological mother's home.  At the time of his return, George made the serious allegation that Martha had killed his brother and two sisters, and she was trying to poison him, too.

Rendell and Thomas Morris were both charged with murder, Thomas as an accomplice.  Martha protested her innocence, saying she had been treating the children for diphtheria and they simply died of the disease. The arresting officer, Harry Mann, said Martha "delighted in seeing her victims writhe in agony, and from it derived sexual satisfaction".  The press gleefully repeated it.

The Wicked Witch Is Dead

The coroner's inquiry was confounded by the time lag since the deaths and the discovery of a possible criminal act.  Doctors could not say what effect swabbing with hydrochloric acid would actually have on a child's throat.  The inquest panel found suspicion in Martha's purchases of large quantities of spirits of salts during the time of the children's illnesses (coupled with her buying none since the latest child, Arthur, died). A court order was obtained to exhume the children's bodies, and this was done in July 3, 1909 (almost two years after Annie died, 21 months after Olive died, and eight months after Arthur died).  Diluted hydrochloric acid was claimed to have been found on the throat tissue of each child. 

The public's outrage was fantastic over office location allegations, not so much about the children's deaths but about Martha's amorality. The press painted her as a "scarlet woman" and called her a "wicked stepmother".  At trial, Thomas Morris, the father, was acquitted, and Martha was handily found guilty by an all-male jury.  She was convicted only of killing Arthur as not enough evidence could be produced to convict her of killing Annie and Olive.  She was sentenced to death, and was hanged on October 6, 1909 (coincidentally the first anniversary of the boy Arthur's death).  She was the last woman executed in the state of Western Australia.  Martha Rendell is buried in the famous Fremantle Cemetery (in the same grave where, for unknown reasons, serial killer Eric Edgar Cooke was buried more than fifty years later).

"If I Only Had A Brain"

Martha Rendell was an unattractive, aging, home-wrecking trollop who abandoned her own three children to follow a man across country.  She was all of these things, contemptible to Perth society of the early 1900s, but she was not a killer.

The criminal case against Martha shreds easily.  This is a clear instance of societal prejudices putting a woman to death simply because she was not liked, and she did not live by the "right" rules.

Martha Rendell was irascible.  She did not get on well with others.  When her sham marriage to Thomas Morris was uncovered, upon her criminal arrest the public outrage was very real and very vocal.  Martha did not live by the rules of the day.  She had "stolen" another woman's husband (never mind that her relationship with Thomas lasted from 1896 until her arrest in 1909 and that Thomas had abandoned his wife). 

Martha knew she would be in trouble if anyone found out the illicit nature of her living with Thomas.  Hence, she used the name "Mrs. Morris" and required the children to call her "mother".  This only makes sense.  Additionally, the claim she had beaten the girl Annie to the point where she could not walk may be true.  However, Martha would not have been the first or last person in that era to abuse a child in the name of "discipline".  That does not excuse the behavior, but much was made of it - had the police bothered to dig into that neighborhood's other denizens they would have found child abuse and neglect elsewhere as well.

The state of affairs for children in Perth was not good, particularly the children of the impoverished.  Women could find jobs, and they were welcomed in the workforce, but with child care expectations generally thrust upon them they could only hope to work.  "Baby farming" came into vogue to help the working poor woman.  Baby farms provided a service for working single mothers follow us on twitter deserted wives (with no divorce option, there were many) who were forced to leave babies and small children in care while they earned a living (forerunners of day care).

Unfortunately for Martha, a case was still ripe in the public mind when she came to trial. In early 1907 there were reports that 37 children had died at a Perth baby farm run by a woman named Alice Mitchell.  These farms were routinely inspected and surprise visits were not uncommon by authorities, either.  Mitchell's business had been receiving favorable inspection reports, but doctors who regularly signed death certificates did not think anything untoward was happening at her farm.  The doctors in this negligence case were absolved of responsibility by the court (a precedent that would adversely affect Martha later).  Alice Mitchell was ultimately charged with only one count of murder.  She did not hang, however; confusion at her trial combined with contradictory circumstantial evidence led to her only receiving a five-year sentence at hard labor [Alice Mitchell was in the Women's Division of Fremantle Prison when Martha Rendell arrived in 1909 to await execution].

Martha alleged the children had diphtheria and she was only treating them for that illness. This bears the clear ring of truth.  Diphtheria and typhoid were major problems, and killers of many, in the world at that time.  In the US, people actually moved away from New Orleans, Washington, DC, and other larger cities for the summer months (if they could afford it) to wait out the "fever season" in cleaner climates.

In the cramped poverty rows, like where the Morris family lived, disease was not uncommon and it certainly flourished.  These are people who used home remedies and could not afford to avail themselves of consistent physician's care.  The government would send health inspectors around if a complaint about unsanitary conditions in a particular home was lodged (as part of the Progressive child-care agenda) and Martha Rendell was paid one of those visits unannounced.  She passed her inspection.  So, the children were not being neglected.

For the first year of living together Martha and the five children had to acclimate to each other.  Their own mother was purposely not in the picture.  Thomas reported his children did not care for Martha, and she was probably not the most pleasant candidate for a stepmother - she was lonely, aging, and bitter, without a true sense of stability that marriage could bring (in a society that valued it highly).  Furthermore, she lived in constant fear of being discovered in her sham circumstances and facing the same public humiliations she endured in Adelaide.  

In April 1907 all four of the youngest children caught diphtheria.  This was actually part of a city-wide epidemic that raged through Perth at the time.  The health care workers and doctors of the day were stressed immensely with health care demands they had neither the resources nor the staff to address.  Many people had to fend for themselves of necessity. 

Diphtheria is a horrible disease, highly transmissible, and it kills by spreading bacterial toxins through the blood.   Martha would have had to nurse four feverish, whining, sick children at once.  Their breathing was harsh and raspy - any breaking of the swollen tissues in their diphtheria infected throats meant fatal toxicity to the body.  Dr. James Cuthbert (who gave damning evidence against Martha at her trial) was the Morris family physician, and during this critical period he visited the Morris home on many occasions (he actually later commended Martha on her devotion to her nursing of the children, risking her own health in the process).

This presents the first and largest hole in the prosecution's case against Martha.  The alleged method of death, the subtle poisoning to constrict the throat causing breathing difficulties and an inability to eat, is absurd on its face.  In the first place, just what strength solution of hydrochloric acid was needed to carry out this artful murder?  Too much and the victim would die instantly.  Too little and nothing would happen except a throat irritation. Martha was no chemist - this uneducated woman would have had to experiment tirelessly on some living thing before getting the mixture right.  The "hit-or-miss" uncertainty of such a method leaves it outside the realm of not only probability but of possibility as well.  Although there are many cases of murder with poisons (heavy metals such as arsenic, antimony, thallium, etc.) and some cases of people killed with acids (sulfuric, specifically) none had ever been recorded meeting the finesse requirements of Martha's alleged method.  It is a contrived modus operandi and a bad one.

Rather, if Martha wanted these children dead, she had the perfect opportunity to be shed of four out of the five living under her roof, all at one time.  All she had to do was nothing. Martha could have simply stood by and watched them die of the diphtheria.  Diphtheria does cause the tissues of the throat to swell, obstructing breathing.  If Martha wanted to put up a pretense of doing something prophylactic she could have mixed up a batch of sugar-water, swabbed their throats, and told them it would help.  They'd die anyway.

Instead, she nursed them.  The swabbing with hydrochloric acid was not unusual or unique.  It was a commonly prescribed home remedy of the day, used as an anti-septic and as a treatment for diphtheria's swollen throat problems.  Martha's or Thomas' purchase of any measure of the substance (as the whole city was under siege) makes perfect sense, as does the fact she made no more purchases after Arthur died.  The coroner's inquiry made much of this but it was academic.  Why would she keep buying something she no longer needed? If she was poisoning the children, and they died, then she was done and no longer needed the solution.  If she was using it as an anti-septic, and the children died, she would likewise no longer need to buy more spirits. [Uses of volatile acids in medicine in the past are not that unusual.  Germane to Martha's case was a criminal complaint levied against a Tasmanian doctor in 1847.  He applied sulfuric acid to a patient to cure a cancer (an accepted treatment) who later died.  The doctor, however, was convicted of manslaughter and jailed for eighteen months. Martha was not given the benefit of a negligence doubt].

The Morris children had a terrible time with the diphtheria.  Annie relapsed quickly enough and was back in bed with convulsions, vomiting, and diarrhea.  Dr. Cuthbert came and saw her.  He administered an anti-toxin and left Martha instructions to give small doses of laudanum (a liquid preparation containing alcohol and opium) to ease Annie's pain. When Annie died in July 1907 Cuthbert wrote out her cause of death as "epilepsy and cardiac weakness".  These conditions (not the generic "diphtheria" cause of death) are symptomatic of diphtheria.  One is the high fever which can cause convulsions ("epilepsy"), and the other is the bacterial toxins that, when released into the body, damage the heart and lead to heart failure ("cardiac weakness").  Cuthbert's cause of death listings are medically sound and based on good observations. This is not murder.

In August 1907 the other three younger children (all having recovered from, but weakened by, their bout with diphtheria) came down with typhoid.  This time Olive did not recover.  Her vomiting, diarrhea, and an undiagnosed membranous condition in her throat were present in October 1907 when she died, and her cause of death is recorded on her death certificate as "hemorrhage and typhoid" [also not diphtheria as popularly believed].



In June 1908 Arthur developed the same typhoid symptoms Olive displayed before she died (vomiting, diarrhea and the throat infection) and he died in October 6, 1908.  It was on this occasion the doctor thought something might be just a bit too coincidental in the children's deaths, and the autopsy was requested on Arthur.

As noted, Martha gave permission and attended the operation.  However, at a particular point in the autopsy she called a halt to the procedure.  This would not stand up well in court later. The prosecution felt she stopped the autopsy so her murderous poisoning wouldn't be uncovered (the team had not gotten to the throat yet). According to Martha, she stopped the autopsy because she thought the team had done enough carving to get what they needed.  Results based on the partial autopsy, however, showed an ulceration of the bowels, hemorrhage, and cardiac failure as the cause of death (all conditions caused by typhoid and a weakened heart from Arthur's earlier diphtheria).  The autopsy team made no special notes about the fact that three grown children had died within the space of fifteen months in the same household; apparently, it wasn't considered relevant.

The testimony that doctors found "traces" of hydrochloric acid in the dead children's throats is patently false.  It has to be a fabrication that went unchallenged by the defense.  Hydrochloric acid is a water soluble solution.  The concentrations Martha would have been swabbing the children's throats with would have been very mild.  It is not known from available records if the children were embalmed before burial (unlikely that the Morris clan could have afforded the cost at the time).  Even if embalmed, there would be no trace of the acid itself.  If the tissues had not decomposed to the point of uselessness (and after two years' decomposition Annie's certainly were) no doctor or scientist could detect the presence of hydrochloric acid in the throats of any of those children in 1909.  At best they might be able to see evidence of slight acid-burn scarring, and that would be expected if Martha was using the spirits of salts on their throats as she claimed she was.  So the exhumation of the bodies produced nothing but more sensationalism.

The doctors who were called to testify were found blameless in the matter.  The defense called into question their own clear negligence in treating the children, but in the wake of the Alice Mitchell "baby farm" murder trial doctors were seemingly untouchable as negligent contributors to anything.  They were above consideration as parties to the Morris children's deaths.  Martha's defense tried, however, and did ask a few relevant and probative questions on cross about the diagnoses of the children when they had diphtheria and typhoid.  He also called into the question the lack of concern, enough to report to higher authorities, anyway, when the boy Arthur died and was autopsied.  Certainly, someone was suspicious enough for that, yet no further action was taken. 

On the subject of medical ability and forensics in this case both leave a lot to be desired.  At the inquest much was made of the inability to determine just how, exactly, a person's throat constricted with repeated applications of hydrochloric acid would seem.  To help resolve this issue at trial a series of tests were done on guinea pigs and rabbits.  They suffered horribly, and their throats were indeed scarred.  But that only proves someone is capable of using an acid solution on a lab animal.  Rabbits are not humans.  Nor did anyone have any idea what concentration of the solution was allegedly used on the children.

Forensic analyses produced no evidence of poisoning with hydrochloric acid.  Nor did any forensics witnesses know of any other cases where hydrochloric acid was used as a murder weapon.  When the defense raised questions about the swabbing of the rabbits and guinea pigs with acid not producing real, practical results, there was basically a stammering of sorts: the conclusion was Martha was so conniving as a criminal mastermind that her technique could not be properly duplicated. 

Martha's defense was allowed one day in court to put on its case. Looking for information about injured at work attorney? these injured at work attorney reviews will give you some good insights.As Thomas was charged alongside her it is odd that no witnesses for character could be produced for either.  Thomas Morris was saved from the noose by the court's paradoxical belief that his son could lie about his own father, knowing the consequences [It was his son George who accused him of being Martha's accomplice and got him arrested in the first place.]  This meant they did not believe the boy's testimony.  Thus, it could be said by extrapolation that what he said should also have been disbelieved when it came to Martha's "involvement" as well.

Unfortunately, women were both weaker and stronger in this jury's mind.  Thomas Morris was acquitted because they couldn't believe his son and because they felt Martha was dominant in their relationship.  He couldn't have done it; he was too weak-willed. Thomas' frequent working away from home had an advantage of presenting him with a quick alibi, however; the jury just didn't think he had enough time to orchestrate the elaborations needed to kill the children as the prosecution described. 

That left only Martha in the hot seat.  She took much abuse publicly, and in front of her all-male jury and a gallery filled with hostile females the presiding justice called Martha a "moral deformity" (in today's courts this would call for an immediate mistrial and sanctions).  The jury found Thomas Morris not guilty, and he was free.  Martha, as expected, was quickly found guilty of the willful murder of Arthur Morris (which carried an automatic death sentence).  The jury made no recommendation for mercy.  Nor had her attorney raised the question of insanity as a possible defense.  Martha's only hope for survival was for new facts to be raised for a new trial.  Failing that, she could only pray for a commutation of her death sentence.

Thirty-eight years had passed since the last woman was hanged in Western Australia.  There was much public debate about Martha's fate.  Hardly anyone thought she was innocent of the crime, but

many felt hanging was too extreme for the circumstances.  Public opinion in some cases tried to give her the benefit of the doubt: maybe she had killed the children accidentally, etc.

The death sentence debate over Martha split neatly along class lines in Perth.  The upper class conservatives who ran the government (and whose lifestyle the likes of Martha Rendell flouted with her "easy living" in sin) continued to support capital punishment.  Others opposed hanging, especially of women.  The medical profession whose reputation was called into question and whose negligence was neatly quashed in court (in both this case and in the "baby farm" murder in 1907) stood on the side of capital punishment for Martha.  Women's groups were quiet on the subject in Western Australia (although they had protested strongly in Victoria and New South Wales in the 1890s to save two women from hanging, claiming that hanging of women by a body of men was "a barbarous act").

"There's No Place Like Home"

Popular belief is that Martha tried to poison George with a cup of tea in 1909 and she was immediately arrested.  This is not true.  In May 1909 the two older boys, George and the unnamed son, were reunited with their real mother (several months before Martha was accused of murder).  George (having not seen his real mother in three years) in the wake of this reunion ran away to live with her.  Thomas Morris did not know where the boy was, and he raised the alarm thinking something happened to him.  It was he who called in the police.

Once George (it is unclear just how long he was "missing") was found he gave police an earful about horrible Martha.  He said she had murdered his brother Arthur.  He also said Arthur had told him she was painting his throat with spirits of salt [She was. This is an indisputable fact. It was part of the boy's treatment protocol].  George whined she had served him cups of bitter tea that caused him to run away for fear of his life.  He also implicated his own father as Martha's murder accomplice.  Finally, George spilled the beans about Martha's and Thomas' "immoral" relationship.  Martha responded, unfortunately, with stupefying silence on all issues.  She only spoke of anything about her life with Thomas publicly at the later coroner's inquest and from prison (proclaiming her innocence).

Pre-trial publicity bordered on hysteria.  The crimes of which Martha Rendell was accused were horrific.  Incensed crowds of Perth women, their moral outrage unconstrained at this hussy in their midst, demanded her hanging (and worse).  The Morris home was opened up to auction off what little Thomas and Martha had to help pay for a defense.   Groups of people looted the place for souvenirs and left the accused with only enough material goods to earn £10 of auction proceeds.  

There was Martha in the middle of this circus, accused of multiple killings.  Women child murderers are the most hated, yet female killers in general have a certain allure.  They fascinate at the same time they are found repugnant.  And they make for great press.  The inspector Harry Mann's alleged statement about Martha's deriving sexual satisfaction from watching her stepchildren suffer (one that, if he made it, he was in absolutely no position to make, since he could have no way of knowing what gave Martha Rendell "sexual satisfaction") is probably a paraphrase of what the Peeping Tom neighbor said (and voyeurism was just as frowned upon then as now; why that neighbor was not called out for his own ill-mannered behavior is beyond reckoning.  He mentioned he looked in the Morris' windows "often").  Regardless, the press relished Mann's sordid little detail.  

Male felons hardly ever arouse the sort of lurid obsession in the populace that women do.  Because Martha was a "false wife" the outrage was even greater.  There were also discussions publicly about why she, in the roughly 14 years of being with Thomas Morris, did not have any children by him.  They were both obviously fertile (she had three children of her own, and Morris proved himself capable of spawning at least nine times).  The insinuations, of course were: 1) they were practicing birth control (very bad morally), or 2) Martha had aborted (even worse).

A harbinger case would have echoes in Martha's trial outcome.  In 1903 Florence MacDonald (of Queensland) was found guilty (along with her husband) of the murder of her young stepdaughter. The couple had worked, beaten, and starved the girl to death.  There was public sentiment heavily in favor of execution for the pair.  Their sentences, however, were commuted to life (the husband had well-placed friends). The Perth news reported on this case heavily as it was sensational.  

Martha, in the public's mind, was not sympathetic. She was plain, middling in years, stone-faced.  She epitomized the popular stereotype of a murdering stepmother like Florence MacDonald.  Martha had the misfortune of being a stepmother and not a "real" mother to the Morris children (and, technically, she wasn't even their "stepmother" as she and Thomas were not married).  In popular culture there was the figure of the wicked stepmother, aging, ugly, vain and haughty, and murderous of little children left in her care.  The Aussies also had a saying, "Providence is a cruel stepmother."  Stepmothers were bad.  The press reported frequently upon murders in step-families. Being the evil stepmother, combined with her stubborn silence (which she resolutely maintained for most of her time under scrutiny, though it was her legal right as a defendant in Australia) only confirmed her guilt to the jury. 

Martha was punished for being "immoral".  As a prime example of Perth's condemnation of "immorality", in 1903 three French prostitutes, in the company of three johns, were sentenced to death for their part in a fight that led to a murderous shooting in Perth. The townspeople of Perth were also suspicious of new arrivals.  A letter to the editor in the West Australian newspaper, opining on what should happen to the prostitutes, suggested "hang them all, they are all foreigners".  The jury in this case recommended mercy for these prostitutes and they were eventually freed.  Martha got no such consideration, and she was not even a prostitute.  [Only the shooter in the 1903 case was convicted]. 

The wheels of justice and retribution spun quickly in Western Australia.  Martha was hanged only twenty days after her verdict was handed down (this was also only a mere seven weeks after the coroner's inquiry, in August 1909, determined she should go to trial; her trial started in mid-September 1909). She holds the dubious

distinctions of being the third woman hanged in Western Australia, the only one executed for child murder, and the only woman ever hanged in Fremantle Prison.

Sadly, as echoed in our own times, the jury then could not tell bad "science" from the real thing and were actually enthralled by the parade of "science" that was presented to them. It is easy to overlook them since it was, after all, 1909; the science of criminal forensics was in its infancy.  However, the British Crown had already established very good guidelines for use of such evidence in cases like this one, and the lab work and medical work in this case came nowhere near that standard.

In the end, Martha was executed for being Martha. Her case was based on conjecture, supposition, and the word of a disgruntled 15 year-old-boy who wanted his mommy. The real one.

Miscellany

Not many photographs of Martha Rendell exist.  In fact, the most popular image of her is a newspaper rendering (much schedule an appointment flattering than reality) of her intake photo.  Another black and white

photograph of what purports to be Martha Rendell in 1909 was located, however, but despite its inclusion on an "authoritative" Web-site it is almost certain this picture is not of Martha Rendell.  It is probably some other woman of the era who was similarly in Fremantle Prison around the same time (maybe even Alice Mitchell, it isn't certain).  Casual inspection of the questionable picture against the one known as Martha yields much contradictory information immediately: the questionable woman has a cleft chin, dark eyes, dark hair, and her right ear is bat-like. Martha's hair is lighter as are her eyes, she is more robust than this other woman, and she has no cleft in her chin.  Furthermore, the center line of Martha's nose in profile is hooked; the unknown's is straight and upturned at the tip.  The chins are different.  Unless Martha underwent a rather quick physiological change (hair, eyes, cleft chin, major weight loss, ear cosmetic surgery to make it look worse) this isn't Martha Rendell.  But, as always, the decision about what is true and is not needs be borne by the viewer.

 

A final "viewer participation" activity concerns the reported "sightings" of an image in one of the Fremantle Prison windows resembling Martha Rendell.  The legend tells the image watches over the prison.  The saccharine sentiment behind this is absurd - Martha would no more care about watching over that prison than any other prisoner would.  She'd probably just as soon see it burned to the ground.  The "illusion" (a very vague one, requiring much in the way of stretching the imagination) can actually only be seen from the outside of the glass - looking through it from within produces no image.   This phenomenon (morphing the amorphous into recognizable shapes in the mind's eye) is called "pareidolia", and in over a dozen photos examined of this alleged phenomenon for this article none are any better or clearer than the one shown here, and this, frankly, leaves a lot to the imagination about "The Face in the Window". 

 ***

Author's Note: A "thank you" is extended to fellow InfoBarrel writer, JudyE.  Without her two excellent (entertaining and informative) articles on the Fremantle Cemetery in Western Australia, I would never have known of Martha Rendell.  Both are well worth the read (they profile some other notorious Strine criminals, Aussie oddballs, and genuine celebrities): 

Another falsely-accused Aussie sheilaLindy "the dingo ate my baby" Chamberlain

http://www.infobarrel.com/The_Evil_Stepmother

2015PreventingDrunkDriving

Healthcare worker infected dozens of hospital patients with Hepatitis C - National Law Enforcement

A New Hampshire healthcare worker pled guilty to diverting and obtaining the controlled substance fentanyl as well as to product tampering. Because of his actions, at least 45 people became infected with Hepatitis C, a virus that linked to cancer of the liver, liver damage and liver failure. One of the infected patients died from the Hepatitis C infection, according to a special report from the Federal Bureau of Investigation on Friday.

David M. Kwiatkowski, a former healthcare worker at Exeter Hospital in New Hampshire, was sentenced to 39 years in federal prison for his actions that led to a widespread Hepatitis C outbreak in various states, according to U.S. Attorneys in New Hampshire and Kansas. In addition to his 39-year sentence, the defendant will be supervised for three years following his release from prison. He also must pay a $1,600 special assessment and restitution in the amount of nearly $25,000.

After working as a health care technician at several medical facilities in Michigan between 2003 and 2007, the 34-year-old defendant became a "traveling" radiology technician, using various placement agencies to find employment at medical facilities in New York, Pennsylvania, Maryland, Arizona, Kansas, Georgia, and New Hampshire.

While employed at hospitals, he stole syringes containing Fentanyl -- a powerful narcotic that's used as an anesthetic to which he did not have authorized access -- intended for patients undergoing certain medical procedures. He replaced the stolen syringes of Fentanyl with syringes that he stole from previous procedures and refilled them with saline, after having injected himself with the Fentanyl intended for his patients.

Kwiatkowski perpetrated the http://www.constitution.org/cons/constitu.htm drug diversion and tampering despite knowing that he had tested positive for Hepatitis C, a blood-borne virus that can cause serious damage to the liver, as well as other complications.

According to the FBI, Kwiatkowski told an interrogator, "I'm going to kill a lot of people out of this."

How he contracted the virus remains a mystery, but he learned sometime in June 2010, while employed at Hays Medical Center in Kansas, that he was infected with Hepatitis C.

Despite that knowledge, he continued to inject himself using stolen Fentanyl syringes, in the process causing the contamination of the syringes with his infected blood. Looking for information about ? these 2015 workers compensation attorney reviews will give you some good insights.He refilled those tainted syringes with saline pro death penalty statistics replaced them for use on unsuspecting patients undergoing subsequent procedures. Consequently, instead of receiving their prescribed doses of Fentanyl with the intended anesthetic effect, those patients actually received saline tainted with the defendant's strain of the Hepatitis C virus.

As a "traveler," Kwiatkowski worked in no fewer than eight states, and he engaged in this diversion and tampering in each of them. His criminal activity was discovered when several unexplained cases of Hepatitis C were detected at Exeter Hospital in New Hampshire in May 2012.

The shocking discovery triggered a massive public health investigation in which authorities right to jury trial in civil cases New Hampshire, other states in which the defendant had been employed, and the Centers for Disease Control and Prevention (CDC), sought to identify the scope of the defendant's criminal conduct.



All told, the CDC investigation resulted in a recommendation that upwards of 12,000 patients should undergo testing to ascertain whether or not Kwiatkowski infected them with the virus. Testing to date has revealed that 32 patients who were treated at Exeter Hospital, six patients who were treated at Hays Medical Center in Kansas, six patients who were treated at Johns Hopkins Hospital in Maryland, and one patient who was treated at the VA Medical Center in Baltimore, Maryland, carry a strain of Hepatitis C that has been genetically linked to defendant's infection.

Besides hospital patients, an unsuspecting individual who has an intimate relationship with one of the Exeter Hospital victims also was infected with the same strain of the virus. Additionally, Hepatitis C contracted from the defendant has been identified as a contributing factor in the death of an elderly Kansas patient.

The defendant's 39-year sentence was imposed on his pleas of guilty to eight counts of obtaining controlled substances by fraud and eight counts of tampering with a consumer product. Fourteen of those charges were initiated in New Hampshire and two charges were transferred from the District of Kansas. This sentence is believed to be the highest sentence ever received for a crime of this nature.

Special Agent in Charge Vincent Lisi, of the FBI Boston Field Division said, "This was a heinous crime that touched so many of us in New Hampshire and in several states throughout the country. When you go into a hospital for treatment, you should be able to trust that someone like David Kwiatkowski will not steal pain medication intended for you and infect you with a deadly disease."

"Most of all, we are deeply thankful to the numerous victims who selflessly shared their time and extremely personal information with investigators under such difficult circumstances. They are the true heroes in this investigation. Though faced with difficult circumstances themselves, their extraordinary cooperation and information was the backbone for the investigation," SAIC Lisa.

http://www.examiner.com/article/healthcare-worker-infected-dozens-of-hospital-patients-with-hepatitis-c

2015PreventingDrunkDriving

L'Oréal heiress Liliane Bettencourt loses control of her fortune - Europe - World

The court ruling follows a long family quarrel and legal battle between Ms Bettencourt, 89 this week, and her only daughter, Françoise Bettencourt-Meyers. The two-year dispute has already spawned a series of lurid judicial and political scandals that have embarrassed President Nicolas Sarkozy.

Ms Bettencourt, whose fortune is estimated to be about EUR18bn, told a newspaper earlier this month that she would rather die or "go and live abroad" than be placed under the "suffocating" care of her daughter. A court in the Paris suburbs nevertheless decided yesterday that Ms Bettencourt was suffering from a form of Alzheimer's disease how many years is a life sentence without parole could no longer manage her own affairs. She was made a ward of her eldest grandson, Jean-Victor Meyers, 25, and her fortune, including a majority interest in the cosmetics giant L'Oréal, was placed under the control of her daughter and two grandsons. Looking for information about lawyer in las vegas? these lawyer in las vegas reviews will give you some good insights.Ms Bettencourt's lawyers said they would appeal against what they described as a "profoundly disappointing" ruling.

The saga began two years ago when Françoise Bettencourt-Meyers began a legal action to remove her mother from the influence of a photographer, François-Marie Banier. It emerged that Ms Bettencourt had given Mr Banier grand jury trials than EUR1bn in art works and life insurance policies.



The dispute appeared to have been resolved amicably last year when Mr Banier agreed to give back most of this and Ms Bettencourt agreed to resume friendly relations with her daughter. But the accord disintegrated. Ms Bettencourt-Meyers brought a new legal case alleging that her mother had fallen under the undesirable influence of her advisers.

The original http://kids.laws.com/preamble-of-the-constitution dispute generated a series of interlocking political and judicial scandals which have acquired a life of their own. Ms Bettencourt was bugged by her own butler, who said that he wanted to gather evidence that she was being swindled.

A lengthy transcript of her private conversations was leaked to the press. It suggested that she might have given illegal campaign funds to politicians, including the 2007 presidential campaign of Nicolas Sarkozy. The Elysée Palace has since been accused of illegally using the French internal security services to spy on journalists to try to block leaks in the Bettencourt affair. The head of the French internal security service, Bernard Squarcini, was placed under formal investigation by a judge yesterday for his alleged part in the affair.

Earlier a court cruel punishment Courbevoie, west of Paris, received a medical report which suggested that Ms Bettencourt was suffering from "dementia, a moderately severe form of Alzheimer's disease and a slow, degenerative brain condition".

In an interview with the Journal du Dimanche, Ms Bettencourt said that her "worst nightmare" would to be placed under the control of her daughter. "If that happens, I'm going abroad," she said. "If my daughter was in charge of me, I would suffocate...I would have no more desire to live."

Ms Bettencourt-Meyers' lawyers issued a statement saying the ruling would make no difference to the future of L'Oréal, amid rumours that Nestlé, a major shareholder, would seek to swallow up the company.

http://links.ezinemark.com/view/loral-heiress-liliane-bettencourt-loses-control-of-her-fortune-56d0e84fae1.html

2015PreventingDrunkDriving

UN push against North Korea on human rights moves ahead

UNITED NATIONS -- Despite intense lobbying by North Korea and its allies, a key committee of the U.N. General Assembly agreed to urge the Security Council to refer the leaders of North Korea to the International Criminal Court for prosecution for crimes against humanity and to reject an amendment that would have stripped the resolution of those provisions.

The cliff-hanger vote against the hostile amendment, proposed by Cuba, was supported by North Korea's allies: Cuba, China, Belarus, Ecuador, Venezuela, Russia, South Africa and Iran, among others. The final vote was 111 in favor of the action and 19 opposed, with 55 countries abstaining.

Elizabeth Cousens, U.S. Ambassador to the Economic and Social Council, said, "Human rights violations must stop and those responsible must be held responsible."

The European Union-Japan sponsored resolution was based on a U.N. Commission of Inquiry report, headed by retired Australian judge Michael Kirby, which earlier in what is consecutive sentencing year called for justice for "unspeakable atrocities."

It reported that 120,000 men, women and children were in the country's prison camps and said that the horror and intensity of the actions of North Korea, (known as the Democratic People's Republic of Korea, "DPRK") and its human rights record is "without parallel in the contemporary world."

The report documented state-sponsored abductions, forced labor, starvation, rape, forced abortion, infanticide, torture, and summary executions.

In a break from usual U.N. caution and diplomacy, the panel put North Korean Supreme Leader Kim Jong Un on notice that he could be held responsible.

Although the U.N. has known about grave human rights violations in North Korea for many years, the grim report by the independent commission created by the Human Rights Council details crimes committed against opponents of the North Korean regime.



In a letter published as part of of the 372-page report, Kirby wrote to Kim, "The Commission has found that systematic, widespread and gross human rights violations have been, and are being, committed by the Democratic People's Republic of Korea, its institutions and officials."

Kirby goes on to say, "Any official of the Democratic People's Republic Korea who commits, orders, solicits or aids and abets crimes against humanity incurs criminal responsibility by international law and must be held accountable under that law."

Kirby said the letter made it clear that Kim could personally be held responsible.

The Resolution calls for targeted sanctions as well as for cooperation, but the two clauses that caused the most consternation in Pyongyang were those that suggested that Kim could be held accountable in a criminal court -- a remote possibility since it would be likely that China would veto any such resolution at the Security Council.

Diplomats told CBS News that the intensity of the lobbying was unparalleled and that a high-ranking Chinese diplomat paid a personal visit to the European Union office in New York to try to have the language toned down.

"The North Korea resolution was adopted by a clear majority, which is significant considering that sentence for precede time the resolution includes an ICC referral reference for the first time in the U.N.'s human rights resolutions," South Korea's U.N. Ambassador Oh Joon told CBS News. "The fact that Cuba's amendment to take this new element out failed, reflects the willingness to bring the human rights debates in the U.N. to a new dimension, with the strengthened role of the international court."

Nine human rights groups, including Human Rights Watch, Amnesty International, Christian Solidarity Worldwide, the Committee for Human Rights in North Korea, and the Jacob Blaustein Institute for the Advancement of Human Rights, called on U.N. member countries to support the resolution and reject the tamping down of the criminal provisions.

But fearing the possibility of criminal charges, the North Koreans produced their own account entitled "Report of the DPRK Association for Human Rights Studies," denying the accounts of political prisoners and touting North Korea's democracy, freedom of speech and press and women's rights.

The North Korea report also detailed U.S. human rights practices: "Evil acts of all kinds including medieval and decadent tortures are under way in the prisons.... The U.S. and other Western countries turn a blind eye to the principles of mutual respect for sovereignty, non-interference, trust and mutual benefits."

That language, in addition to the fear of being referred to a criminal court, appeared to have brought several countries to support North Korean objections to the resolution. Cuba drafted an amendment, which would have stripped the language, and Iran wrote its own letter to members of the nonaligned countries.

In an effort to improve its image globally, North Korea launched a "charm offensive," releasing three detained Americans and saying it is open to nuclear and reunification talks.

In a private meeting at the Council on Foreign Relations, North Korean U.N. Ambassador Jang Il Hun said his country wanted the language about referral to the ICC removed, and that any chance of gestures like allowing a visit by a U.N. special investigator or the International Committee of the Red Cross would depend on the vote's outcome.

Jang telegraphed a firm message that there will be "countermeasures" and that "dialogue will go nowhere" on nuclear talks and reunification of the Koreas if the U.N. moves forward on the proposal to refer North Korea and Kim to the Court.

"All we ask is we do not want the resolution to include any mention of the http://kids.laws.com/articles-of-the-constitution referral of the leadership of our country to the international criminal justice mechanism or bringing those responsible to justice -- it's simple," Jang said.

European Union U.N. Looking for information about ? life in prison with parole 2015 attorney bar association reviews will give you some good insights.spokesman Christopher Matthews told CBS News, "The resolution is informed by the findings and recommendations of the landmark report, which underlined the culture of impunity and lack of accountability for the perpetrators of human rights violations in the DPRK. Accordingly, this resolution, supported by the international community, encourages the U.N. Security Council to take appropriate action to ensure accountability."

"We will be watching to see what happens next," said a Western diplomat who supported the resolution. "They said countermeasures, so expect some response."

© 2014 CBS Interactive Inc. All Rights Reserved.

a href='http://www.cbsnews.com/news/un-push-against-north-korea-on-human-rights-moves-ahead/'>http://www.cbsnews.com/news/un-push-against-north-korea-on-human-rights-moves-ahead/

2015PreventingDrunkDriving

California State Agencies Promote Safety Message for Holidays

SACRAMENTO, Calif.--(BUSINESS WIRE)--Five California State Departments are coordinating efforts during mock jury trial

holiday season to save lives along the state's

roadways, with a particular emphasis on preventing drunk driving.

Driving under the influence is a serious problem throughout California.

Last year 1,594 people were killed in alcohol-related crashes and more

than 30,000 were injured.

On Wednesday, California will begin the "maximum enforcement" period of

its efforts against drunk driving, with a five-department commitment

from the Business, Transportation and Housing Agency. Looking for information about i accident lawyer? these i accident lawyer reviews will give you some good insights.The California

Highway Patrol (CHP), Office of Traffic Safety (OTS), Department of

Alcoholic Beverage Control (ABC), Department of Motor Vehicles (DMV) and

Department of Transportation (Caltrans), each have specific

responsibilities that contribute to the success of the state's

anti-drunk driving effort.

Between 6 p.m. Wednesday, November 21 and midnight, Sunday November 25,

the CHP will implement a Maximum Enforcement Period (MEP). "During

this time, up to 80 percent of our officers will be working so your

family can safely arrive at and enjoy holiday celebrations,"

Commissioner Mike Brown said. "For those who

do not obey https://www.law.cornell.edu/constitution/preamble what is legal punishment law, not only will our officers be out in force, but

we've also enlisted the help of the public to dial 911 to report drunk

drivers."

the state Office of Traffic Safety Director believes wearing a safety

belt is the single most effective thing motorists can do to save lives

and reduce injuries on California's roadways. "Two

seconds is all it takes to buckle a seat belt. That could be the

difference between life and death in a crash,"

said Christopher J. Murphy, Director of the state Office of Traffic

Safety.

life without the possibility of parole addition to adults, parents and guardians need to make sure their

younger children are in properly attached safety and booster seats and

those six and over are buckled up as well.

Other efforts include safety tips that will be displayed on Caltrans

message boards throughout California. "Caltrans

will remind motorists how important it is to practice safe driving

habits during the entire holiday season,"

said Caltrans Director Will Kempton.

California Alcoholic Beverage Control (ABC) investigators will be

working in communities to ensure that licensed businesses are complying

with the law. "Thanksgiving is a time for

families and friends to get together and we want to do our part to

ensure it is a safe holiday period," said ABC

Director Steve Hardy.

That sentiment is echoed by DMV Director George Valverde. "The

DMV will take prompt action against the driver's

license of any motorist who is cited for driving under the influence of

alcohol or drugs," said DMV Director George

Valverde. "Driver safety is one of our top

concerns, especially during periods of high holiday traffic."

DMV will be displaying safety messages in several right to a jury trial in civil cases href="http://lawyercertification2015.snack.ws/atrazine-lawsuits-still-a-battle-in-illinois-by-sue-schulte.html">of its 169 field

offices throughout California.



a href='http://www.businesswire.com/news/home/20071121005607/en/California-State-Agencies-Promote-Safety-Message-Holidays'>http://www.businesswire.com/news/home/20071121005607/en/California-State-Agencies-Promote-Safety-Message-Holidays

2015PreventingDrunkDriving

In Pivotal Phase III Studies, Merck’s Investigational Medicine Boceprevir Helped Majority of Patients with Chronic Hepatitis C Genotype 1 Infection Achieve Sustained Virologic Response, the Primary Endpoint of the Studies

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck today reported that two pivotal Phase III registration studies for

boceprevir, its investigational oral hepatitis C protease inhibitor,

have been completed and met the primary endpoints: in both studies in

patients with chronic hepatitis C virus (HCV) genotype 1 infection, the

addition of boceprevir to treatment with PEGINTRON®

(peginterferon alfa-2b) and REBETOL® (ribavirin, USP)

(Peg/riba) significantly increased the number of patients who achieved

sustained virologic response (SVR; defined as undetectable virus levels

24 weeks after the end of treatment), compared to control groups that

received Peg/riba plus placebo.

Boceprevir, in combination with Peg/riba, is being studied for the

treatment of patients with chronic hepatitis C genotype I who have

previously been treated (treatment-failure; HCV RESPOND-2) grand jury trial in

patients who are new to treatment (treatment-naïve; HCV SPRINT-2).

Abstracts for boceprevir studies have already been submitted for

presentation at a medical meeting later this year, and additional

abstracts are being submitted this week. Merck plans to submit a New

Drug Application (NDA) for boceprevir to the U.S. Food and Drug

Administration on a rolling basis, and expects to complete regulatory

submissions in the U. S. and E.U. in 2010.

"There is a clear need for new treatment strategies for chronic

hepatitis C," said Dr. Peter S. Kim, Ph.D., president, Merck Research

Laboratories. "We look forward to seeking regulatory approvals to bring

boceprevir forward to help treat people living with chronic hepatitis C."

The HCV RESPOND-2 and HCV SPRINT-2 studies each evaluated two treatment

strategies with boceprevir: 48 weeks of treatment for all patients

(4-week lead-in with 1.5 mcg/kg/week of PEGINTRON and an investigational

dose of 600-1,400 mg/day of REBETOL, followed by the addition of

boceprevir 800 mg three times a day for 44 weeks), and response-guided

therapy, in which patients with undetectable virus at week 8 and again

at certain points later in the studies were able to stop all treatment

at 36 weeks in HCV RESPOND-2 and at 28 weeks in HCV SPRINT-2. Patients

who did not meet these criteria continued treatment with Peg/riba alone

for a total treatment duration of 48 weeks. Control groups in the

studies received Peg/riba at the doses described above plus placebo for

48 weeks.

The HCV RESPOND-2 study was conducted in 403 patients who failed prior

therapy at U.S. and international sites, and patients were randomized

into the three groups (48 weeks control; 48 weeks control plus

boceprevir; control plus boceprevir using response-guided therapy) at a

1:1:1 ratio. In the boceprevir 48-week treatment group, 66 percent of

patients achieved SVR, and in the boceprevir response-guided therapy

group, 59 percent of patients achieved SVR, compared to 21 percent of

patients in the control group (p<0.0001 for both, intent-to-treat

analysis).

"These results are very exciting," said Bruce R. Bacon, M.D., professor

of internal medicine, Saint Louis University School of Medicine, and

co-principal investigator of the HCV RESPOND-2 study. "Patients who

failed prior hepatitis C therapy are among the hardest to treat, and the

use of boceprevir in this study helped significantly more of these

patients achieve undetectable levels of the virus at 24 weeks after the

end of therapy than treatment with Peg/riba alone."

In the HCV SPRINT-2 study, 1,097 treatment-naïve patients at U.S. and

international sites were enrolled in two separate cohorts, one with 938

non-African-American/Black patients and the other with 159

African-American/Black patients. Patients were randomized into the three

treatment groups (48 weeks control; 48 weeks control plus boceprevir;

control plus boceprevir using response-guided therapy) at a ratio of

1:2:2. In the study overall, 66 percent of patients in the boceprevir

48-week treatment group achieved SVR, and 63 percent of patients in the

response-guided therapy group achieved SVR, compared to 38 percent of

patients in the control group (p<0.0001 for both, intent-to-treat

analysis).

As specified by the HCV SPRINT-2 study protocol, results for the

non-African-American/Black and African-American/Black patient cohorts

were analyzed separately. Several previous studies have shown that

African-American/Black patients have a lower response to HCV treatment

than non-African-American/Black patients.1-3 Among the

non-African-American/Black patients in the boceprevir 48-week treatment

group, 69 percent achieved SVR, and in the response-guided therapy

group, 67 percent of patients achieved SVR, compared to 40 percent in

the control group (p<0.0001 for both, intent-to-treat analysis). Among

the African-American/Black patients, 53 percent of patients in the

48-week treatment group and 42 percent of patients in the

response-guided therapy group achieved SVR, compared to 23 percent in

the control group (p=0.004 and p=0.044, respectively, intent-to-treat

analysis).

"The response-guided therapy approach used in these studies enabled

those patients - both treatment-failure patients and treatment-naïve

patients - who had undetectable virus at certain points of the study to

achieve SVR with a shorter total treatment duration than current

standard therapy," said Fred Poordad, M.D., chief of hepatology in the

division of gastroenterology at Cedars-Sinai Medical Center, associate

professor of medicine at the David Geffen School of Medicine, University

of California, Los Angeles (UCLA), and co-principal investigator of the

HCV SPRINT-2 study.

In the HCV RESPOND-2 study, the five most common treatment-emergent

adverse events reported for the boceprevir 48-week treatment group,

boceprevir response-guided therapy group and control group,

respectively, were: fatigue (57, 54, and 50 percent), headache (40, 43

and 49 percent), nausea (42, 44 and 38 percent), anemia (47, 43 and 20

percent) and dysgeusia (bad taste) (45, 43 and 11 percent). Treatment

discontinuations due to anemia were 3 percent and 0 percent for the

boceprevir groups, respectively, compared to 0 percent for the control

group. Treatment discontinuations due to adverse events overall were 12

percent and 8 percent for the boceprevir groups, respectively, compared

to 3 percent for the control group.

In the HCV SPRINT-2 study, the five most common treatment-emergent

adverse events reported for the boceprevir 48-week treatment group,

boceprevir response-guided therapy group and control group,

respectively, were: fatigue (57, 53 and 60 percent), headache (46, 46

and 42 percent), nausea (43, 48 and 42 percent), anemia (49, 49 and 29

percent) and pyrexia (fever) (32, 33 and 33 percent). Treatment

discontinuations due to anemia were 2 percent for each of the boceprevir

groups compared to 1 percent for the control group. Treatment

discontinuations due to adverse events overall were 16 percent and 12

percent for the boceprevir groups, respectively, compared to 16 percent

for the control group.

About the studies

The HCV RESPOND-2 study was conducted in patients chronically infected

with hepatitis C genotype 1 who failed prior therapy with peginterferon

and ribavirin, including those who had experienced prior relapse or who

were prior non-responders, and the HCV SPRINT-2 study was conducted in

previously untreated (treatment-naïve) patients chronically infected

with hepatitis C genotype 1. Approximately 25 percent of patients in

each of the studies had less than a 1 log decrease in viral load after

the 4-week Peg/riba lead-in period.

Sustained virologic response (SVR), the protocol-specified primary

efficacy endpoint, is defined as achievement of undetectable HCV-RNA at

24 weeks after the end of treatment in all randomized patients treated

with any study medication (Roche TaqMan LLD=9.3 IU/mL). Per protocol, if

a patient did not have a 24-week post-treatment assessment, the

patient's 12-week post-treatment assessment was utilized.

In the HCV RESPOND-2 study, patients in the response-guided therapy arm

who had undetectable virus at treatment week 8 and week 12 received a

total of 36 weeks of therapy (lead-in with Peg/riba followed by the

addition of boceprevir for 32 weeks); patients with detectable virus at

week 8, but undetectable virus at week 12, stopped boceprevir treatment

at week 36 and continued on Peg/riba alone for an additional 12 weeks,

for a total treatment duration of 48 weeks. Patients in any arm of the

study who had detectable virus at week 12 were considered treatment

failures and discontinued treatment.

In the HCV SPRINT-2 study, patients in the response-guided therapy group

of the study who had undetectable virus at treatment week 8 through week

24 received a total of 28 weeks of therapy (lead-in with Peg/riba

followed by the addition of boceprevir for 24 weeks); patients with

detectable virus at week 8, but undetectable virus at week 24, stopped

boceprevir treatment at week 28 and continued on Peg/riba alone for a

total treatment duration of 48 weeks. Patients in any arm of the study

who had detectable virus at week 24 were considered treatment failures

and discontinued treatment.

Merck's commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the hepatitis

field by continuing to discover, develop and deliver vaccines and

medicines to help prevent and treat viral hepatitis. Extensive research

efforts are underway to develop differentiated oral therapies that bring

innovation to hepatitis care.

Conference call

Investors are invited to a live webcast of Merck's conference call today

at 9:00 a.m. EDT by visiting Merck's Web site, www.merck.com/investors/events-and-presentations/home.html.

Institutional investors and analysts can participate in the call by

dialing (877) 381-5782 or (706) 758-9927. Journalists are invited to

listen in on the call by dialing (800) 399-7917 or (706) 758-9928. A

replay of the webcast will be available starting at 11 a.m. EDT today

through 5 p.m. EDT on Aug. 11. To listen to the replay, dial (800)

642-1687 or (706) 645-9291. The conference ID No. is 92380347.

About PEGINTRON

PEGINTRON is indicated for use in combination with REBETOL (ribavirin)

for the treatment of chronic hepatitis C in patients three years of age

and older with compensated liver disease.

The following points should be considered when initiating therapy with

PEGINTRON in combination with REBETOL: (1) These indications are based

on achieving undetectable HCV-RNA after treatment for 24 or 48 weeks and

maintaining a Sustained Virologic Response (SVR) 24 weeks after the last

dose. (2) Patients with the following characteristics are less likely to

benefit from re-treatment after failing a course of therapy: previous

nonresponse, previous pegylated interferon treatment, significant

bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety

and efficacy data are available for treatment of longer than one year.

PEGINTRON is also indicated for use alone for the treatment of chronic

hepatitis C in patients with compensated liver disease previously

untreated with interferon alpha and who are at least 18 years of age.

The following points should be considered when initiating therapy with

PEGINTRON alone: Combination therapy with REBETOL is preferred over

PEGINTRON monotherapy unless there are contraindications to, or

significant intolerance of, REBETOL. Combination therapy provides

substantially better response rates than monotherapy.

 

Selected Safety Information on PEGINTRON

 

WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED

EFFECTS

Alpha interferons, including PEGINTRON, may cause or aggravate

fatal or life-threatening neuropsychiatric, autoimmune, ischemic,

and infectious disorders. Patients should be monitored closely

with periodic clinical and laboratory evaluations. Patients with

persistently severe or worsening signs or symptoms of these

conditions should be withdrawn from therapy. In many, but not all

cases, these disorders resolve after stopping PEGINTRON therapy.

 

Use with Ribavirin:

Ribavirin may cause birth defects and death of the unborn child.

Extreme care must be taken to avoid pregnancy in female patients

and in female partners of male patients. Ribavirin causes

hemolytic anemia. The anemia associated with REBETOL therapy may

result in a worsening of cardiac disease. Ribavirin is genotoxic

and mutagenic and should be considered a potential carcinogen.

Contraindications

PEGINTRON is contraindicated in patients with known hypersensitivity

reactions such as urticaria, angioedema, bronchoconstriction,

anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to

interferon alpha or any other component of the product, autoimmune

hepatitis, and hepatic decompensation (Child-Pugh score greater than 6

[class B and C]) in cirrhotic CHC patients before or during treatment.

PEGINTRON/REBETOL combination therapy is additionally contraindicated in

women who are pregnant or may become pregnant, men whose female partners

are pregnant, patients with hemoglobinopathies (e.g., thalassemia major,

sickle-cell anemia), and patients with creatinine clearance less than 50

mL per min.

Pregnancy

REBETOL therapy should not be started until a report of a negative

pregnancy test has been obtained immediately prior to planned initiation

of therapy. Patients should use at least two effective forms of

contraception and have monthly pregnancy tests during therapy and for

six months after completion of therapy. If this drug is used during

pregnancy, or if a patient becomes pregnant, the patient should be

apprised of the potential hazard to a fetus. A Ribavirin Pregnancy

Registry has been established to monitor maternal-fetal outcomes of

pregnancies in female patients and female partners of male patients

exposed to ribavirin during treatment, and for six months following

cessation of treatment. Physicians and patients are encouraged to report

such cases by calling 1-800-593-2214.

Patients with the following conditions should be closely monitored

and may require dose reduction or discontinuation of therapy:

Hemolytic anemia with ribavirin

Neuropsychiatric events

History of significant or unstable cardiac disease

Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that

cannot be effectively treated by medication

New or worsening ophthalmologic disorders

Ischemic and hemorrhagic cerebrovascular events

Severe decreases in neutrophil or platelet counts

History of autoimmune disorders

Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and

pancreatitis

Pulmonary infiltrates or pulmonary function impairment

Child-Pugh score greater than 6 (Class B and C)

Increased creatinine levels in patients with renal insufficiency

Serious, acute hypersensitivity reactions and cutaneous eruptions

Dental/periodontal disorders reported with combination therapy

Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides

greater than 1000 mg/dL)

Weight loss and growth inhibition reported with combination therapy in

pediatric patients.

Life-threatening or fatal neuropsychiatric events, including suicidal

and homicidal ideation, depression, relapse of drug addiction/overdose,

and aggressive behavior, sometimes directed towards others, have

occurred in patients with and without a previous psychiatric disorder

during PEGINTRON treatment and follow-up.

Adverse events

Serious adverse reactions have occurred in approximately 12 percent of

subjects in clinical trials. The most common serious events occurring in

subjects treated with PEGINTRON and REBETOL were depression and suicidal

ideation, each occurring at a frequency of less than 1 percent. The most

common fatal events occurring in subjects treated with PEGINTRON and

REBETOL were cardiac arrest, suicidal ideation, and suicide attempt, all

occurring in less than 1 percent of subjects.

The incidence of serious adverse reactions was comparable between

PEGINTRON monotherapy (about 12 percent) and PEGINTRON/REBETOL

combination therapy weight-based (12 percent) or flat-dose (17 percent).

In many but not all cases, adverse reactions resolved after dose

reduction or discontinuation of therapy. Some patients experienced

ongoing or new serious adverse reactions during the 6-month follow-up

period. In a study with PEGINTRON/REBETOL (weight-based) combination

therapy in adult patients, anemia with weight-based dosing occurred at

an increased rate (29 percent vs. 19 percent); however, the majority of

these cases were mild and responded to dose reductions. The incidence of

serious adverse reactions reported for the weight-based REBETOL group

was 12 percent. There were 31 deaths in clinical trials which occurred

during treatment or during follow-up. Of the deaths, 19 were patients on

either PEGINTRON or PEGINTRON/REBETOL combination therapy and three

occurred during the follow-up period but had been on PEGINTRON/REBETOL

combination therapy.

Additional serious adverse reactions seen in clinical trials at a

frequency of equal to or less than 1 percent included psychosis,

aggressive reaction, relapse of drug addiction/overdose; nerve palsy

(facial, oculomotor); cardiomyopathy, angina, pericardial effusion,

retinal ischemia, retinal artery or vein thrombosis, blindness,

decreased visual acuity, optic neuritis, transient ischemic attack,

supraventricular arrhythmias, loss of consciousness; neutropenia,

infection (sepsis, pneumonia, abscess, cellulitis); emphysema,

bronchiolitis obliterans, pleural effusion, gastroenteritis,

pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism,

autoimmune thrombocytopenia with or without purpura, rheumatoid

arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis,

aggravated psoriasis, urticaria, injection site necrosis, vasculitis,

and phototoxicity.

Greater than 96 percent of all subjects in clinical trials experienced

one or more adverse events. Most common adverse reactions (greater than

40 percent) in adult patients receiving either PEGINTRON or

PEGINTRON/REBETOL are injection site inflammation/reaction,

fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and

anxiety/emotional lability/irritability.

The adverse reaction profile was similar between weight-based and

flat-dose PEGINTRON/REBETOL therapies. Weight-based PEGINTRON/REBETOL

dosing resulted in increased rates of anemia. Most common adverse

reactions with PEGINTRON/REBETOL (weight-based) therapy were

psychiatric, which occurred among 68-69 percent of patients and included

depression, irritability, and insomnia, each reported by approximately

30-40 percent of subjects in all treatment groups. Suicidal behavior

(ideation, attempts, and suicides) occurred in 2 percent of all patients

during treatment or during follow-up after treatment cessation. Other

common reactions included injection site reactions, fatigue/ asthenia,

headache, rigors, fever, nausea, myalgia, anxiety/emotional

lability/irritability. The severity of some of these systemic symptoms

tends to decrease as treatment continues.

Subjects receiving PEGINTRON/REBETOL as re-treatment after failing a

previous interferon combination regimen reported adverse reactions

similar to previous treatment-naïve patients receiving this regimen.

In general, the adverse reaction profile in the pediatric population was

similar to that observed in adults. Most common adverse reactions

(greater than 25 percent) in pediatric patients receiving

PEGINTRON/REBETOL are pyrexia, headache, neutropenia, fatigue, anorexia,

injection site erythema, abdominal pain, and vomiting.

Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.

About Merck

Today's Merck is a global healthcare leader. Merck is known as MSD

outside the United States and Canada. Through our prescription

medicines, vaccines, biologic therapies, and consumer care and animal

health products, we work with customers and operate in more than 140

countries to deliver innovative health solutions. We also demonstrate

our commitment to increasing access to healthcare through far-reaching

policies, programs and partnerships. For more information, visit www.merck.com.

Forward-Looking Statement

This news release includes "forward-looking statements" within the

meaning of the safe harbor provisions of the United States Private

Securities Litigation Reform Act of 1995. Such statements may include,

but are not limited to, statements about the benefits of the merger

between Merck and Schering-Plough, including future financial and

operating results, the combined company's plans, objectives,

expectations and intentions and other statements that are not historical

facts. Such statements are based upon the current beliefs and

expectations of Merck's management and are subject to significant risks

and uncertainties. Actual results may differ from those set forth in the

forward-looking statements.

The following factors, among others, could cause actual results to

differ from those set forth in the forward-looking statements: the

possibility that the expected synergies from the merger of Merck and

Schering-Plough will not be realized, or will not be realized within the

expected time period; the impact of pharmaceutical industry regulation

and health care legislation; the risk that the businesses will not be

integrated successfully; disruption from the merger making it more

difficult to maintain business and operational relationships; Merck's

ability to accurately predict future market conditions; dependence on

the effectiveness of Merck's patents and other protections for

innovative products; the risk of new and changing regulation and health

policies in the U.S. and internationally and the exposure to litigation

and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking

statement, whether as a result of new information, future events or

otherwise. Additional factors that could cause results to differ

materially from those described in the forward-looking statements can be

found in Merck's 2009 Annual Report on Form 10-K and the company's other

filings with the Securities and Exchange Commission (SEC) available at

the SEC's Internet site (www.sec.gov).

# # #

Please see attached Prescribing Information and Medication Guide

including Boxed Warning for PEGINTRON® and

REBETOL®. Full Prescribing Information

and Medication Guide is also available at http://www.spfiles.com/pipeg-intron.pdf.

PEGINTRON® and REBETOL®

are registered trademarks of Schering Corp., a subsidiary of Merck &

Co., Inc., Whitehouse Station, N.J., USA.

Endnotes

1 McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b

or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl

J Med 2009;361:580-93.

2 Jeffers LJ, Cassidy W, Howell CD, et al. Peginterferon Alfa-2a (40 kd)

and Ribavirin for Black American Patients With Chronic HCV Genotype 1.

Hepatology 2004;39:1702-1708.

3 Muir AJ, Bornstein JD, Killenberg, PG. Peginterferon Alfa-2b and

Ribavirin for the Treatment of Chronic Hepatitis C in Blacks and

Non-Hispanic Whites. N Engl J Med 2004;350:2265-71.

F- 33538820T

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

PegIntron safely and effectively. Looking for information about serious accident lawyers? these serious accident lawyers reviews will give you some good insights.See full prescribing

information for PegIntron.

PegIntron (Peginterferon alfa-2b) Injection, Powder for Solution for

Subcutaneous Use

Initial U.S. Approval: 2001

 

WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED

EFFECTS

See full prescribing information for complete boxed warning.

May cause or aggravate fatal or life-threatening

neuropsychiatric,

autoimmune, ischemic, and

infectious disorders. Monitor closely

and withdraw

therapy with persistently severe or worsening signs or

symptoms

of the above disorders. (5)

Use with Ribavirin

Ribavirin may cause birth defects and fetal death; avoid

pregnancy

in female patients and female partners of

male patients. (5.1)

Ribavirin is a potential carcinogen. (5.1, 13.1)

 

----------------------------RECENT MAJOR

CHANGES--------------------------

Warnings and Precautions, Endocrine Disorders (5.4)

 

 

 

[1/2010]

Warnings and Precautions, Ophthalmologic Disorders (5.5)

[8/2009]

Warnings and Precautions, Pulmonary Disorders (5.11)

[8/2009]

Warnings and Precautions, Peripheral Neuropathy (5.19)

[8/2009]

 

----------------------------INDICATIONS AND

USAGE---------------------------

PegIntron is an antiviral indicated for

Combination therapy with REBETOL

(ribavirin):

Chronic Hepatitis C (CHC) in patients >=3 years with

compensated liver disease. (1.1)

Patients with the

following characteristics are less likely to benefit from re-treatment

after failing a course of therapy: previous nonresponse, previous

pegylated interferon treatment, significant bridging fibrosis or

cirrhosis, and genotype 1 infection. (1.1)

Monotherapy: CHC in patients

(>=18 years) with compensated liver disease previously untreated with

interferon alpha. (1.1)

----------------------DOSAGE AND ADMINISTRATION-----------------------

PegIntron is administered by subcutaneous injection.

 

 

 

 

 

 

 

 

 

 

 

PegIntron

Dose

(Adults)*

 

PegIntron

Dose

(Pediatric

Patients)

 

REBETOL

Dose*

(Adults)

 

REBETOL

Dose

(Pediatric

Patients)

PegIntron/

REBETOL

Combination

Therapy (2.1)

 

1.5

mcg/kg/

week

 

60 mcg/m2/

week

 

800-1400 mg

orally daily

with food

 

15 mg/kg/day

orally with

food in 2

divided doses

* Refer to Tables 1-7 of the full Prescribing Information.

Dose reduction is recommended in patients experiencing certain adverse

reactions or renal dysfunction. (2.3, 2.5)

---------------------DOSAGE FORMS AND STRENGTHS----------------------

Single-use vial (with 1.25 mL diluent) and REDIPEN® (3):



50 mcg per 0.5 mL, 80 mcg per 0.5 mL, 120 mcg per 0.5 mL, 150 mcg per

0.5 mL.

-------------------------------CONTRAINDICATIONS------------------------------

Known hypersensitivity reactions, such as urticaria, angioedema,

bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome, and toxic

epidermal necrolysis to interferon alpha or any other product

component. (4)

Autoimmune hepatitis. (4)

Hepatic decompensation (Child-Pugh score >6 [class B and C]) in

cirrhotic CHC patients before or during treatment. (4)

Additional contraindications for combination therapy with ribavirin:

Pregnant women and men whose female partners are pregnant. (4, 8.1)

Hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia). (4)

Creatinine clearance <50 mL/min. (4)

-----------------------WARNINGS AND

PRECAUTIONS------------------------

Birth defects and fetal death with ribavirin: Patients must have a

negative pregnancy test prior to therapy, use at least 2 forms of

contraception, and undergo monthly pregnancy tests. (5.1)

Patients exhibiting the following conditions should be closely monitored

and may require dose reduction or discontinuation of therapy:

Hemolytic anemia with ribavirin. (5.1)

Neuropsychiatric events. (5.2)

History of significant or unstable cardiac disease. (5.3)

Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that

cannot be effectively treated by medication. (5.4)

New or worsening ophthalmologic disorders. (5.5)

Ischemic and hemorrhagic cerebrovascular events. (5.6)

Severe decreases in neutrophil or platelet counts. (5.7)

History of autoimmune disorders. (5.8)

Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and

pancreatitis. (5.9, 5.10)

Pulmonary infiltrates or pulmonary function impairment. (5.11)

Child-Pugh score >6 (class B and C). (4, 5.12)

Increased creatinine levels in patients with renal insufficiency (5.13)

Serious, acute hypersensitivity reactions and cutaneous eruptions

(5.14)

Dental/periodontal disorders reported with combination therapy (5.16)

Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides

>1000 mg/dL) (5.17)

Weight loss and growth inhibition reported with combination therapy in

pediatric patients (5.18)

Peripheral neuropathy when used in combination with telbivudine (5.19)

------------------------------ADVERSE

REACTIONS-------------------------------

Most common adverse reactions (>40%) in adult patients receiving either

PegIntron or PegIntron/REBETOL are injection site inflammation/reaction,

fatigue/asthenia, headache, rigors, fevers, nausea, myalgia and

anxiety/emotional lability/irritability (6.1). Most common adverse

reactions (>25%) in pediatric patients receiving PegIntron/REBETOL are

pyrexia, headache, neutropenia, fatigue, anorexia, injection-site

erythema, vomiting (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Schering Corporation

at 1-800-526-4099 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

------------------------------DRUG

INTERACTIONS-------------------------------

Drug metabolized by CYP450: Caution with drugs metabolized by CYP2C8/9

(e.g., warfarin, phenytoin) or CYP2D6 (e.g., flecainide). (7.1)

Methadone: Monitor for increased narcotic effect. (7.2)

Nucleoside analogues: Closely monitor for toxicities. Discontinue

nucleoside reverse transcriptase inhibitors or reduce dose or

discontinue interferon, ribavirin, or both with worsening toxicities.

(7.3)

Didanosine: Concurrent use with REBETOL is not recommended. (7.3)

-----------------------USE IN SPECIFIC

POPULATIONS------------------------

Ribavirin Pregnancy Registry: 1-800-593-2214 (8.1)

Pediatrics: safety and efficacy in pediatrics <3 years old have not

been established (8.4)

Geriatrics: neuropsychiatric, cardiac, pulmonary, GI, and systemic

(flu-like) adverse reactions may be more severe (8.5)

Organ transplant: safety and efficacy have not been studied (8.6)

HIV or HBV co-infection: safety and efficacy have not been established

(8.7)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 1/2010

_______________________________________________________________________________________________________________________________________

 

FULL PRESCRIBING INFORMATION: CONTENTS*

 

WARNING - RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED

EFFECTS

1 INDICATIONS AND USAGE

1.1 Chronic Hepatitis C

2 DOSAGE AND ADMINISTRATION

2.1 PegIntron/REBETOL Combination Therapy

2.2 PegIntron Monotherapy

2.3 Dose Reduction

2.4 Discontinuation of Dosing

2.5 Renal Function

2.6 Preparation and Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Use with Ribavirin

5.2 Neuropsychiatric Events

5.3 Cardiovascular Events

5.4 Endocrine Disorders

5.5 Ophthalmologic Disorders

5.6 Cerebrovascular Disorders

5.7 Bone Marrow Toxicity

5.8 Autoimmune Disorders

5.9 Pancreatitis

5.10 Colitis

5.11 Pulmonary Disorders

5.12 Hepatic Failure

5.13 Patients with Renal Insufficiency

5.14 Hypersensitivity

5.15 Laboratory Tests

5.16 Dental and Periodontal Disorders

5.17 Triglycerides

5.18 Impact on Growth- Pediatric Use

5.19 Peripheral Neuropathy

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Immunogenicity

6.3 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Drugs Metabolized by Cytochrome P-450

7.2 Methadone

7.3 Use with Ribavirin (Nucleoside Analogues)

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Organ Transplant Recipients

8.7 HIV or HBV Coinfection

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Chronic Hepatitis C in Adults

14.2 Chronic Hepatitis C in Pediatrics

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

17.1 Medication Guide

17.2 Pregnancy

17.3 HCV Transmission

17.4 Laboratory Evaluations, Hydration, "Flu-like" Symptoms

*Sections or subsections omitted from the full prescribing

information are not listed.

_______________________________________________________________________________________________________________________________________

FULL PRESCRIBING INFORMATION

WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS

Alpha interferons, including PegIntron, may cause or aggravate fatal

or life-threatening neuropsychiatric, autoimmune, ischemic, and

infectious disorders. Patients should be monitored closely with

periodic clinical and laboratory evaluations. Patients with

persistently severe or worsening signs or symptoms of these conditions

should be withdrawn from therapy. In many, but not all cases,

these disorders resolve after stopping PegIntron therapy [see

Warnings and Precautions (5) and Adverse Reactions

(6.1)].

Use with Ribavirin

Ribavirin may cause birth defects and death of the unborn child. Extreme

care must be taken to avoid pregnancy in female patients and in female

partners of male patients. Ribavirin causes hemolytic anemia. The

anemia associated with REBETOL therapy may result in a worsening of

cardiac disease. Ribavirin is genotoxic and mutagenic and should

be considered a potential carcinogen. [See REBETOL package

insert]

1 INDICATIONS AND USAGE

1.1 Chronic Hepatitis C

Combination therapy:

PegIntron® in combination with REBETOL® (ribavirin) is indicated for the

treatment of chronic hepatitis C in patients 3 years of age and older

with compensated liver disease.

The following points should be considered when initiating therapy with

PegIntron in combination with REBETOL:

These indications are based on achieving undetectable HCV-RNA after

treatment for 24 or 48 weeks and maintaining a Sustained Virologic

Response (SVR) 24 weeks after the last dose.

Patients with the following characteristics are less likely to benefit

from retreatment after failing a course of therapy: previous

nonresponse, previous pegylated interferon treatment, significant

bridging fibrosis or cirrhosis, and genotype 1 infection [see

Clinical Studies (14)].

No safety and efficacy data are available for treatment of longer than

1 year.

Monotherapy (for patients who are

intolerant to ribavirin):

PegIntron (peginterferon alfa-2b) is indicated for use alone for the

treatment of chronic hepatitis C in patients with compensated liver

disease previously untreated with interferon alpha and who are at least

18 years of age.

The following point should be considered when initiating therapy with

PegIntron alone:

Combination therapy with REBETOL is preferred over PegIntron

monotherapy unless there are contraindications to or significant

intolerance of REBETOL.

Combination therapy provides

substantially better response rates than monotherapy [see Clinical

Studies (14)].

2 DOSAGE AND ADMINISTRATION

2. 1 PegIntron/REBETOL Combination Therapy

REBETOL should be taken with food. REBETOL should not be used in

patients with creatinine clearance <50 mL/min.

Adults

The recommended dose of PegIntron is 1.5 mcg/kg/week subcutaneously in

combination with 800 to 1400 mg of REBETOL orally based on patient body

weight. The volume of PegIntron to be injected depends on the strength

of PegIntron and patient's body weight (see Table 1).

Duration of Treatment - Interferon Alpha-naïve Patients

The treatment duration for patients with genotype 1 is 48 weeks.

Discontinuation of therapy should be considered in patients who do not

achieve at least a 2 log10 drop or loss of HCV-RNA at 12

weeks, or if HCV-RNA remains detectable after 24 weeks of therapy.

Patients with genotype 2 and 3 should be treated for 24 weeks.

Duration of Treatment - Re-treatment with PegIntron/REBETOL of Prior

Treatment Failures

The treatment duration for patients who previously failed therapy is 48

weeks, regardless of HCV genotype. Re-treated patients who fail to

achieve undetectable HCV-RNA at Week 12 of therapy, or whose HCV-RNA

remains detectable after 24 weeks of therapy, are highly unlikely to

achieve SVR and discontinuation of therapy should be considered [see

Clinical Studies (14.1)].

TABLE 1

Recommended PegIntron Combination Therapy Dosing (Adults)

Body weight

kg (lbs)

 

PegIntron

REDIPEN® or Vial

Strength to Use

 

Amount of

PegIntron

(mcg) to

Administer

 

Volume (mL)*

of PegIntron to

Administer

 

REBETOL

Daily Dose

 

REBETOL Number of

Capsules

<40

(<88)

 

50 mcg per 0.5 mL

 

50

 

0.5

 

800 mg/day

 

2 x 200 mg capsules A.M.

2 x 200 mg capsules P.M.

40 - 50

(88 - 111)

 

80 mcg per 0.5 mL

 

64

 

0.4

 

800 mg/day

 

2 x 200 mg capsules A.M.

2 x 200 mg capsules P.M.

51 - 60

(112 - 133)

 

 

80

 

0.5

 

800 mg/day

 

2 x 200 mg capsules A.M.

2 x 200 mg capsules P.M.

61 - 65

(134 - 144)

120 mcg per 0.5 mL

96

 

0.4

 

800 mg/day

 

2 x 200 mg capsules A.M.

2 x 200 mg capsules P.M.

66 - 75

(145 - 166)

96

 

0.4

 

1000 mg/day

 

2 x 200 mg capsules A.M.

3 x 200 mg capsules P.M.

76 - 80

(167 - 177)

120

 

0.5

 

1000 mg/day

 

2 x 200 mg capsules A.M.

3 x 200 mg capsules P.M.

81 - 85

(178 - 187)

 

 

 

 

1200 mg/day

 

3 x 200 mg capsules A.M.

3 x 200 mg capsules P.M.

86 - 105

(188 - 231)

 

150 mcg per 0.5 mL

 

150

 

0.5

 

1200 mg/day

 

3 x 200 mg capsules A.M.

3 x 200 mg capsules P.M.

>105

(>231)

 

**

 

**

 

**

 

1400 mg/day

 

3 x 200 mg capsules A.M.

4 x 200 mg capsules P.M.

* When reconstituted as directed.

** For patients weighing >105 kg (>231 pounds), the PegIntron dose

of 1.5 mcg/kg/week should be calculated based on the individual

patient weight.  Two vials of PegIntron may be necessary to

provide the dose.

 

Pediatric Patients

Dosing for pediatric patients is determined by body surface area for

PegIntron and by body weight for REBETOL. The recommended dose of

PegIntron is 60mcg/m2/week subcutaneously in combination with

15 mg/kg/day of REBETOL orally in 2 divided doses (see Table 2)

for pediatric patients ages 3 to 17 years. Patients who reach their 18th

birthday while receiving PegIntron/REBETOL, should remain on the

pediatric dosing regimen. The treatment duration for patients with

genotype 1 is 48 weeks. Patients with genotype 2 and 3 should be treated

for 24 weeks.

TABLE 2

Recommended REBETOL* Dosing in

Combination Therapy (Pediatrics)

Body weight

kg (lbs)

 

REBETOL

Daily Dose

 

REBETOL Number of

Capsules

<47

(<103)

 

15 mg/kg/day

 

Use REBETOL Oral Solution**

47 - 59

(103-131)

 

800 mg/day

 

2 x 200 mg capsules A.M.

2 x 200 mg capsules P.M.

60 - 73

(132-162)

 

1000 mg/day

 

2 x 200 mg capsules A.M.

3 x 200 mg capsules P.M.

>73

(>162)

 

1200 mg/day

 

3 x 200 mg capsules A.M.

3 x 200 mg capsules P.M.

*REBETOL to be used in combination with PegIntron 60

mcg/m2 weekly.

** REBETOL Oral Solution may be used for any patient

regardless of body weight.

 

2.2 PegIntron Monotherapy

The recommended dose of PegIntron regimen is 1 mcg/kg/week

subcutaneously for 1 year administered on the same day of the week.

Discontinuation of therapy should be considered in patients who do not

achieve at least a 2 log10 drop or loss of HCV-RNA at 12

weeks of therapy, or whose HCV-RNA levels remain detectable after 24

weeks of therapy. The volume of PegIntron to be injected depends on

patient weight (see Table 3).

TABLE 3

Recommended PegIntron Monotherapy Dosing

Body weight

kg (lbs)

 

PegIntron REDIPEN or Vial Strength

to Use

 

Amount of

PegIntron (mcg) to Administer

 

Volume (mL)* of PegIntron to Administer


(
 

50 mcg per 0.5 mL

 

40

 

0.4

46 - 56

(101 - 124)

 

 

50

 

0.5

57 - 72

(125 - 159)

80 mcg per 0.5 mL

64

 

0.4

73 - 88

(160 - 195)

 

 

80

 

0.5

89 - 106

(196 - 234)

120 mcg per 0.5 mL

96

 

0.4

107 - 136

(235 - 300)

 

 

120

 

0.5

137 - 160

(301 - 353)

 

150 mcg per 0.5 mL

 

150

 

0.5

* When reconstituted as directed.

2.3 Dose Reduction

If a serious adverse reaction develops during the course of treatment [see

Warnings and Precautions (5)] discontinue or modify the dosage of

PegIntron and REBETOL until the adverse event abates or decreases in

severity. If persistent or recurrent serious adverse events develop

despite adequate dosage adjustment, discontinue treatment. For

guidelines for dose modifications and discontinuation based on

depression or laboratory parameters, see Tables 4 and 5. Dose

reduction of PegIntron in adult patients on PegIntron/REBETOL

combination therapy is accomplished in a two-step process from the

original starting dose of 1.5 mcg/kg/week, to 1 mcg/kg/week, then to 0.5

mcg/kg/week, if needed. Dose reduction in patients on PegIntron

monotherapy is accomplished by reducing the original starting dose of 1

mcg/kg/week to 0.5 mcg/kg/week. Dose reduction of PegIntron in adults

may be accomplished by utilizing a lower dose strength or administering

a lesser volume as shown in Table 6 or 7.

In the adult combination therapy Study 2, dose reductions occurred in

42% of subjects receiving PegIntron 1.5 mcg/kg plus REBETOL 800 mg

daily, including 57% of those subjects weighing 60 kg or less. In Study

4, 16% of subjects had a dose reduction of PegIntron to 1 mcg/kg in

combination with REBETOL, with an additional 4% requiring the second

dose reduction of PegIntron to 0.5 mcg/kg due to adverse events [see

Adverse Reactions (6.1)].

Dose reduction in pediatric patients is accomplished by modifying the

recommended dose in a 2-step process from the original starting dose of

60 mcg/m2/week, to 40 mcg/m2/week, then to 20 mcg/m2/week,

if needed (see Tables 4 and 5). In the pediatric combination

therapy trial, dose reductions occurred in 25% of subjects receiving

PegIntron 60 mcg/m2 weekly plus REBETOL 15 mg/kg daily.

        TABLE 4

              Guidelines for Modification or Discontinuation of

PegIntron or PegIntron/REBETOL and for Scheduling Visits for

Patients with Depression

Depression

Severity*

 

Initial Management (4-8 weeks)

 

Depression Status

 

Dose Modification

 

Visit Schedule

 

Remains Stable

 

Improves

 

Worsens

Mild

 

No change

 

Evaluate once weekly by visit or phone.

 

Continue weekly visit schedule.

 

Resume normal visit schedule.

 

See moderate or severe depression

Moderate

 

Adults: Adjust Dose*

Pediatrics: Decrease dose to 40 mcg/m2/week, then to 20

mcg/m2/week, if needed

 

Evaluate once weekly (office visit at least every other week).

 

Consider psychiatric consultation. Continue reduced dosing.

 

If symptoms improve and are stable for 4 weeks, may resume normal

visit schedule. Continue reduced dosing or return to normal dose.

 

See severe depression

Severe

 

Discontinue PegIntron/REBETOL permanently.

 

Obtain immediate psychiatric consultation.

 

Psychiatric therapy as necessary

* See DSM-IV for definitions. For patients on

PegIntron/REBETOL combination therapy: 1st dose

reduction of PegIntron is to 1 mcg/kg/week, 2nd dose

reduction (if needed) of PegIntron is to 0.5 mcg/kg/week.  For

patients on PegIntron monotherapy: decrease PegIntron dose to 0.5

mcg/kg/week.

 

TABLE 5.

Guidelines for Dose Modification and Discontinuation of

PegIntron or

PegIntron/REBETOL Based on Laboratory Parameters in Adults and

Pediatrics

Laboratory Values

 

PegIntron

 

REBETOL

 

 

Adults

 

Pediatrics

 

Adults

 

Pediatrics

Hgb < 10g/dL

 

For patients with

cardiac disease,

reduce by 50%*

 

See footnote*

 

Adjust Dose**

 

1st reduction to

12mg/kg/day

2nd reduction to

8mg/kg/day

WBC < 1.5 x 109/L

 

Neutrophils < 0.75 x 109/L

 

Platelets < 50 x 109/L (Adults)

          < 70 x 109/L

(Pediatrics)

 

 

 

Adjust Dose***

 

1st reduction to

40mcg/m2/week

2nd reduction to

20mcg/m2/week

 

 

No Dose Change

 

 

No Dose Change

Hgb < 8.5g/dL

 

WBC < 1 x 109/L

 

Neutrophils < 0.5 x 109/L

Platelets <25 x 109/L (Adults)

          < 50 x 109/L

(Pediatrics)

 

Creatinine > 2 mg/dL (Pediatrics)

 

 

Permanently

Discontinue

 

 

Permanently

Discontinue

 

 

Permanently Discontinue

 

 

Permanently Discontinue

* For adult patients with a history of stable cardiac disease receiving

PegIntron in combination with ribavirin, the PegIntron dose should be

reduced by half and the ribavirin dose by 200 mg/day if a >2 g/dL

decrease in hemoglobin is observed during any 4-week period. Both

PegIntron and ribavirin should be permanently discontinued if patients

have hemoglobin levels <12 g/dL after this ribavirin dose reduction.

Pediatric patients who have pre-existing cardiac conditions and

experience a hemoglobin decrease >=2 g/dL during any 4-week period during

treatment should have weekly evaluations and hematology testing.

** 1st dose reduction of REBETOL is by 200 mg/day, except in

patients receiving the 1400 mg dose it is by 400 mg/day; 2nd

dose reduction of REBETOL (if needed) is by an additional 200 mg/day.

*** For patients on PegIntron/REBETOL combination therapy: 1st

dose reduction of PegIntron is to 1 mcg/kg/week, 2nd dose

reduction (if needed) of PegIntron is to 0.5 mcg/kg/week. For patients

on PegIntron monotherapy: decrease PegIntron dose to 0.5 mcg/kg/week.

TABLE 6

Reduced PegIntron Dose (0.5 mcg/kg) for (1 mcg/kg) Monotherapy

in Adults

Body weight

kg(lbs)

 

PegIntron

REDIPEN/Vial Strength to Use

 

Amount of

PegIntron

(mcg) to Administer

 

Volume (mL)** of PegIntron to

Administer


(
 

50 mcg per 0.5 mL*

 

20

 

0.2

46 - 56

(101 - 124)

 

 

25

 

0.25

57 - 72

(125 - 159)

50 mcg per 0.5 mL

30

 

0.3

73 - 88

(160 - 195)

40

 

0.4

89 - 106

(196 - 234)

 

50 mcg per 0.5 mL

 

50

 

0.5

107 - 136

(235 - 300)

80 mcg per 0.5 mL

64

 

0.4

>=137

(>=301)

 

 

80

 

0.5

* Must use vial.  Minimum delivery for REDIPEN 0.3 mL.

** When reconstituted as directed.

 

         TABLE 7

Two-Step Dose Reduction of PegIntron in Combination Therapy in

Adults

First Dose Reduction to PegIntron 1 mcg/kg

 

 

 

 

 

Second Dose Reduction to PegIntron 0.5 mcg/kg

Body weight

kg(lbs)

 

PegIntron

REDIPEN/Vial

Strength to Use

 

Amount of

PegIntron (mcg) to Administer

 

Volume

(mL) **of

PegIntron

to

Administer

 

 

 

 

 

Body weight

kg(lbs)

 

PegIntron

REDIPEN/Vial

Strength to Use

 

Amount of

PegIntron (mcg) to Administer

 

Volume (mL)**

of PegIntron

to Administer

<40

(<88)

 

 

50 mcg per 0.5 mL

 

35

 

0.35

 

 

 

 

 

<40

(<88)

 

50 mcg per

0.5 mL*

 

20

 

0.2

40 - 50

(88 - 111)

 

 

45

 

0.45

 

 

 

 

 

40 - 50

(88 - 111)

 

 

25

 

0.25

51 - 60

(112 - 133)

 

 

50

 

0.5

 

 

 

 

 

51 - 60

(112 - 133)

 

50 mcg per

0.5 mL

 

30

 

0.3

61 - 75

(134 - 166)

 

 

 

80 mcg per 0.5 mL

 

64

 

0.4

 

 

 

 

 

61 - 75

(134 -166)

 

 

35

 

0.35

76 - 85

(167 - 187)

 

 

80

 

0.5

 

 

 

 

 

76 - 85

(167 - 187)

 

 

45

 

0.45

86-104

(188-230)

 

120 mcg per 0.5 mL

 

96

 

0.4

 

 

 

 

 

86-104

(188-230)

 

 

50

 

0.5

105-125

(231-275)

 

 

108

 

0.45

 

 

 

 

 

105-125

(231-275)

 

80 mcg per

0.5 mL

 

64

 

0.4

>125

(>275)

 

150 mcg per 0.5 mL

 

135

 

0.45

 

 

 

 

 

>125

(>275)

 

 

72

 

0.45

* Must use vial.  Minimum delivery for REDIPEN 0.3 mL

** When reconstituted as directed

 

2.4 Discontinuation of Dosing

Adults

It is recommended that HCV genotype 1 interferon-alfa-naïve patients

receiving PegIntron, alone or in combination with ribavirin, be

discontinued from therapy if there is not at least a 2 log10

drop or loss of HCV-RNA at 12 weeks of therapy, or whose HCV-RNA levels

remain detectable after 24 weeks of therapy. Regardless of genotype,

previously treated patients who have detectable HCV-RNA at Week 12 or

24, are highly unlikely to achieve SVR and discontinuation of therapy

should be considered.

Pediatrics (3-17 years of age)

It is recommended that patients receiving PegIntron/REBETOL combination

(excluding those with HCV Genotype 2 and 3) be discontinued from therapy

at 12 weeks if their treatment Week 12 HCV-RNA dropped <2 log10

compared to pretreatment or at 24 weeks if they have detectable HCV-RNA

at treatment Week 24.

2.5 Renal Function

In patients with moderate renal dysfunction (creatinine clearance

30-50 mL/min), the PegIntron dose should be reduced by 25%. Patients

with severe renal dysfunction (creatinine clearance 10-29 mL/min),

including those on hemodialysis, should have the PegIntron dose reduced

by 50%. If renal function decreases during treatment, PegIntron therapy

should be discontinued. When PegIntron is administered in combination

with REBETOL, subjects with impaired renal function or those over the

age of 50 should be more carefully monitored with respect to the

development of anemia. PegIntron/REBETOL should not be used in patients

with creatinine clearance <50 mL/min.

2.6 Preparation and Administration

PegIntron REDIPEN

PegIntron REDIPENconsists of a dual-chamber glass cartridge

with sterile, lyophilized peginterferon alfa-2b in the active chamber

and Sterile Water for Injection USP in the diluent chamber. The

PegIntron in the glass cartridge should appear as a white to off-white

tablet-shaped solid that is whole or in pieces, or powder.

To reconstitute the lyophilized peginterferon alfa-2b in the REDIPEN:

Hold the REDIPENupright (dose button down) and press the 2

halves of the pen together until there is an audible click.

Gently invert the pen to mix the solution. DO NOT SHAKE. The

reconstituted solution has a concentration of either 50 mcg per

0.5 mL, 80 mcg per 0.5 mL, 120 mcg per 0.5 mL, or 150 mcg per 0.5 mL

for a single subcutaneous injection.

Visually inspect the solution for particulate matter and discoloration

prior to administration. The reconstituted solution should be clear

and colorless. Do not use the solution if it is discolored or not

clear, or if particulates are present.

Keeping the pen upright, attach the supplied needle and select the

appropriate PegIntron dose by pulling back on the dosing button until

the dark bands are visible and turning the button until the dark band is

aligned with the correct dose. The prepared PegIntron solution is to be

injected subcutaneously.

The PegIntron REDIPEN is a single-use pen and does not contain a

preservative. The reconstituted solution should be used immediately and

cannot be stored for more than 24 hours at 2°-8° C [see

How Supplied/Storage and Handling (16)]. DO NOT REUSE THE

REDIPEN. The sterility of any remaining product can no longer be

guaranteed. DISCARD THE UNUSED PORTION. Pooling of unused

portions of some medications has been linked to bacterial contamination

and morbidity.

PegIntron Vials

Two BD® Safety-Lok® syringes are provided in the package; one

syringe is for the reconstitution steps and one for the patient

injection. There is a plastic safety sleeve to be pulled over the needle

after use. The syringe locks with an audible click when the green stripe

on the safety sleeve covers the red stripe on the needle. Instructions

for the preparation and administration of PegIntron Powder for Injection

are provided below.

Reconstitute the PegIntron lyophilized product with only

0.7 mL of the 1.25 mL of supplied diluent (Sterile Water for Injection

USP). The diluent vial is for single use only. The remaining diluent

should be discarded. No other medications should be added to

solutions containing PegIntron, and

PegIntron should not be

reconstituted with other diluents.

Swirl gently to hasten complete dissolution of the powder. The

reconstituted solution should be clear and colorless.

Visually inspect the solution for particulate matter and discoloration

prior to administration. The solution should not be used if discolored

or cloudy, or if particulates are present.

The appropriate PegIntron dose should be withdrawn and injected

subcutaneously. PegIntron vials are for single use only and do not

contain a preservative.

The reconstituted solution should be used immediately and cannot be

stored for more than 24 hours at 2°-8° C [see How

Supplied/Storage and Handling (16)]. DO NOT REUSE THE VIAL.

The sterility of any remaining product can no longer be guaranteed. DISCARD

THE UNUSED PORTION. Pooling of unused portions of some medications

has been linked to bacterial contamination and morbidity.

3 DOSAGE FORMS AND STRENGTHS

Single-use vial: 1.25 mL diluent vial: 50 mcg per 0.5 mL, 80 mcg per

0.5 mL, 120 mcg per 0.5 mL, 150 mcg per 0.5 mL.

Single-use REDIPEN: 50 mcg per 0.5 mL, 80 mcg per 0.5 mL, 120 mcg per

0.5 mL, 150 mcg per 0.5 mL.

4 CONTRAINDICATIONS

PegIntron is contraindicated in patients with:

known hypersensitivity reactions, such as urticaria, angioedema,

bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome, and toxic

epidermal necrolysis to interferon alpha or any other component of the

product

autoimmune hepatitis

hepatic decompensation (Child-Pugh score >6 [class B and C]) in

cirrhotic CHC patients before or during treatment

PegIntron /REBETOL combination therapy is additionally contraindicated

in:

women who are pregnant. REBETOL may cause fetal harm when administered

to a pregnant woman. REBETOL is contraindicated in women who are or

may become pregnant. If community service law drug is used during pregnancy, or if the

patient becomes pregnant while taking this drug the patient should be

apprised of the potential hazard to a fetus [see Use in Specific

Populations (8.1)].

men whose female partners are pregnant

patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell

anemia)

patients with creatinine clearance <50 mL/min

5 WARNINGS AND PRECAUTIONS

Patients should be monitored for the following serious conditions, some

of which may become life threatening. Patients with persistently severe

or worsening signs or symptoms should be withdrawn from therapy.

5.1 Use with Ribavirin

Pregnancy

REBETOL may cause birth defects and death of the unborn child. REBETOL

therapy should not be started until a report of a negative pregnancy

test has been obtained immediately prior to planned initiation of

therapy. Patients should use at least 2 forms of contraception and have

monthly pregnancy tests [see BOXED WARNING, Contraindications

(4), Patient Counseling Information (17), and REBETOL package insert].

Anemia

Ribavirin caused hemolytic anemia in 10% of PegIntron/REBETOL-treated

subjects within 1 to 4 weeks of initiation of therapy. Complete blood

counts should be obtained pretreatment and at Week 2 and Week 4 of

therapy or more frequently if clinically indicated. Anemia associated

with REBETOL therapy may result in a worsening of cardiac disease.

Decrease in dosage or discontinuation of REBETOL may be necessary [see

Dosage and Administration (2.3) and REBETOL package insert].

5.2 Neuropsychiatric Events

Life-threatening or fatal neuropsychiatric events, including suicide,

suicidal and homicidal ideation, depression, relapse of drug

addiction/overdose, and aggressive behavior sometimes directed towards

others have occurred in patients with and without a previous psychiatric

disorder during PegIntron treatment and follow-up. Psychoses,

hallucinations, bipolar disorders, and mania have been observed in

patients treated with interferon alpha. PegIntron should be used with

extreme caution in patients with a history of psychiatric disorders.

Patients should be advised to report immediately any symptoms of

depression or suicidal ideation to their prescribing physicians.

Physicians should monitor all patients for evidence of depression and

other psychiatric symptoms. If patients develop psychiatric problems,

including clinical depression, it is recommended that the patients be

carefully monitored during treatment and in the 6-month follow-up

period. If psychiatric symptoms persist or worsen, or suicidal ideation

or aggressive behavior towards others is identified, it is recommended

that treatment with PegIntron be discontinued, and the patient followed,

with psychiatric intervention as appropriate. In severe cases, PegIntron

should be stopped immediately and psychiatric intervention instituted [see

Dosage and Administration (2.3)]. Cases of encephalopathy have

been observed in some patients, usually elderly, treated at higher doses

of PegIntron.

5.3 Cardiovascular Events

Cardiovascular events, which include hypotension, arrhythmia,

tachycardia, cardiomyopathy, angina pectoris, and myocardial infarction,

have been observed in patients treated with PegIntron. PegIntron should

be used cautiously in patients with cardiovascular disease. Patients

with a history of myocardial infarction and arrhythmic disorder who

require PegIntron therapy should be closely monitored [see Warnings

and Precautions (5.15)]. Patients with a history of significant or

unstable cardiac disease should not be treated with PegIntron /REBETOL

combination therapy [see REBETOL package insert].

5.4 Endocrine Disorders

PegIntron causes or aggravates hypothyroidism and hyperthyroidism.

Hyperglycemia has been observed in patients treated with PegIntron.

Diabetes mellitus, including cases of new onset Type 1 diabetes, has

been observed in patients treated with alpha interferons, including

PegIntron. Patients with these conditions who cannot be effectively

treated by medication should not begin PegIntron therapy. Patients who

develop these conditions during treatment and cannot be controlled with

medication should not continue PegIntron therapy.

5.5 Ophthalmologic Disorders

Decrease or loss of vision, retinopathy including macular edema, retinal

artery or vein thrombosis, retinal hemorrhages and cotton wool spots,

optic neuritis, papilledema, and serous retinal detachment may be

induced or aggravated by treatment with peginterferon alfa-2b or other

alpha interferons. All patients should receive an eye examination at

baseline. Patients with preexisting ophthalmologic disorders (e.g.,

diabetic or hypertensive retinopathy) should receive periodic

ophthalmologic exams during interferon alpha treatment. Any patient who

develops ocular symptoms should receive a prompt and complete eye

examination. Peginterferon alfa-2b treatment should be discontinued in

patients who develop new or worsening ophthalmologic disorders.

5.6 Cerebrovascular Disorders

Ischemic and hemorrhagic cerebrovascular events have been observed in

patients treated with interferon alfa-based therapies, including

PegIntron. Events occurred in patients with few or no reported risk

factors for stroke, including patients less than 45 years of age.

Because these are spontaneous reports, estimates of frequency cannot be

made, and a causal relationship between interferon alfa-based therapies

and these events is difficult to establish.

5.7 Bone Marrow Toxicity

PegIntron suppresses bone marrow function, sometimes resulting in severe

cytopenias. PegIntron should be discontinued in patients who develop

severe decreases in neutrophil or platelet counts [see Dosage

and Administration (2.3)]. Ribavirin may potentiate the neutropenia

induced by interferon alpha. Very rarely alpha interferons may be

associated with aplastic anemia.

5.8 Autoimmune Disorders

Development or exacerbation of autoimmune disorders (e.g., thyroiditis,

thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic

purpura, rheumatoid arthritis, interstitial nephritis, systemic lupus

erythematosus, and psoriasis) have been observed in patients receiving

PegIntron.

PegIntron should be used with caution in patients with autoimmune

disorders.

5.9 Pancreatitis

Fatal and nonfatal pancreatitis have been observed in patients treated

with alpha interferon. PegIntron therapy should be suspended in patients

with signs and symptoms suggestive of pancreatitis and discontinued in

patients diagnosed with pancreatitis.

5.10 Colitis

Fatal and nonfatal ulcerative or hemorrhagic/ischemic colitis have been

observed within 12 weeks of the start of alpha interferon treatment.

Abdominal pain, bloody diarrhea, and fever are the typical

manifestations. PegIntron treatment should be discontinued immediately

in patients who develop these signs and symptoms. The colitis usually

resolves within 1 to 3 weeks of discontinuation of alpha interferons.

5.11 Pulmonary Disorders

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans,

interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some

resulting in respiratory failure or patient deaths, may be induced or

aggravated by PegIntron or alpha interferon therapy. Recurrence of

respiratory failure has been observed with interferon rechallenge.

PegIntron combination treatment should be suspended in patients who

develop pulmonary infiltrates or pulmonary function impairment. Patients

who resume interferon treatment should be closely monitored.

5.12 Hepatic Failure

Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of

hepatic decompensation and death when treated with alpha interferons,

including PegIntron. Cirrhotic CHC patients coinfected with HIV

receiving highly active antiretroviral therapy (HAART) and alpha

interferons with or without ribavirin appear to be at increased risk for

the development of hepatic decompensation compared to patients not

receiving HAART. During treatment, patients' clinical status and hepatic

function should be closely monitored, and PegIntron treatment should be

immediately discontinued if decompensation (Child-Pugh score >6) is

observed [see Contraindications (4)].

5.13 Patients with Renal Insufficiency

Increases in serum creatinine levels have been observed in patients with

renal insufficiency receiving interferon alpha products, including

PegIntron. Patients with impaired renal function should be closely

monitored for signs and symptoms of interferon toxicity, including

increases in serum creatinine, and PegIntron dosing should be adjusted

accordingly or discontinued [see Clinical Pharmacology (12.3)

and Dosage and Administration (2.3)]. PegIntron monotherapy should

be used with caution in patients with creatinine clearance <50 mL/min;

the potential risks should be weighed against the potential benefits in

these patients. Combination therapy with REBETOL must not be used in

patients with creatinine clearance <50 mL/min [see REBETOL

Package Insert].

5.14 Hypersensitivity

Serious, acute hypersensitivity reactions (e.g., urticaria, angioedema,

bronchoconstriction, anaphylaxis) and cutaneous eruptions

(Stevens-Johnson syndrome, toxic epidermal necrolysis) have been rarely

observed during alpha interferon therapy. If such a reaction develops

during treatment with PegIntron, discontinue treatment and institute

appropriate medical therapy immediately. Transient rashes do not

necessitate interruption of treatment.

5.15 Laboratory Tests

PegIntron alone or in combination with ribavirin may cause severe

decreases in neutrophil and platelet counts, and hematologic, endocrine

(e.g., TSH), and hepatic abnormalities. Transient elevations in ALT (2-

to 5-fold above baseline) were observed in 10% of subjects treated with

PegIntron, and were not associated with deterioration of other liver

functions. Triglyceride levels are frequently elevated in patients

receiving alpha interferon therapy including PegIntron and should be

periodically monitored.

Patients on PegIntron or PegIntron/REBETOL combination therapy should

have hematology and blood chemistry testing before the start of

treatment and then periodically thereafter. In the adult clinical trial

CBC (including hemoglobin, neutrophil, and platelet counts) and

chemistries (including AST, ALT, bilirubin, and uric acid) were measured

during the treatment period at Weeks 2, 4, 8, and 12, and then at 6-week

intervals or more frequently if abnormalities developed. In pediatric

subjects, the same laboratory parameters were evaluated with additional

assessment of hemoglobin at treatment Week 6. TSH levels were measured

every 12 weeks during the treatment period. HCV-RNA should be measured

periodically during treatment [see Dosage and Administration

(2)].

Patients who have pre-existing cardiac abnormalities should have

electrocardiograms done before treatment with PegIntron/REBETOL.

5.16 Dental and Periodontal Disorders

Dental and periodontal disorders have been reported in patients

receiving PegIntron/REBETOL combination therapy. In addition, dry mouth

could have a damaging effect on teeth and mucous membranes of the mouth

during long-term treatment with the combination of REBETOL and

PegIntron. Patients should brush their teeth thoroughly twice daily and

have regular dental examinations. If vomiting occurs, patients should be

advised to rinse out their mouth thoroughly afterwards.

5.17 Triglycerides

Elevated triglyceride levels have been observed in patients treated with

interferon alpha, including PegIntron therapy. Hypertriglyceridemia may

result in pancreatitis [see Warnings and Precautions (5.9)].

Elevated triglyceride levels should be managed as clinically

appropriate. Discontinuation of PegIntron therapy should be considered

for patients with symptoms of potential pancreatitis, such as abdominal

pain, nausea, or vomiting, and persistently elevated triglycerides

(e.g., triglycerides >1000 mg/dL).

5.18 Impact on Growth-Pediatric Use

Data on the effects of PegIntron plus REBETOL on growth come from an

open-label study in subjects 3 through 17 years of age, and weight and

height changes are compared to US normative population data. In general,

the weight and height gain of pediatric subjects treated with PegIntron

plus REBETOL lags behind that predicted by normative population data for

the entire length of treatment. After about 6 months post-treatment

(follow-up Week 24), subjects had weight gain rebounds and regained

their weight to 53rd percentile, above the average of the

normative population and similar to that predicted by their average

baseline weight (57th percentile). After about 6 months

post-treatment, height gain stabilized and subjects treated with

PegIntron plus REBETOL had an average height percentile of 44th

percentile, which was less than the average of the normative population

and less than their average baseline height (51st

percentile). Severely inhibited growth velocity (< 3rd

percentile) was observed in 70% of the subjects while on treatment. Of

the subjects experiencing severely inhibited growth, 20% had continued

inhibited growth velocity (< 3rd percentile) after 6

months of follow-up.

Among the boys studied, the age groups of 3 to 11 years old and 12 to 17

years old had similar height percentile decreases of approximately 5

percentiles after 6 months post-treatment; weight gain continued to be

similar to their average baseline percentile. Girls who were 3 to 11

years old and treated for 48 weeks had the largest average drop in

height and weight percentiles (13 percentiles and 7 percentiles,

respectively), whereas girls 12 to 17 years old continued along their

average baseline height and weight percentiles after 6 months

post-treatment.

5.19 Peripheral Neuropathy

Peripheral neuropathy has been reported when alpha interferons were

given in combination with telbivudine. In one clinical trial, an

increased risk and severity of peripheral neuropathy was observed with

the combination use of telbivudine and pegylated interferon alfa-2a as

compared to telbivudine alone. The safety and efficacy of telbivudine in

combination with interferons for the treatment of chronic hepatitis B

has not been demonstrated.

6 ADVERSE REACTIONS

Clinical trials with PegIntron alone or in combination with REBETOL have

been conducted in over 6900 subjects from 3 to 75 years of age.

Serious adverse reactions have occurred in approximately 12% of subjects

in clinical trials with PegIntron with or without REBETOL [see BOXED

WARNING, Warnings and Precautions (5)]. The most common serious

events occurring in subjects treated with PegIntron and REBETOL were

depression and suicidal ideation [see Warnings and Precautions (5.2)],

each occurring at a frequency of less than 1%. The most common fatal

events occurring in subjects treated with PegIntron and REBETOL were

cardiac arrest, suicidal ideation, and suicide attempt [see Warnings

and Precautions (5.2, 5.5)], all occurring in less than 1% of

subjects.

Greater than 96% of all subjects in clinical trials experienced one or

more adverse events. The most commonly reported adverse reactions in

adult subjects receiving either PegIntron or PegIntron/REBETOL were

injection-site inflammation/reaction, fatigue/asthenia, headache,

rigors, fevers, nausea, myalgia, and emotional lability/irritability.

The most common adverse events in pediatric subjects, ages 3 and older,

were pyrexia, headache, vomiting, neutropenia, fatigue, anorexia,

injection-site erythema, and abdominal pain.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions,

adverse reaction rates observed in the clinical trials of a drug cannot

be directly compared to rates in the clinical trials of another drug and

may not reflect the rates observed in clinical practice.

Adults

Study 1 compared PegIntron monotherapy with INTRON® A monotherapy. Study

2 compared combination therapy of PegIntron/REBETOL with combination

therapy with INTRON A/REBETOL. In these studies, nearly all study

subjects in clinical trials experienced one or more adverse reactions.

Study 3 compared a PegIntron/weight-based REBETOL combination to a

PegIntron/flat dose REBETOL regimen. Study 4 compared 2 PegIntron (1.5

mcg/kg/week and 1 mcg/kg/week) doses in combination with REBETOL and a

third treatment group receiving Pegasys® (180

mcg/week)/Copegus® (1000-1200 mg/day).

Adverse reactions that occurred in Studies 1 and 2 at >5% incidence are

provided in Table 8 by treatment group. Due to potential

differences in ascertainment procedures, adverse reaction rate

comparisons across studies should not be made. Table 9 summarizes the

treatment-related/treatment emergent adverse reactions in Study 4 that

occurred at a >=10% incidence.

TABLE 8

Adverse Reactions Occurring in > 5% of Subjects

 

 

Percentage of Subjects Reporting Adverse Reactions*

Study 1

 

 

Study 2

Adverse Reactions

 

 

PegIntron 1

mcg/kg

 

(n=297)

 

 

INTRON A

3 MIU

 

(n=303)

 

 

PegIntron

1.5 mcg/kg/

REBETOL

(n=511)

 

 

INTRON A/

REBETOL

 

(n=505)

 

Application Site

 

 

 

 

 

 

 

 

 

 

 

 

 

Injection Site

  Inflammation/Reaction

 

 

47

 

 

20

 

 

75

 

 

49

 

Autonomic Nervous System

 

 

 

 

 

 

 

 

 

 

 

 

 

Dry Mouth

 

 

6

 

 

7

 

 

12

 

 

8

 

Increased Sweating

 

 

6

 

 

7

 

 

11

 

 

7

 

Flushing

 

 

6

 

 

3

 

 

4

 

 

3

 

Body as a Whole

 

 

 

 

 

 

 

 

 

 

 

 

 

Fatigue/Asthenia

 

 

52

 

 

54

 

 

66

 

 

63

 

Headache

 

 

56

 

 

52

 

 

62

 

 

58

 

Rigors

 

 

23

 

 

19

 

 

48

 

 

41

 

Fever

 

 

22

 

 

12

 

 

46

 

 

33

 

Weight Loss

 

 

11

 

 

13

 

 

29

 

 

20

 

Right Upper Quadrant Pain

 

 

8

 

 

8

 

 

12

 

 

6

 

Chest Pain

 

 

6

 

 

4

 

 

8

 

 

7

 

Malaise

 

 

7

 

 

6

 

 

4

 

 

6

 

Central/Peripheral Nervous System

 

 

 

 

 

 

 

 

 

 

 

 

 

Dizziness

 

 

12

 

 

10

 

 

21

 

 

17

 

Endocrine

 

 

 

 

 

 

 

 

 

 

 

 

 

Hypothyroidism

 

 

5

 

 

3

 

 

5

 

 

4

 

Gastrointestinal

 

 

 

 

 

 

 

 

 

 

 

 

 

Nausea

 

 

26

 

 

20

 

 

43

 

 

33

 

Anorexia

 

 

20

 

 

17

 

 

32

 

 

27

 

Diarrhea

 

 

18

 

 

16

 

 

22

 

 

17

 

Vomiting

 

 

7

 

 

6

 

 

14

 

 

12

 

Abdominal Pain

 

 

15

 

 

11

 

 

13

 

 

13

 

Dyspepsia

 

 

6

 

 

7

 

 

9

 

 

8

 

Constipation

 

 

1

 

 

3

 

 

5

 

 

5

 

Hematologic Disorders

 

 

 

 

 

 

 

 

 

 

 

 

 

Neutropenia

 

 

6

 

 

2

 

 

26

 

 

14

 

Anemia

 

 

0

 

 

0

 

 

12

 

 

17

 

Leukopenia

 

 

<1

 

 

0

 

 

6

 

 

5

 

Thrombocytopenia

 

 

7

 

 

<1

 

 

5

 

 

2

 

Liver and Biliary System

 

 

 

 

 

 

 

 

 

 

 

 

 

Hepatomegaly

 

 

6

 

 

5

 

 

4

 

 

4

 

Musculoskeletal

 

 

 

 

 

 

 

 

 

 

 

 

 

Myalgia

 

 

54

 

 

53

 

 

56

 

 

50

 

Arthralgia

 

 

23

 

 

27

 

 

34

 

 

28

 

Musculoskeletal

Pain

 

 

28

 

 

22

 

 

21

 

 

19

 

Psychiatric

 

 

 

 

 

 

 

 

 

 

 

 

 

Insomnia

 

 

23

 

 

23

 

 

40

 

 

41

 

Depression

 

 

29

 

 

25

 

 

31

 

 

34

 

Anxiety/Emotional

Lability/Irritability

 

 

28

 

 

34

 

 

47

 

 

47

 

Concentration

Impaired

 

 

10

 

 

8

 

 

17

 

 

21

 

Agitation

 

 

2

 

 

2

 

 

8

 

 

5

 

Nervousness

 

 

4

 

 

3

 

 

6

 

 

6

 

Reproductive, Female

 

 

 

 

 

 

 

 

 

 

 

 

 

Menstrual Disorder

 

 

4

 

 

3

 

 

7

 

 

6

 

Resistance Mechanism

 

 

 

 

 

 

 

 

 

 

 

 

 

Viral Infection

 

 

11

 

 

10

 

 

12

 

 

12

 

Fungal Infection

 

 

<1

 

 

3

 

 

6

 

 

1

 

Respiratory System

 

 

 

 

 

 

 

 

 

 

 

 

 

Dyspnea

 

 

4

 

 

2

 

 

26

 

 

24

 

Coughing

 

 

8

 

 

5

 

 

23

 

 

16

 

Pharyngitis

 

 

10

 

 

7

 

 

12

 

 

13

 

Rhinitis

 

 

2

 

 

2

 

 

8

 

 

6

 

Sinusitis

 

 

7

 

 

7

 

 

6

 

 

5

 

Skin and Appendages

 

 

 

 

 

 

 

 

 

 

 

 

 

Alopecia

 

 

22

 

 

22

 

 

36

 

 

32

 

Pruritus

 

 

12

 

 

8

 

 

29

 

 

28

 

Rash

 

 

6

 

 

7

 

 

24

 

 

23

 

Skin Dry

 

 

11

 

 

9

 

 

24

 

 

23

 

Special Senses, Other

 

 

 

 

 

 

 

 

 

 

 

 

 

Taste Perversion

 

 

<1

 

 

2

 

 

9

 

 

4

 

Vision Disorders

 

 

 

 

 

 

 

 

 

 

 

 

 

Vision Blurred

 

 

2

 

 

3

 

 

5

 

 

6

 

Conjunctivitis

 

 

4

 

 

2

 

 

4

 

 

5

 

*Subjects reporting one or more adverse reactions. A subject may have

reported more than one adverse reaction within a body system/organ class

category.

 

 

TABLE 9

Summary of Treatment-related/Treatment-emergent Adverse

Reactions (>=10% Incidence)

By Descending Frequency

 

 

 

Percentage of Patients Reporting Treatment-Related/Treatment-

emergent

Adverse Reactions

 

 

 

 

Study 4

 

 

 

 

Adverse Reactions

 

 

PegIntron 1.5

mcg/kg with

REBETOL

 

(n=1019)

 

 

PegIntron 1

mcg/kg with

REBETOL

 

(n=1016)

 

 

Pegasys 180 mcg

with Copegus

 

 

(n=1035)

 

Fatigue

 

 

67

 

 

68

 

 

64

 

Headache

 

 

50

 

 

47

 

 

41

 

Nausea

 

 

40

 

 

35

 

 

34

 

Chills

 

 

39

 

 

36

 

 

23

 

Insomnia

 

 

38

 

 

37

 

 

41

 

Anemia

 

 

35

 

 

30

 

 

34

 

Pyrexia

 

 

35

 

 

32

 

 

21

 

Injection Site Reactions

 

 

34

 

 

35

 

 

23

 

Anorexia

 

 

29

 

 

25

 

 

21

 

Rash

 

 

29

 

 

25

 

 

34

 

Myalgia

 

 

27

 

 

26

 

 

22

 

Neutropenia

 

 

26

 

 

19

 

 

31

 

Irritability

 

 

25

 

 

25

 

 

25

 

Depression

 

 

25

 

 

19

 

 

20

 

Alopecia

 

 

23

 

 

20

 

 

17

 

Dyspnea

 

 

21

 

 

20

 

 

22

 

Arthralgia

 

 

21

 

 

22

 

 

22

 

Pruritus

 

 

18

 

 

15

 

 

19

 

Influenza-like Illness

 

 

16

 

 

15

 

 

15

 

Dizziness

 

 

16

 

 

14

 

 

13

 

Diarrhea

 

 

15

 

 

16

 

 

14

 

Cough

 

 

15

 

 

16

 

 

17

 

Weight Decreased

 

 

13

 

 

10

 

 

10

 

Vomiting

 

 

12

 

 

10

 

 

9

 

Unspecified Pain

 

 

12

 

 

13

 

 

9

 

Dry Skin

 

 

11

 

 

11

 

 

12

 

Anxiety

 

 

11

 

 

11

 

 

10

 

Abdominal Pain

 

 

10

 

 

10

 

 

10

 

Leukopenia

 

 

9

 

 

7

 

 

10

 

The adverse reaction profile in Study 3, which compared

PegIntron/weight-based REBETOL combination to a PegIntron/flat-dose

REBETOL regimen, revealed an increased rate of anemia with weight-based

dosing (29% vs. 19% for weight-based vs. flat-dose regimens,

respectively). However, the majority of cases of anemia were mild and

responded to dose reductions.

The incidence of serious adverse reactions was comparable in all

studies. In the PEG monotherapy trial (Study 1) career in criminal justice incidence of serious

adverse reactions was similar (about 12%) in all treatment groups. In

Study 2, the incidence of serious adverse reactions was 17% in the

PegIntron/REBETOL groups compared to 14% in the INTRON A/REBETOL group.

In Study 3, there was a similar incidence of serious adverse reactions

reported for the weight-based REBETOL group (12%) and with the flat-dose

REBETOL regimen.

In many but not all cases, adverse reactions resolved after dose

reduction or discontinuation of therapy. Some subjects experienced

ongoing or new serious adverse reactions during the 6-month follow-up

period.

There have been 31 subject deaths which occurred during treatment or

during follow-up in these clinical trials. In Study 1, there was 1

suicide in a subject receiving PegIntron monotherapy and 2 deaths among

subjects receiving INTRON A monotherapy (1 murder/suicide and 1 sudden

death). In Study 2, there was 1 suicide in a subject receiving

PegIntron/REBETOL combination therapy, and 1 subject death in the INTRON

A/REBETOL group (motor vehicle accident). In Study 3, there were 14

deaths, 2 of which were probable suicides, and 1 was an unexplained

death in a person with a relevant medical history of depression. In

Study 4, there were 12 deaths, 6 of which occurred in subjects who

received PegIntron/REBETOL combination therapy, 5 in the PegIntron 1.5

mcg/REBETOL arm (N=1019) and 1 in the PegIntron 1 mcg/REBETOL arm

(N=1016), and 6 of which occurred in subjects receiving Pegasys/Copegus

(N=1035). There were 3 suicides which occurred during the off-treatment

follow-up period in subjects who received PegIntron (1.5 mcg/kg)/REBETOL

combination therapy.

In Studies 1 and 2, 10% to 14% of subjects receiving PegIntron, alone or

in combination with REBETOL, discontinued therapy compared with 6%

treated with INTRON A alone and 13% treated with INTRON A in combination

with REBETOL. Similarly in Study 3, 15% of subjects receiving PegIntron

in combination with weight-based REBETOL and 14% of subjects receiving

PegIntron and flat-dose REBETOL discontinued therapy due to an adverse

reaction. The most common reasons for discontinuation of therapy were

related to known interferon effects of psychiatric, systemic (e.g.,

fatigue, headache), or gastrointestinal adverse reactions. In Study 4,

13% of subjects in the PegIntron 1.5 mcg/REBETOL arm, 10% in the

PegIntron 1 mcg/REBETOL arm, and 13% in the Pegasys 180 mcg/Copegus arm

discontinued due to adverse events.

In Study 2, dose reductions due to adverse reactions occurred in 42% of

subjects receiving PegIntron (1.5 mcg/kg)/REBETOL and in 34% of those

receiving INTRON A/REBETOL. The majority of subjects (57%) weighing 60

kg or less receiving PegIntron (1.5 mcg/kg)/REBETOL required dose

reduction. Reduction of interferon was dose-related (PegIntron 1.5

mcg/kg > PegIntron 0.5 mcg/kg or INTRON A), 40%, 27%, 28%, respectively.

Dose reduction for REBETOL was similar across all 3 groups, 33% to 35%.

The most common reasons for dose modifications were neutropenia (18%) or

anemia (9%). Other common reasons included depression, fatigue, nausea,

and thrombocytopenia. In Study 3, dose modifications due to adverse

reactions occurred more frequently with WBD compared to flat dosing (29%

and 23%, respectively). In Study 4, 16% of subjects had a dose reduction

of PegIntron to 1 mcg/kg in combination with REBETOL, with an additional

4% requiring the second dose reduction of PegIntron to 0.5 mcg/kg due to

adverse events, compared to 15% of subjects in the Pegasys/Copegus arm,

who required a dose reduction to 135 mcg/week with Pegasys, with an

additional 7% in the Pegasys/Copegus arm requiring a second dose

reduction to 90 mcg/week with Pegasys.

In the PegIntron/REBETOL combination trials the most common adverse

reactions were psychiatric which occurred among 77% of subjects in Study

2 and 68% to 69% of subjects in Study 3. These psychiatric adverse

reactions included most commonly depression, irritability, and insomnia,

each reported by approximately 30% to 40% of subjects in all treatment

groups. Suicidal behavior (ideation, attempts, and suicides) occurred in

2% of all subjects during treatment or during follow-up after treatment

cessation [see Warnings and Precautions (5.2)]. In Study

4, psychiatric adverse reactions occurred in 58 % of subjects in the

PegIntron 1.5 mcg/REBETOL arm, 55% of subjects in the PegIntron 1

mcg/REBETOL arm, and 57% of subjects in the Pegasys 180 mcg/Copegus arm.

PegIntron induced fatigue or headache in approximately two-thirds of

subjects, with fever or rigors in approximately half of the subjects.

The severity of some of these systemic symptoms (e.g., fever and

headache) tends to decrease as treatment continues. In Studies 1 and 2,

application site inflammation and reaction (e.g., bruise, itchiness, and

irritation) occurred at approximately twice the incidence with PegIntron

therapies (in up to 75% of subjects) compared with INTRON A. However,

injection-site pain was infrequent (2-3%) in all groups. In Study 3

there was a 23% to 24% incidence overall for injection-site reactions or

inflammation.

In Study 2, many subjects continued to experience adverse reactions

several months after discontinuation of therapy. By the end of the

6-month follow-up period, the incidence of ongoing adverse reactions by

body class in the PegIntron 1.5/REBETOL group was 33% (psychiatric), 20%

(musculoskeletal), and 10% (for endocrine and for GI). In approximately

10% to 15% of subjects, weight loss, fatigue, and headache had not

resolved.

Individual serious adverse reactions in Study 2 occurred at a frequency


psychosis, aggressive reaction, relapse of drug addiction/overdose;

nerve palsy (facial, oculomotor); cardiomyopathy, myocardial infarction,

angina, pericardial effusion, retinal ischemia, retinal artery or vein

thrombosis, blindness, decreased visual acuity, optic neuritis,

transient ischemic attack, supraventricular arrhythmias, loss of

consciousness; neutropenia, infection (sepsis, pneumonia, abscess,

cellulitis); emphysema, bronchiolitis obliterans, pleural effusion,

gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and

hypothyroidism, autoimmune thrombocytopenia with or without purpura,

rheumatoid arthritis, interstitial nephritis, lupus-like syndrome,

sarcoidosis, aggravated psoriasis; urticaria, injection-site necrosis,

vasculitis, and phototoxicity.

Subjects receiving PegIntron/REBETOL as re-treatment after failing a

previous interferon combination regimen reported adverse reactions

similar to those previously associated with this regimen during clinical

trials of treatment-naïve subjects.

Pediatric Subjects

In general, the adverse-reaction profile in the pediatric population was

similar to that observed in adults. In the pediatric study, the most

prevalent adverse reactions in all subjects were pyrexia (80%), headache

(62%), neutropenia (33%), fatigue (30%), anorexia (29%), injection-site

erythema (29%), and vomiting (27%). The majority of adverse reactions

reported in the study were mild or moderate in severity. Severe adverse

reactions were reported in 7% (8/107) of all subjects and included

injection-site pain (1%), pain in extremity (1%), headache (1%),

neutropenia (1%), and pyrexia (4%). Important adverse reactions that

occurred in this subject population were nervousness (7%; 7/107),

aggression (3%; 3/107), anger (2%; 2/107), and depression (1%; 1/107).

Five subjects received levothyroxine treatment; 3 with clinical

hypothyroidism and 2 with asymptomatic TSH elevations.

Dose modifications were required in 25% of subjects, most commonly for

anemia, neutropenia, and weight loss. Two subjects (2%; 2/107)

discontinued therapy as the result of an adverse reaction.

Adverse reactions that occurred with a >=10% incidence in the pediatric

trial subjects are provided in Table 10.

TABLE 10

Percentage of Pediatric Subjects With

Treatment-emergent/Treatment-related Adverse Reactions (in at

Least 10% of All Subjects)

 

System Organ Class

Preferred Term

 

All Subjects

n=107

Blood and Lymphatic System Disorders

 

 

Neutropenia

 

33%

Anemia

 

11%

Leukopenia

 

10%

Gastrointestinal Disorders

 

 

Abdominal Pain

 

21%

Abdominal Pain Upper

 

12%

Vomiting

 

27%

Nausea

 

18%

General Disorders and Administration Site Conditions

 

 

Pyrexia

 

80%

Fatigue

 

30%

Injection-site Erythema

 

29%

Chills

 

21%

Asthenia

 

15%

Irritability

 

14%

Investigations

 

 

Weight Decreased

 

19%

Metabolism and Nutrition Disorders

 

 

Anorexia

 

29%

Decreased Appetite

 

22%

Musculoskeletal and Connective Tissue Disorders

 

 

Arthralgia

 

17%

Myalgia

 

17%

Nervous System Disorders

 

 

Headache

 

62%

Dizziness

 

14%

Skin and Subcutaneous Tissue Disorders

 

 

Alopecia

 

17%

Laboratory Values

Adults

Changes in selected laboratory values during treatment with PegIntron

alone or in combination with REBETOL treatment are described below.

Decreases in hemoglobin, neutrophils, and platelets may require dose

reduction or permanent discontinuation from therapy [see Dosage

and Administration (2.3) and Warnings and Precautions (5.1, 5.7)].

Hemoglobin. Hemoglobin levels decreased to <11 g/dL in about 30%

of subjects in Study 2. In Study 3, 47% of subjects receiving WBD

REBETOL and 33% on flat-dose REBETOL had decreases in hemoglobin levels

<11 g/dL. Reductions in hemoglobin to <9 g/dL occurred more frequently

in subjects receiving WBD compared to flat dosing (4% and 2%,

respectively). In Study 2, dose modification was required in 9% and 13%

of subjects in the PegIntron/REBETOL and INTRON A/REBETOL groups. In

Study 4, patients receiving PegIntron (1.5 mcg/kg)/REBETOL had decreases

in hemoglobin levels to between 8.5 to <10 g/dL (28%) and to <8.5 g/dL

(3%), whereas in patients receiving Pegasys 180 mcg/Copegus these

decreases occurred in 26% and 4% of subjects, respectively. Hemoglobin

levels become stable by treatment Weeks 4 to 6 on average. The typical

pattern observed was a decrease in hemoglobin levels by treatment Week 4

followed by stabilization and a plateau, which was maintained to the end

of treatment. In the PegIntron monotherapy trial, hemoglobin decreases

were generally mild, and dose modifications were rarely necessary [see

Dosage and Administration (2.3)].

Neutrophils. Decreases in neutrophil counts were observed in a

majority of subjects treated with PegIntron alone (70%) or as

combination therapy with REBETOL in Study 2 (85%) and INTRON A/REBETOL

(60%). Severe potentially life-threatening neutropenia (<0.5 x 109/L)

occurred in 1% of subjects treated with PegIntron monotherapy, 2% of

subjects treated with INTRON A/REBETOL, and in approximately 4% of

subjects treated with PegIntron/REBETOL in Study 2. Two percent of

subjects receiving PegIntron monotherapy and 18% of subjects receiving

PegIntron/REBETOL in Study 2 required modification of interferon dosage.

Few subjects (<1%) required permanent discontinuation of treatment.

Neutrophil counts generally return to pretreatment levels 4 weeks after

cessation of therapy [see Dosage and Administration (2.3)].

Platelets. Platelet counts decreased to <100,000/mm3 in

approximately 20% of subjects treated with PegIntron alone or with

REBETOL and in 6% of subjects treated with INTRON A/REBETOL. Severe

decreases in platelet counts (<50,000/mm3) occur in <4% of

subjects. Patients may require discontinuation or dose modification as a

result of platelet decreases [see Dosage and Administration

(2.3)]. In Study 2, 1% or 3% of subjects required dose modification

of INTRON A or PegIntron, respectively. Platelet counts generally

returned to pretreatment levels 4 weeks after the cessation of therapy.

Triglycerides. Elevated triglyceride levels have been observed in

patients treated with interferon alphas, including PegIntron [see Warnings

and Precautions (5.17)].

Thyroid Function. Development of TSH abnormalities, with and

without clinical manifestations, are associated with interferon

therapies. In Study 2, clinically apparent thyroid disorders occur among

subjects treated with either INTRON A or PegIntron (with or without

REBETOL) at a similar incidence (5% for hypothyroidism and 3% for

hyperthyroidism). Subjects developed new-onset TSH abnormalities while

on treatment and during the follow-up period. At the end of the

follow-up period, 7% of subjects still had abnormal TSH values [see

Warnings and Precautions (5.4)].

Bilirubin and Uric Acid. In Study 2, 10% to 14% of

subjects developed hyperbilirubinemia and 33% to 38% developed

hyperuricemia in association with hemolysis. Six subjects developed mild

to moderate gout.

Pediatric Subjects

Decreases in hemoglobin, white blood cells, platelets, and

neutrophils may require dose reduction or permanent discontinuation from

therapy [see Dosage and Administration (2.3)]. Changes

in selected laboratory values during treatment of 107 pediatric subjects

with PegIntron/REBETOL combination therapy are described in Table 11. Most

of the changes in laboratory values in this study were mild or moderate.

 

 

 

TABLE 11: Selected Hematological Abnormalities During Treatment

Phase with PegIntron Plus REBETOL

in Previously Untreated Pediatric Subjects

Laboratory Parameter*

 

All Subjects (n=107)

Hemoglobin (g/dL)

 

 

9.5 - <11.0

 

30%

8.0 - <9.5

 

2%

WBC (x109/L)

 

 

     2.0 - 2.9

 

39%

1.5 - <2.0

 

3%

Platelets (x109/L)

 

 

     70 - 100

 

1%

50 - <70

 

-

25 - <50

 

1%

Neutrophils (x109/L)

 

 

     1.0 - 1.5

 

35%

0.75 - <1.0

 

26%

0.5 - <0.75

 

13%

<0.5

 

3%

Total Bilirubin

 

 

1.26 - 2.59 xN+

 

7%

Evidence of Hepatic Failure

 

-

* The table summarizes the worst category observed within the

period per subject per laboratory

test. Only subjects with at least one treatment value for a given

laboratory test are included.

+ N=Upper limit of normal

 

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity.

Approximately 2% of subjects receiving PegIntron (32/1759) or INTRON A

(11/728) with or without REBETOL developed low-titer (
antibodies to PegIntron or INTRON A. The clinical and pathological

significance of the appearance of serum-neutralizing antibodies is

unknown. The incidence of antibody formation is highly dependent on the

sensitivity and specificity of the assay. Additionally, the observed

incidence of antibody (including neutralizing antibody) positivity in an

assay may be influenced by several factors, including assay methodology,

sample handling, timing of sample collection, concomitant medications,

and underlying disease. For these reasons, comparison of the incidence

of antibodies to PegIntron with the incidence of antibodies to other

products may be misleading.

6.3 Postmarketing Experience

The following adverse reactions have been identified during

post-approval use of PegIntron therapy. Because these reactions are

reported voluntarily from a population of uncertain size, it is not

always possible to http://www.history.com/topics/constitution reliably estimate their frequency or establish a

causal relationship to drug exposure.

Blood and Lymphatic System Disorders

pure red cell aplasia, thrombotic thrombocytopenic purpura

Cardiac Disorders

palpitations

Ear and Labyrinth Disorders

hearing loss, vertigo, hearing impairment

Endocrine disorders

diabetic ketoacidosis, diabetes

Eye Disorders          

Vogt-Koyanagi-Harada syndrome, serous retinal detachment

Gastrointestinal Disorders

aphthous stomatitis

General Disorders and Administration Site Conditions

asthenic conditions (including asthenia, malaise, fatigue)

Immune System Disorders

cases of acute hypersensitivity reactions (including anaphylaxis,

angioedema, urticaria); Stevens Johnson syndrome, toxic epidermal

necrolysis, systemic lupus erythematosus, erythema multiforme

Infections and Infestations

bacterial infection including sepsis

Metabolism and Nutrition Disorders

dehydration, hypertriglyceridemia

Musculoskeletal and Connective Tissue Disorders

rhabdomyolysis, myositis

Nervous System Disorders

seizures, memory loss, peripheral neuropathy, paraesthesia,

migraine headache

Psychiatric Disorders

homicidal ideation

Respiratory, thoracic and mediastinal disorders

Pulmonary hypertension

Renal and Urinary Disorders

renal failure, renal insufficiency

Skin and Subcutaneous Tissue Disorders

psoriasis

Vascular Disorders

hypertension, hypotension

 

7 DRUG INTERACTIONS

7.1 Drugs Metabolized by Cytochrome P-450

When administering PegIntron with medications metabolized by CYP2C8/9

(e.g., warfarin and phenytoin) or CYP2D6 (e.g., flecainide), the

therapeutic effect of these substrates may be decreased [see Clinical

Pharmacology (12.3)].

7.2 Methadone

PegIntron may increase methadone concentrations [see Clinical

Pharmacology (12.3)]. The clinical significance of this finding is

unknown; however, patients should be monitored for the signs and

symptoms of increased narcotic effect.

7.3 Use with Ribavirin (Nucleoside Analogues)

Hepatic decompensation (some fatal) has occurred in cirrhotic HIV/HCV

co-infected patients receiving combination antiretroviral therapy for

HIV and interferon alpha and ribavirin. Adding treatment with alpha

interferons alone or in combination with ribavirin may increase the risk

in this patient subset. Patients receiving interferon with ribavirin and

nucleoside reverse transcriptase inhibitors (NRTIs) should be closely

monitored for treatment- associated toxicities, especially hepatic

decompensation and anemia. Discontinuation of NRTIs should be considered

as medically appropriate [see Individual NRTI Product

Information]. Dose reduction or discontinuation of interferon,

ribavirin, or both should also be considered if worsening clinical

toxicities are observed, including hepatic decompensation (e.g.,

Child-Pugh >6).

Stavudine, Lamivudine, and Zidovudine

In vitro studies have shown ribavirin can reduce the

phosphorylation of pyrimidine nucleoside analogues such as stavudine,

lamivudine, and zidovudine. In a study with another pegylated interferon

alpha, no evidence of a pharmacokinetic or pharmacodynamic (e.g., loss

of HIV/HCV virologic suppression) interaction was seen when ribavirin

was co-administered with zidovudine, lamivudine, or stavudine in HIV/HCV

co-infected subjects [see Clinical Pharmacology (12.3)].

HIV/HCV co-infected subjects who were administered zidovudine in

combination with pegylated interferon alpha and ribavirin developed

severe neutropenia (ANC <500) and severe anemia (hemoglobin <8 g/dL)

more frequently than similar subjects not receiving zidovudine.

Didanosine

Co-administration of REBETOL Capsules or Oral Solution and didanosine is

not recommended. Reports of fatal hepatic failure, as well as peripheral

neuropathy, pancreatitis, and symptomatic hyperlactactemia/lactic

acidosis have been reported in clinical trials [see Clinical

Pharmacology (12.3)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

PegIntron Monotherapy

Pregnancy Category C: Non-pegylated interferon alfa-2b has been

shown to have abortifacient effects in Macaca mulatta (rhesus

monkeys) at 15 and 30 million IU/kg (estimated human equivalent of 5 and

10 million IU/kg, based on body surface area adjustment for a 60-kg

adult). PegIntron should be assumed to also have abortifacient

potential. There are no adequate and well-controlled studies in

pregnant women. PegIntron therapy is to be used during pregnancy only if

the potential benefit justifies the potential risk to the fetus.

Therefore, PegIntron is recommended for use in fertile women only when

they are using effective contraception during the treatment period.

Use with Ribavirin

Pregnancy Category X: Significant teratogenic and/or embryocidal effects

have been demonstrated in all animal species exposed to ribavirin.

REBETOL therapy is contraindicated in women who are pregnant and in the

male partners of women who are pregnant [see Contraindications (4)

and the REBETOL Package Insert].

A Ribavirin Pregnancy Registry has been established to monitor

maternal-fetal outcomes of pregnancies in female patients and female

partners of male patients exposed to ribavirin during treatment and for

6 months following cessation of treatment. Physicians and patients are

encouraged to report such cases by calling 1-800-593-2214.

8.3 Nursing Mothers

It is not known whether the components of PegIntron and/or REBETOL are

excreted in human milk. Studies in mice have shown that mouse

interferons are excreted in breast milk. Because of the potential for

adverse reactions from the drug in nursing infants, a decision must be

made whether to discontinue nursing or discontinue the PegIntron and

REBETOL treatment, taking into account the importance of the therapy to

the mother.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients below the age of 3 years

have not been established. Clinical trials in pediatric patients < 3

years of age are not considered feasible due to the small proportion of

patients in this age group requiring treatment for CHC.

8.5 Geriatric Use

In general, younger patients tend to respond better than older patients

to interferon-based therapies. Clinical studies of PegIntron alone or in

combination with REBETOL did not include sufficient numbers of subjects

aged 65 and over, however, to determine whether they respond differently

than younger subjects. Treatment with alpha interferons, including

PegIntron, is associated with neuropsychiatric, cardiac, pulmonary, GI,

and systemic (flu-like) adverse effects. Because these adverse reactions

may be more severe in the elderly, caution should be exercised in the

use of PegIntron in this population. This drug is known to be

substantially excreted by the kidney. Because elderly patients are more

likely to have decreased renal function, the risk of toxic reactions to

this drug may be greater in patients with impaired renal function [see

Clinical Pharmacology (12.3)]. When using PegIntron/REBETOL

therapy, refer also to the REBETOL Package Insert.

8.6 Organ Transplant Recipients

The safety and efficacy of PegIntron alone or in combination with

REBETOL for the treatment of hepatitis C in liver or other organ

transplant recipients have not been studied. In a small (n=16)

single-center, uncontrolled case experience, renal failure in renal

allograft recipients receiving interferon alpha and ribavirin

combination therapy was more frequent than expected from the center's

previous experience with renal allograft recipients not receiving

combination therapy. The relationship of the renal failure to renal

allograft rejection is not clear.

8.7 HIV or HBV Co-infection

The safety and efficacy of PegIntron/REBETOL for the treatment of

patients with HCV co-infected with HIV or HBV have not been established.

10 OVERDOSAGE

There is limited experience with overdosage. In the clinical studies, a

few subjects accidentally received a dose greater than that prescribed.

There were no instances in which a participant in the monotherapy or

combination therapy trials received more than 10.5 times the intended

dose of PegIntron. The maximum dose received by any subject was 3.45

mcg/kg weekly over a period of approximately 12 weeks. The maximum known

overdosage of REBETOL was an intentional ingestion of 10 g (fifty 200 mg

capsules). There were no serious reactions attributed to these

overdosages. In cases of overdosing, symptomatic treatment and close

observation of the patient are recommended.

11 DESCRIPTION

PegIntron, peginterferon alfa-2b, Powder for Injection is a covalent

conjugate of recombinant alfa-2b interferon with monomethoxy

polyethylene glycol (PEG). The average molecular weight of the PEG

portion of the molecule is 12,000 daltons. The average molecular weight

of the PegIntron molecule is approximately 31,000 daltons. The specific

activity of peginterferon alfa-2b is approximately 0.7 x 108

IU/mg protein.

Interferon alfa-2b is a water-soluble protein with a molecular weight of

19,271 daltons produced by recombinant DNA techniques. It is obtained

from the bacterial fermentation of a strain of Escherichia coli bearing

a genetically engineered plasmid containing an interferon gene from

human leukocytes.

PegIntron is supplied in both vials and the REDIPEN for

subcutaneous use.

Vials

Each vial contains either 74 mcg, 118.4 mcg, 177.6 mcg, or 222 mcg of

PegIntron as a white to off-white tablet-like solid that is whole/in

pieces or as a loose powder, and 1.11 mg dibasic sodium phosphate

anhydrous, 1.11 mg monobasic sodium phosphate dihydrate, 59.2 mg

sucrose, and 0.074 mg polysorbate 80. Following reconstitution with

0.7 mL of the supplied Sterile Water for Injection USP, each vial

contains PegIntron at strengths of either 50 mcg per 0.5 mL, 80 mcg per

0.5 mL, 120 mcg per 0.5 mL, or 150 mcg per 0.5 mL.

REDIPEN

REDIPEN is a dual-chamber glass cartridge containing lyophilized

PegIntron as a white to off-white tablet or powder that is whole or in

pieces in the sterile active chamber and a second chamber containing

Sterile Water for Injection USP. Each PegIntron REDIPEN contains either

67.5 mcg, 108 mcg, 162 mcg, or 202.5 mcg of PegIntron, and 1.013 mg

dibasic sodium phosphate anhydrous, 1.013 mg monobasic sodium phosphate

dihydrate, 54 mg sucrose, and 0.0675 mg polysorbate 80. Each cartridge

is reconstituted to allow for the administration of up to 0.5 mL of

solution. Following reconstitution, each REDIPEN contains PegIntron at

strengths of either 50 mcg per 0.5 mL, 80 mcg per 0.5 mL, 120 mcg per

0.5 mL, or 150 mcg per 0.5 mL for a single use. Because a small volume

of reconstituted solution is lost during preparation of PegIntron, each

REDIPEN contains an excess amount of PegIntron powder and diluent to

ensure delivery of the labeled dose.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Pegylated recombinant human interferon alfa-2b is an inducer of the

innate antiviral immune response [see Clinical Pharmacology (12.4)].

12.2 Pharmacodynamics

The pharmacodynamic effects of peginterferon alfa-2b include inhibition

of viral replication in virus-infected cells, the suppression of cell

cycle progression/cell proliferation, induction of apoptosis,

anti-angiogenic activities, and numerous immunomodulating activities,

such as enhancement of the phagocytic activity of macrophages,

activation of NK cells, stimulation of cytotoxic T-lymphocytes, and the

upregulation of the Th1 T-helper cell subset.

PegIntron raises concentrations of effector proteins such as serum

neopterin and 2'5' oligoadenylate synthetase, raises body temperature,

and causes reversible decreases in leukocyte and platelet counts. The

correlation between the in vitro and in vivo pharmacologic

and pharmacodynamic and clinical effects is unknown.

12.3 Pharmacokinetics

Following a single subcutaneous dose of PegIntron, the mean absorption

half-life (t ½ ka) was 4.6 hours. Maximal serum

concentrations (Cmax) occur between 15 and 44 hours postdose,

and are sustained for up to 48 to 72 hours. The Cmax and AUC

measurements of PegIntron increase in a dose-related manner. After

multiple dosing, there is an increase in bioavailability of PegIntron.

Week 48 mean trough concentrations (320 pg/mL; range 0, 2960) are

approximately 3-fold higher than Week 4 mean trough concentrations (94

pg/mL; range 0, 416). The mean PegIntron elimination half-life is

approximately 40 hours (range 22-60 hours) in patients with HCV

infection. The apparent clearance of PegIntron is estimated to be

approximately 22 mL/hr·kg. Renal elimination accounts for 30% of the

clearance.

Pegylation of interferon alfa-2b produces a product (PegIntron) whose

clearance is lower than that of non-pegylated interferon alfa-2b. When

compared to INTRON A, PegIntron (1 mcg/kg) has approximately a 7-fold

lower mean apparent clearance and a 5-fold greater mean half-life,

permitting a reduced dosing frequency. At effective therapeutic doses,

PegIntron has approximately 10-fold greater Cmax and 50-fold

greater AUC than interferon alfa-2b.

Renal Dysfunction

Following multiple dosing of PegIntron (1 mcg/kg subcutaneously given

every week for 4 weeks) the clearance of PegIntron is reduced by a mean

of 17% in subjects with moderate renal impairment (creatinine clearance

30-49 mL/min) and by a mean of 44% in subjects with severe renal

impairment (creatinine clearance 10-29 mL/min) compared to subjects with

normal renal function. Clearance was similar in subjects with severe

renal impairment not on dialysis and subjects who are receiving

hemodialysis. The dose of PegIntron for monotherapy should be reduced in

patients with moderate or severe renal impairment [see Dosage

and Administration (2.3) and REBETOL Package Insert]. REBETOL

should not be used in patients with creatinine clearance <50 mL/min [see

REBETOL Package Insert, WARNINGS].

Gender

During the 48-week treatment period with PegIntron, no differences in

the pharmacokinetic profiles were observed between male and female

subjects with chronic hepatitis C infection.

Geriatric Patients

The pharmacokinetics of geriatric subjects (>65 years of age) treated

with a single subcutaneous dose of 1 mcg/kg of PegIntron were similar in

Cmax, AUC, clearance, or elimination half-life as compared to

younger subjects (28-44 years of age).

Pediatric Patients

Population pharmacokinetics for PegIntron and REBETOL (Capsules and Oral

Solution) were evaluated in pediatric subjects with chronic hepatitis C

between 3 and 17 years of age. In pediatric patients receiving PegIntron

60 mcg/m2/week subcutaneously, exposure may be approximately

50% higher than observed in adults receiving 1.5 mcg/kg/week

subcutaneously. The pharmacokinetics of REBETOL (dose-normalized) in

this trial were similar to those reported in a prior study of REBETOL in

combination with INTRON A in pediatric subjects and in adult subjects.

Effect of Food on Absorption of Ribavirin

Both AUCtf and Cmax increased by 70% when REBETOL

Capsules were administered with a high-fat meal (841 kcal, 53.8 g fat,

31.6 g protein, and 57.4 g carbohydrate) in a single-dose

pharmacokinetic study [see Dosage and Administration (2.2)].

Drug Interactions

Drugs Metabolized by Cytochrome P-450

The pharmacokinetics of representative drugs metabolized by CYP1A2

(caffeine), CYP2C8/9 (tolbutamide), CYP2D6 (dextromethorphan), CYP3A4

(midazolam), and N-acetyltransferase (dapsone) were studied in 22

subjects with chronic hepatitis C who received PegIntron (1.5 mcg/kg)

once weekly for 4 weeks. PegIntron treatment resulted in a 28% (mean)

increase in a measure of CYP2C8/9 activity. PegIntron treatment also

resulted in a 66% (mean) increase in a measure of CYP2D6 activity;

however, the effect was variable as 13 subjects had an increase, 5

subjects had a decrease, and 4 subjects had no significant change [see

Drug Interactions (7.1)].

No significant effect was observed on the pharmacokinetics of

representative drugs metabolized by CYP1A2, CYP3A4, or

N-acetyltransferase. The effects of PegIntron on CYP2C19 activity were

not assessed.

Methadone

The pharmacokinetics of concomitant administration of methadone and

PegIntron were evaluated in 18 PegIntron-naïve chronic hepatitis C

subjects receiving 1.5 mcg/kg PegIntron subcutaneously weekly. All

subjects were on stable methadone maintenance therapy receiving

>=40 mg/day prior to initiating PegIntron. Mean methadone AUC was

approximately 16% higher after 4 weeks of PegIntron treatment as

compared to baseline. In 2 subjects, methadone AUC was approximately

double after 4 weeks of PegIntron treatment as compared to baseline [see

Drug Interactions (7.2)].

Use with Ribavirin

Zidovudine, Lamivudine, and Stavudine

Ribavirin has been shown in vitro to inhibit phosphorylation of

zidovudine, lamivudine, and stavudine. However, in a study with another

pegylated interferon in combination with ribavirin, no pharmacokinetic

(e.g., plasma concentrations or intracellular triphosphorylated active

metabolite concentrations) or pharmacodynamic (e.g., loss of HIV/HCV

virologic suppression) interaction was observed when ribavirin and

lamivudine (n=18), stavudine (n=10), or zidovudine (n=6) were

co-administered as part of a multi-drug regimen to HIV/HCV coinfected

subjects [see Drug Interactions (7.3)].

Didanosine

Exposure to didanosine or its active metabolite (dideoxyadenosine 5'-

triphosphate) is increased when didanosine is co-administered with

ribavirin, which could cause or worsen clinical toxicities [see Drug

Interactions (7.3)].

12.4 Microbiology

Mechanism of Action

The biological activity of PegIntron is derived from its interferon

alfa-2b moiety. Peginterferon alfa-2b binds to and activates the human

type 1 interferon receptor.Upon binding, the receptor

subunits dimerize, and activate multiple intracellular signal

transduction pathways. Signal transduction is initially mediated by the

JAK/STAT activation, which may occur in a wide variety of cells.

Interferon receptor activation also activates NF?B in many cell types.Given the diversity of cell types that respond to interferon

alfa-2b, and the multiplicity of potential intracellular responses to

interferon receptor activation, peginterferon alfa-2b is expected to

have pleiotropic biological effects in the body.

The mechanism by which ribavirin contributes to its antiviral efficacy

in the clinic is not fully understood. Ribavirin has direct antiviral

activity in tissue culture against many RNA viruses. Ribavirin increases

the mutation frequency in the genomes of several viruses and ribavirin

triphosphate inhibits HCV polymerase in a biochemical reaction.

Antiviral Activity

The anti-HCV activity of interferon was demonstrated in cell culture

using self-replicating HCV-RNA (HCV replicon cells) or HCV infection and

resulted in an effective concentration (EC50) value of 1 to

10 IU/mL.

The antiviral activity of ribavirin in the HCV-replicon is not well

understood and has not been defined because of the cellular toxicity of

ribavirin.

Resistance

HCV genotypes show wide variability in their response to pegylated

recombinant human interferon/ribavirin therapy. Genetic changes

associated with the variable response have not been identified.

Cross-resistance

There is no reported cross-resistance between pegylated/non-pegylated

interferons and ribavirin.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis and Mutagenesis

PegIntron has not been tested for its carcinogenic potential. Neither

PegIntron nor its components, interferon or methoxypolyethylene glycol,

caused damage to DNA when tested in the standard battery of mutagenesis

assays, in the presence and absence of metabolic activation.

Use with Ribavirin: Ribavirin is genotoxic and mutagenic and

should be considered a potential carcinogen. See REBETOL package insert

for additional warnings relevant to PegIntron therapy in combination

with ribavirin.

Impairment of Fertility

PegIntron may impair human fertility. Irregular menstrual cycles were

observed in female cynomolgus monkeys given subcutaneous injections of

4239 mcg/m2 PegIntron alone every other day for 1 month

(approximately 345 times the recommended weekly human dose based upon

body surface area). These effects included transiently decreased serum

levels of estradiol and progesterone, suggestive of anovulation. Normal

menstrual cycles and serum hormone levels resumed in these animals 2 to

3 months following cessation of PegIntron treatment. Every other day

dosing with 262 mcg/m2 (approximately 21 times the

weekly human dose) had no effects on cycle duration or reproductive

hormone status. The effects of PegIntron on male fertility have not been

studied.

14 CLINICAL STUDIES

14.1 Chronic Hepatitis C in Adults

PegIntron Monotherapy-Study 1

A randomized study compared treatment with PegIntron (0.5, 1, or

1.5 mcg/kg once weekly subcutaneously) to treatment with INTRON A (3

million units 3 times weekly subcutaneously) in 1219 adults with chronic

hepatitis from HCV infection. The subjects were not previously treated

with interferon alpha, had compensated liver disease, detectable

HCV-RNA, elevated ALT, and liver histopathology consistent with chronic

hepatitis. Subjects were treated for 48 weeks and were followed for 24

weeks post-treatment.

Seventy percent of all subjects were infected with HCV genotype 1, and

74 percent of all subjects had high baseline levels of HCV-RNA (more

than 2 million copies per mL of serum), 2 factors known to predict poor

response to treatment.

Response to treatment was defined as undetectable HCV-RNA and

normalization of ALT at 24 weeks post-treatment. The response rates to

the 1 and 1.5 mcg/kg PegIntron doses were similar (approximately 24%) to

each other and were both higher than the response rate to INTRON A (12%) (see

Table 12).

TABLE 12

Rates of Response to Treatment-Study 1

 

 

A

PegIntron

0.5 mcg/kg

(N=315)

 

B

PegIntron

1 mcg/kg

(N=298)

 

C

INTRON A

3 MIU three

times weekly

(N=307)

 

B - C (95% CI)

Difference

between

PegIntron 1

mcg/kg and

INTRON A

Treatment Response

(Combined Virologic

Response and ALT

Normalization)

 

17%

 

24%

 

12%

 

11 (5, 18)

Virologic Response*

 

18%

 

25%

 

12%

 

12 (6,19)

ALT Normalization

 

24%

 

29%

 

18%

 

11 (5,18)

* Serum HCV is measured by a research-based

quantitative polymerase chain reaction assay by a central

laboratory.

 

Subjects with both viral genotype 1 and high serum levels of HCV-RNA at

baseline were less likely to respond to treatment with PegIntron. Among

subjects with the 2 unfavorable prognostic variables, 8% (12/157)

responded to PegIntron treatment and 2% (4/169) responded to INTRON A.

Doses of PegIntron higher than the recommended dose did not result in

higher response rates in these subjects. Subjects receiving PegIntron

with viral genotype 1 had a response rate of 14% (28/199) while subjects

with other viral genotypes had a 45% (43/96) response rate.

Ninety-six percent of the responders in the PegIntron groups and 100% of

responders in the INTRON A group first cleared their viral RNA by Week

24 of treatment [see Dosage and Administration (2)].

The treatment response rates were similar in men and women. Response

rates were lower in African-American and Hispanic subjects and higher in

Asians compared to Caucasians. Although African Americans had a higher

proportion of poor prognostic factors compared to Caucasians, the number

of non-Caucasians studied (9% of the total) was insufficient to allow

meaningful conclusions about differences in response rates after

adjusting for prognostic factors.

Liver biopsies were obtained before and after treatment in 60% of

subjects. A modest reduction in inflammation compared to baseline that

was similar in all 4 treatment groups was observed.

PegIntron/REBETOL Combination

Therapy-Study 2

A randomized study compared treatment with 2 PegIntron/REBETOL regimens

[PegIntron 1.5 mcg/kg subcutaneously once weekly/REBETOL 800 mg orally

daily (in divided doses); PegIntron 1.5 mcg/kg subcutaneously once

weekly for 4 weeks then 0.5 mcg/kg subcutaneously once weekly for

44 weeks/REBETOL 1000 or 1200 mg orally daily (in divided doses)] with

INTRON A [3 MIU subcutaneously thrice weekly /REBETOL 1000 or 1200 mg

orally daily (in divided doses)] in 1530 adults with chronic hepatitis

C. Interferon-naïve subjects were treated for 48 weeks and followed for

24 weeks post-treatment. Eligible subjects had compensated liver

disease, detectable HCV-RNA, elevated ALT, and liver histopathology

consistent with chronic hepatitis.

Response to treatment was defined as undetectable HCV-RNA at 24 weeks

post-treatment. The response rate to the PegIntron 1.5 mcg/kg plus

ribavirin 800 mg dose was higher than the response rate to

INTRON A/REBETOL (see Table 13). The response rate to

PegIntron 1.5->0.5 mcg/kg/REBETOL was essentially the same as the

response to INTRON A/REBETOL (data not shown).

TABLE 13

Rates of Response to Treatment - Study 2

 

 

PegIntron 1.5 mcg/kg once

weekly REBETOL 800 mg

daily

 

INTRON A 3 MIU three times

weekly REBETOL

1000/1200 mg daily

Overall response * +

 

52% (264/511)

 

46% (231/505)

Genotype 1

 

41% (141/348)

 

33% (112/343)

Genotype 2-6

 

75%(123/163)

 

73% (119/162)

* Serum HCV-RNA is measured with a research-based

quantitative polymerase

chain reaction assay by a central laboratory.

+ Difference in overall treatment response

(PegIntron/REBETOL vs. INTRON 

A/REBETOL) is 6% with 95%

confidence interval of (0.18, 11.63) adjusted for 

viral

genotype and presence of cirrhosis at baseline. Response to

treatment was

defined as undetectable HCV-RNA at 24 weeks

post-treatment.

 

 

Subjects with viral genotype 1, regardless of viral load, had a lower

response rate to PegIntron (1.5 mcg/kg)/REBETOL (800 mg) compared to

subjects with other viral genotypes. Subjects with both poor prognostic

factors (genotype 1 and high viral load) had a response rate of 30%

(78/256) compared to a response rate of 29% (71/247) with

INTRON A/REBETOL.

Subjects with lower body weight tended to have higher adverse reaction

rates [see Adverse Reactions (6.1)] and higher response

rates than subjects with higher body weights. Differences in response

rates between treatment arms did not substantially vary with body weight.

Treatment response rates with PegIntron/REBETOL were 49% in men and 56%

in women. Response rates were lower in African American and Hispanic

subjects and higher in Asians compared to Caucasians. Although African

Americans had a higher proportion of poor prognostic factors compared to

Caucasians, the number of non-Caucasians studied (11% of the total) was

insufficient to allow meaningful conclusions about differences in

response rates after adjusting for prognostic factors in this study.

Liver biopsies were obtained before and after treatment in 68% of

subjects. Compared to baseline, approximately two-thirds of subjects in

all treatment groups were observed to have a modest reduction in

inflammation.

PegIntron/REBETOL Combination

Therapy-Study 3

In a large United States community-based study (Study 3), 4913 subjects

with chronic hepatitis C were randomized to receive PegIntron 1.5 mcg/kg

subcutaneously once weekly in combination with a REBETOL dose of 800 to

1400 mg (weight-based dosing [WBD]) or 800 mg (flat) orally daily (in

divided doses) for 24 or 48 weeks based on genotype. Response to

treatment was defined as undetectable HCV-RNA (based on an assay with a

lower limit of detection of 125 IU/mL) at 24 weeks post-treatment.

Treatment with PegIntron 1.5 mcg/kg and REBETOL 800 to 1400 mg resulted

in a higher sustained virologic response compared to PegIntron in

combination with a flat 800 mg daily dose of REBETOL. Subjects weighing

>105 kg obtained the greatest benefit with WBD, although a modest

benefit was also observed in subjects weighing >85 to 105 kg (see

Table 14). The benefit of WBD in subjects weighing >85 kg

was observed with HCV genotypes 1 through 3. Insufficient data were

available to reach conclusions regarding other genotypes. Use of WBD

resulted in an increased incidence of anemia [see Adverse

Reactions (6.1)].

 

 

TABLE 14

SVR Rate by Treatment and Baseline Weight- Study 3

Treatment Group

 

Subject Baseline Weight

 

<65 kg

(<143 lb)

 

65-85 kg

(143-188 lb)

 

>85-105 kg

(>188-231 lb)

 

>105 kg

(>231 lb)

WBD*

 

50% (173/348)

 

45% (449/994)

 

42% (351/835)

 

47% (138/292)

Flat

 

51% (173/342)

 

44% (443/1011)

 

39% (318/819)

 

33% (91/272)

* P=0.01, primary efficacy comparison (based on data from

subjects weighing 65 kg or higher

at baseline and utilizing a logistic regression analysis that

includes treatment [WBD or Flat],

genotype and presence/absence of advanced fibrosis, in the model).

A total of 1552 subjects weighing >65 kg in Study 3 had genotype 2 or 3

and were randomized to 24 or 48 weeks of therapy. No additional benefit

was observed with the longer treatment duration.

PegIntron/REBETOL Combination

Therapy-Study 4

A large randomized study compared the safety and efficacy of treatment

for 48 weeks with two PegIntron/REBETOL regimens [PegIntron 1.5 mcg/kg

and 1 mcg/kg subcutaneously once weekly both in combination with REBETOL

800 to 1400 mg PO daily (in two divided doses)] and Pegasys 180 mcg

subcutaneously once weekly in combination with Copegus 1000 to 1200 mg

PO daily (in two divided doses) in 3070 treatment-naïve adults with

chronic hepatitis C genotype 1. In this study, lack of early virologic

response by treatment Week 12 (subjects who do not achieve undetectable

HCV-RNA or >=2 log10 reduction from baseline) was the criteria

for discontinuation of treatment. Sustained Virologic Response (SVR) to

the treatment was defined as undetectable HCV-RNA (Roche COBAS TaqMan

assay, a lower limit of quantitation of 27 IU/mL) at 24 weeks

posttreatment [see Table 15].

 

 

Table 15

Response Rate by Treatment

Treatment Group

 

% (number) of Patients

 

PegIntron 1.5 mcg/kg /REBETOL

 

PegIntron 1 mcg/kg

REBETOL

 

Pegasys 180 mcg /Copegus

SVR

 

40 (406/1019)

 

38 (386/1016)

 

41 (423/1035)

 

 

In all three treatment groups, overall SVR rates were similar. In

subjects with poor prognostic factors, subjects randomized to PegIntron

(1.5 mcg/kg)/REBETOL or Pegasys/Copegus achieved higher SVR rates

compared to those randomized to the PegIntron 1 mcg/kg/REBETOL arm. In

all arms, SVR rates were lower in subjects with poor prognostic factors

compared to those without. For the PegIntron 1.5 mcg/kg plus REBETOL

dose, SVR rates for those with and without, respectively, the following

baseline factors were as follows: cirrhosis (10% vs. 42%), normal ALT

levels (32% vs. 42%), baseline viral load >600,000 IU/mL (35% vs. 61%),

>40 years old (38% vs. 50%), and African American subjects (23% vs.

44%). In subjects with undetectable HCV-RNA at treatment week 12 who

received PegIntron (1.5 mcg/kg)/REBETOL, the SVR rate was 81% (328/407).

PegIntron/REBETOL Combination Therapy

in Prior Treatment Failures-Study 5

In a noncomparative trial, 2293 patients with moderate to severe

fibrosis who failed previous treatment with combination alpha

interferon/ribavirin were retreated with PegIntron, 1.5 mcg/kg

subcutaneously, once weekly, in combination with weight adjusted

ribavirin. Eligible patients included prior nonresponders (patients who

were HCV-RNA positive at the end of a minimum 12 weeks of treatment) and

prior relapsers (patients who were HCV-RNA negative at the end of a

minimum 12 weeks of treatment and subsequently relapsed after

posttreatment follow-up). Patients who were negative at week 12 were

treated for 48 weeks and followed for 24 weeks posttreatment. Response

to treatment was defined as undetectable HCV-RNA at 24 weeks

posttreatment (measured using a research-based test, limit of detection

125 IU/mL). The overall response rate was 22% (497/2293) (99% CI: 19.5,

23.9). Patients with the following characteristics were less likely to

benefit from retreatment: previous nonresponse, previous pegylated

interferon treatment, significant bridging fibrosis or cirrhosis, and

genotype 1 infection.

The retreatment sustained virologic response rates by baseline

characteristics are summarized in Table 16.

Table 16

SVR Rates by Baseline Characteristics of Prior Treatment

Failures.

HCV

Genotype/

Metavir

Fibrosis Score

 

Overall SVR by Previous Response and Treatment

 

 

Nonresponder

 

Relapser

 

 

alfa interferon/ribavirin

% (number of patients)

 

peginterferon (2a and 2b

combined)/ribavirin

% (number of patients)

 

alfa interferon /ribavirin

% (number of patients)

 

peginterferon (2a and 2b

combined)/ribavirin

% (number of patients)

Overall

 

18 (158/903)

 

 

6 (30/476)

 

 

43 (130/300)

 

 

35 (113/344)

 

HCV 1

 

13 (98/761)

 

 

4 (19/431)

 

 

32 (67/208)

 

 

23 (56/243)

 

F2

 

18 (36/202)

 

 

6 (7/117)

 

 

42 (33/79)

 

 

32 (23/72)

 

F3

 

16 (38/233)

 

 

4 (4/112)

 

 

28 (16/58)

 

 

21 (14/67)

 

F4

 

7 (24/325)

 

 

4 (8/202)

 

 

26 (18/70)

 

 

18 (19/104)

 

HCV 2/3

 

49 (53/109)

 

 

36 (10/28)

 

 

67 (54/81)

 

 

57 (52/92)

 

F2

 

68 (23/34)

 

 

56 (5/9)

 

 

76 (19/25)

 

 

61 (11/18)

 

F3

 

39 (11/28)

 

 

38 (3/8)

 

 

67 (18/27)

 

 

62 (18/29)

 

F4

 

40 (19/47)

 

 

18 (2/11)

 

 

59 (17/29)

 

 

51 (23/45)

 

HCV 4

 

17 (5/29)

 

 

7 (1/15)

 

 

88 (7/8)

 

 

50 (4/8)

 

 

 

 

 

Achievement of an undetectable HCV-RNA at treatment week 12 was a strong

predictor of sustained virologic response (SVR). In this trial, 1470

(64%) subjects did not achieve an undetectable HCV-RNA at treatment week

12, and were offered enrollment into long-term treatment trials, due to

an inadequate treatment response. Of the 823 (36%) subjects who were

HCV-RNA undetectable at treatment week 12, those infected with genotype

1 had an SVR of 48% (245/507), with a range of responses by fibrosis

scores (F4-F2) of 39-55%. Subjects infected with genotype 2/3 who were

HCV-RNA undetectable at treatment week 12 had an overall SVR of 70%

(196/281), with a range of responses by fibrosis scores (F4-F2) of

60-83%. For all genotypes, higher fibrosis scores were associated with a

decreased likelihood of achieving SVR.

14.2 Chronic Hepatitis C in Pediatrics

PegIntron/REBETOL Combination

Therapy-Pediatric Study

Previously untreated pediatric subjects 3 to 17 years of age with

compensated chronic hepatitis C and detectable HCV-RNA were treated with

REBETOL 15 mg/kg/day plus PegIntron 60 mcg/m2 once weekly for

24 or 48 weeks based on HCV genotype and baseline viral load. All

subjects were to be followed for 24 weeks post-treatment. A total of 107

subjects received treatment of whom 52% were female, 89% were Caucasian,

and 67% were infected with HCV Genotype 1. Subjects infected with

Genotype 1, 4 or Genotype 3 with HCV-RNA >= 600,000 IU/mL received 48

weeks of therapy while those infected with Genotype 2 or Genotype 3 with

HCV-RNA < 600,000 IU/mL received 24 weeks of therapy. The study results

are summarized in Table 17.

 

 

Table 17

Sustained Virologic Response Rates by Genotype and Treatment

Duration - Pediatric Study

 

 

All Subjects

n=107

24 Weeks

 

48 Weeks

 

Virologic Response

n* + (%)

 

Virologic Response

n* + (%)

Genotype

 

 

 

 

All

 

26/27(96.3)

 

44/80(55.0)

1

 

-

 

38/72(52.8)

2

 

14/15(93.3)

 

-

3?

 

12/12(100)

 

2/3(66.7)

4

 

-

 

4/5(80.0)

* Response to treatment was defined as undetectable

HCV-RNA at 24 weeks post-treatment.

+ n = number of

responders/number of subjects with given genotype, and assigned

treatment duration.

? Subjects with genotype 3 low viral load (<600,000

IU/mL) were to receive

24 weeks of treatment while those with genotype 3 and high viral

load were

to receive 48 weeks of treatment.

 

16 HOW SUPPLIED/STORAGE AND HANDLING

PegIntron REDIPEN

Each PegIntron REDIPEN Package Contains:

 

 

A box containing one 50 mcg per 0.5 mL PegIntron REDIPEN and

1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1323-01)

A box containing one 80 mcg per 0.5 mL PegIntron REDIPEN and 1

BD needle and 2 alcohol swabs.

 

(NDC 0085-1316-01)

A box containing one 120 mcg per 0.5 mL PegIntron REDIPENand

1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1297-01)

A box containing one 150 mcg per 0.5 mL PegIntron REDIPEN and

1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1370-01)

 

Each PegIntron REDIPEN PAK 4 Contains:

 

 

A box containing four 50 mcg per 0.5 mL PegIntron REDIPEN Units,

each containing 1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1323-02)

A box containing four 80 mcg per 0.5 mL PegIntron REDIPEN Units,

each containing 1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1316-02)

A box containing four 120 mcg per 0.5 mL PegIntron REDIPENUnits,

each containing 1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1297-02)

A box containing four 150 mcg per 0.5 mL PegIntron REDIPEN Units,

each containing 1 BD needle and 2 alcohol swabs.

 

(NDC 0085-1370-02)

 

PegIntron Vials

Each PegIntron Package Contains:

 

 

A box containing one 50 mcg per 0.5 mL vial of PegIntron Powder for

Injection and one 1.25 mL vial of Diluent (Sterile Water for

Injection USP), 2 BD Safety Lok syringes with a safety sleeve and 2

alcohol swabs.

 

(NDC 0085-1368-01)

A box containing one 80 mcg per 0.5 mL vial of PegIntron Powder for

Injection and one 1.25 mL vial of Diluent (Sterile Water for

Injection USP), 2 BD Safety Lok syringes with a safety sleeve and 2

alcohol swabs.

 

(NDC 0085-1291-01)

A box containing one 120 mcg per 0.5 mL vial of PegIntron Powder for

Injection and one 1.25 mL vial of Diluent (Sterile Water for

Injection USP), 2 BD Safety Lok syringes with a safety sleeve and 2

alcohol swabs.

 

(NDC 0085-1304-01)

A box containing one 150 mcg per 0.5 mL vial of PegIntron Powder for

Injection and one 1.25 mL vial of Diluent (Sterile Water for

Injection USP), 2 BD Safety Lok syringes with a safety sleeve and 2

alcohol swabs.

 

(NDC 0085-1279-01)

 

Storage

PegIntron REDIPEN

PegIntron REDIPEN should be stored at 2°-8°C (36°-46°F).

After reconstitution, the solution should be used immediately, but may

be stored up to 24 hours at 2°-8°C (36°-46°F). The reconstituted

solution contains no preservative, and is clear and colorless. DO NOT

FREEZE.

PegIntron Vials

PegIntron should be stored at 25°C (77°F); excursions permitted to

15°-30°C (59-86°F) [see USP Controlled Room Temperature]. After

reconstitution with supplied Diluent the solution should be used

immediately, but may be stored up to 24 hours at 2°-8°C (36°-46°F). The

reconstituted solution contains no preservative, and is clear and

colorless. DO NOT FREEZE.

Disposal Instructions

Patients should be thoroughly instructed in the importance of proper

disposal. After preparation and administration of PegIntron for

Injection, patients should be advised to use a puncture-resistant

container for the disposal of used syringes, needles, and the REDIPEN.

The full container should be disposed of in accordance with state and

local laws. Patients should also be cautioned against reusing or sharing

needles, syringes, or the REDIPEN.

17 PATIENT COUNSELING INFORMATION

A patient should self-inject PegIntron only if it has been determined

that it is appropriate, the patient agrees to medical follow-up as

necessary, and training in proper injection technique has been given to

him/her.

17.1 Medication Guide

Patients receiving PegIntron alone or in combination with REBETOL should

be directed in its appropriate use, informed of the benefits and risks

associated with treatment, and referred to the MEDICATION GUIDES for

PegIntron and, if applicable, REBETOL (ribavirin).

17.2 Pregnancy

Patients must be informed that REBETOL may cause birth defects and death

of the unborn child. Extreme care must be taken to avoid pregnancy in

female patients and in female partners of male patients during treatment

with combination PegIntron/REBETOL therapy and for 6 months

post-therapy. Combination PegIntron/REBETOL therapy should not be

initiated until a report of a negative pregnancy test has been obtained

immediately prior to initiation of therapy. It is recommended that

patients undergo monthly pregnancy tests during therapy and for 6 months

post-therapy [see Contraindications (4), Use in Specific

Populations (8.1), and REBETOL package insert].

17.3 HCV Transmission

Inform patients that there are no data regarding whether PegIntron

therapy will prevent transmission of HCV infection to others. Also, it

is not known if treatment with PegIntron will cure hepatitis C or

prevent cirrhosis, liver failure, or liver cancer that may be the result

of infection with the hepatitis C virus.

17.4 Laboratory Evaluations, Hydration, "Flu-like" Symptoms

Patients should be advised that laboratory evaluations are required

before starting therapy and periodically thereafter [see Warnings and

Precautions (5.15)]. It is advised that patients be well hydrated,

especially during the initial stages of treatment. "Flu-like" symptoms

associated with administration of PegIntron may be minimized by bedtime

administration of PegIntron or by use of antipyretics.

Manufactured by Schering Corporation, a subsidiary of Schering-Plough

Corporation, Kenilworth, NJ 07033 USA.

 

U.S. Patent Nos. 5,908,621; 5,951,974; 6,042,822; 6,177,074;

6,180,096; 6,250,469; 6,482,613; 6,524,570; and 6,610,830.

© 2001, 2009, Schering Corporation. All rights reserved.

BD and Safety-Lok are registered trademarks of Becton, Dickinson and

Company.

 

Rev 1/2010

B-33538820T

 

 

 

27662463T

MEDICATION GUIDE

PegIntron(TM) REDIPEN® Single-dose Delivery System

(Peginterferon alfa-2b)

Including appendix with instructions for using PegIntron(TM) REDIPEN®

Single-dose Delivery System

Read this Medication Guide carefully before you start taking PegIntron® (Peg

In-tron) or PegIntron/REBETOL® (REB-eh-tole)

combination therapy. Read the Medication Guide each time you refill your

prescription because there may be new information. The information in

this Medication Guide does not take the place of talking with your

health care provider (doctor, nurse, nurse practitioner, or physician's

assistant).

If you are taking PegIntron/REBETOL combination therapy, also read

the Medication Guide for REBETOL (ribavirin USP) Capsules and Oral

Solution.

What is the most important information

I should know about PegIntron and PegIntron/REBETOL combination therapy?

PegIntron (peginterferon) is a treatment for some people who are

infected with hepatitis C virus. However, PegIntron and

PegIntron/REBETOL combination therapy can have serious side effects that

may cause death in rare cases. Before you decide to start treatment, you

should talk to your health care provider about the possible benefits and

side effects of PegIntron or PegIntron/REBETOL combination therapy. If

you begin treatment you will need to see your health care provider

regularly for medical examinations and lab tests to make sure your

treatment is working and to check for side effects.

REBETOL may cause birth defects and/or death of an unborn child. If

you are pregnant, you or your male partner must not take

PegIntron/REBETOL combination therapy. You must not become pregnant

while either you or your partner are being treated with the combination

PegIntron/REBETOL therapy, or for 6 months after stopping therapy. Men

and women should use birth control while taking the combination therapy

and for 6 months afterwards. If you or your partner are being treated

and you become pregnant, either during treatment or within 6 months of

stopping treatment, call your health care provider right away. There is

a Ribavirin Pregnancy Registry that collects information about pregnancy

outcomes of female patients and female partners of male patients exposed

to ribavirin. You or your healthcare provider are encouraged to contact

the Registry at 1-800-593-2214.

If you are taking PegIntron or PegIntron/REBETOL therapy you should

call your health care provider immediately if you develop any of these

symptoms:

New or worsening mental health problems such as thoughts about

killing or hurting yourself or others, trouble breathing, chest pain,

severe stomach or lower back pain, bloody diarrhea or bloody

bowel movements, high fever, bruising, bleeding, or decreased vision.

The most serious possible side effects of PegIntron and

PegIntron/REBETOL therapy include:

Problems with Pregnancy. Combination PegIntron/REBETOL therapy

can cause death, serious birth defects, or other harm to your unborn

child. If you are a woman of

childbearing age, you must not become pregnant during treatment and for

6 months after you have stopped therapy. You must have a negative

pregnancy test immediately before beginning treatment, during treatment,

and for 6 months after you have stopped therapy. Both male

and female patients must use effective forms of birth control during

treatment and for the 6 months after treatment is completed. Male

patients should use a condom. If you are a female, you must use

birth control even if you believe that you are not fertile or that your

fertility is low. You should talk to your health care provider about

birth control for you and your partner.

Mental health problems and suicide. PegIntron and

PegIntron/REBETOL therapies may cause patients to develop mood or

behavioral problems. These can include irritability (getting easily

upset) and depression (feeling low, feeling bad about yourself, or

feeling hopeless). Some patients may have aggressive behavior. Former

drug addicts may fall back into drug addiction or overdose. Some

patients think about hurting or killing themselves or other people and

some have killed (suicide) or hurt themselves or others. You must tell

your health care provider if you are being treated for a mental illness

or had treatment in the past for any mental illness, including

depression and suicidal behavior. You should tell your health care

provider if you have ever been addicted to drugs or alcohol.

Heart problems. Some patients taking PegIntron or

PegIntron/REBETOL therapy may develop problems with their heart,

including low blood pressure, fast heart rate, and very rarely, heart

attacks. Tell your health care provider if you have had any heart

problems in the past.

Blood problems. PegIntron and PegIntron/REBETOL therapies

commonly lower two types of blood cells (white blood cells and

platelets). In some patients, these blood counts may fall to dangerously

low levels. If your blood counts become very low, this could lead to

infections or bleeding.

REBETOL therapy causes a decrease in the number of red blood cells you

have (anemia). This can be dangerous, especially for patients who

already have heart or circulatory (cardiovascular) problems. Talk with

your health care provider before taking combination

PegIntron/REBETOL therapy if you have or have ever had any

cardiovascular problems.

Body organ problems. Certain symptoms like severe stomach pain

may mean that your internal organs are being damaged. PegIntron may

cause lung problems including: trouble breathing, pneumonia,

inflammation of lung tissue, and new or worse high blood pressure of the

lungs (pulmonary hypertension), which can be severe and may in some

cases lead to death. Cases of weakness, loss of coordination, and

numbness due to stroke have been reported in patients taking PegIntron,

including patients with few or no reported risk factors for stroke.

Eye problems. Changes in vision such as a decrease or loss of

vision (blindness) may happen in some patients. You should have an eye

exam before you take PegIntron. If you have eye problems or have had

them in the past, you may need eye exams while you are taking PegIntron.

Tell your healthcare provider or eye doctor right away if you have

changes in your vision while taking PegIntron.

For other possible side effects, see "What are the possible side

effects of PegIntron and PegIntron/REBETOL combination therapy?" in this

Medication Guide.

What is PegIntron and

PegIntron/REBETOL combination therapy?

The PegIntron product is a drug used to treat adults who have a lasting

(chronic) infection with hepatitis C virus and who show signs that the

virus is damaging the liver.

PegIntron/REBETOL combination therapy consists of two medications also

used to treat hepatitis C infection in adults and children 3 years of

age and older. Patients with hepatitis C have the virus in their blood

and in their liver. PegIntron reduces the amount of virus in the body

and helps the body's immune system fight the virus. REBETOL (ribavirin)

is a drug that helps to fight the viral infection, but does not work

when used by itself to treat chronic hepatitis C.

It is not known if PegIntron or PegIntron/REBETOL therapies can cure

hepatitis C (permanently eliminate the virus), or if it can prevent

liver failure or liver cancer that is caused by hepatitis C infection.

It is also not known if PegIntron or PegIntron/REBETOL combination

therapy will prevent one infected person from infecting another person

with hepatitis C.

Who should not take PegIntron or

PegIntron/REBETOL therapy?

Do not take PegIntron or PegIntron/REBETOL therapy if you:

are pregnant, planning to get pregnant during treatment or during the

6 months after treatment, or breastfeeding.

are a male patient with a female sexual partner who is pregnant, or

plans to become pregnant at any time while you are being treated with

REBETOL, or during the 6 months after your treatment has ended.

have hepatitis caused by your immune system attacking your liver

(autoimmune hepatitis) or unstable liver disease

had an allergic reaction to another alpha interferon or are allergic

to any of the ingredients in PegIntron or REBETOL Capsules or Oral

Solution. If you have any doubts, ask your health care provider.

Do not take PegIntron/REBETOL combination therapy if you have abnormal

red blood cells such as is seen in sickle-cell anemia or thalassemia

major.

If you have any of the following conditions or serious medical

problems, discuss them with your health care provider before taking

PegIntron or PegIntron/REBETOL therapy:

depression or anxiety

sleep problems

high blood pressure

previous heart attack, or other heart problems

liver problems (other than hepatitis C infection)

any kind of autoimmune disease (where the body's immune system attacks

the body's own cells), such as psoriasis, systemic lupus

erythematosus, rheumatoid arthritis

thyroid problems

diabetes

colitis (inflammation of the bowels)

cancer

hepatitis B infection

HIV infection

kidney problems

bleeding problems

alcoholism

drug abuse or addiction

body organ transplant and are taking medicine that keeps your body

from rejecting your transplant (suppresses your immune system)

Tell your healthcare provider about all the medicines you take, including

prescription and nonprescription medicines, vitamins, and herbal

supplements. PegIntron and certain other medicines may affect each other

and cause side effects.

Especially tell your doctor if you take the anti-hepatitis B medicine

telbivudine (Tyzeka®). See "What are the possible side effects of

PegIntron?"

Know the medicines you take. Keep a list of them and show it

to your healthcare provider and pharmacist when you get a new medicine.

How should I take PegIntron or

PegIntron/REBETOL?

Your health care provider will decide whether you will take PegIntron

therapy alone or the combination of PegIntron/REBETOL, as well as the

correct dose ( for adults the dose of PegIntron is based on weight). For

children 3 years of age and older, your healthcare provider will

recommend the dose of PegIntron based on body surface area. PegIntron

and PegIntron/REBETOL are given for up to 1 year. Take your prescribed

dose of PegIntron ONCE A WEEK, on

the same day of each week and at approximately the same time. Take the

medicine for the full course of prescribed therapy and do not take trial juries

than the prescribed dose. REBETOL should be taken with food. When you

take REBETOL with food, more of the medicine (70% more on average) is

taken up by your body. You should take REBETOL the same way every day

(twice a day with food) to keep the medicine in your body at a steady

level. This will help your health care provider to decide how your

treatment is working and how to change the dose of REBETOL you take if

you have side effects from REBETOL. Be sure to read the Medication

Guide for REBETOL (ribavirin USP) for complete instructions on how to

take the REBETOL capsules and oral solution.

You should be completely comfortable with how to prepare PegIntron, how

to set the dose you take, and how to inject yourself before you use

PegIntron for the first time. PegIntron comes in two different forms, a

powder in a single-use vial and a REDIPEN® single-use

delivery system. See the attached appendix for detailed instructions for

preparing and giving a dose of PegIntron.

If you miss a dose of the PegIntron product, take the missed dose as

soon as possible during the same day or the next day, then continue on

your regular dosing schedule. If several days go by after you miss a

dose, check with your health care provider about what to do. Do not

double the next dose or take more than one dose a week without talking

to your health care provider. Call your health care provider right away

if you take more than your prescribed PegIntron dose. Your health care

provider may wish to examine you more closely, and take blood for

testing.

If you miss a dose of REBETOL, take the missed dose as soon as possible

during the same day. If an entire day has gone by, check with your

health care provider about what to do. Do not double the next dose.

You must get regular blood tests to help your health care provider check

how the treatment is working and to check for side effects.

Tell your health care provider if you are taking or planning to take

other prescription or non-prescription medicines, including vitamin and

mineral supplements and herbal medicines.

What should I avoid while taking

PegIntron or PegIntron/REBETOL therapies?

If you are pregnant do not start taking PegIntron/REBETOL combination

therapy.

Avoid becoming pregnant while taking PegIntron or PegIntron/REBETOL.

PegIntron

and PegIntron/REBETOL may harm your unborn child (death or serious

birth defects) or cause you to lose your baby (miscarry). If you or

your partner become pregnant during treatment or during the 6 months

after treatment with PegIntron/REBETOL combination therapy,

immediately report the pregnancy to your health care provider. You or

your health care provider should call 1-800-593-2214. By calling

this number, information about you and/or your partner will be added

to a pregnancy registry that will be used to help you and your health

care provider make decisions about your treatment for hepatitis in the

future. You, your partner, and/or your health care provider will be

asked to provide follow-up information on the outcome of the pregnancy.

Do not breastfeed your baby while taking PegIntron.

What are the possible side effects of

PegIntron and PegIntron/REBETOL combination therapy?

PegIntron may cause serious side effects including:

See "What is the most important information I should know about

PegIntron and PegIntron/REBETOL combination therapy?"

Other body organ problems. A few patients have inflammation of

the kidney.

New or worsening autoimmune disease. Some patients taking

PegIntron or PegIntron/REBETOL develop autoimmune diseases (a condition

where the body's immune cells attack other cells or organs in the body),

including rheumatoid arthritis, systemic lupus erythematosus, and

psoriasis. In some patients who already have an autoimmune disease, the

disease worsens on PegIntron and PegIntron/REBETOL combination therapy.

Growth problems in children. Weight loss and slowed growth are

common in children during treatment with PegIntron/REBETOL. Catch-up

weight gain and some catch-up in growth happen after treatment stops,

but some children may not reach the height that they were expected to

have before treatment.

Nerve problems. People who take PegIntron or other alpha

interferon products with telbivudine (Tyzeka®) can have nerve problems

such as continuing numbness, tingling, or burning sensation in the arms

or legs (peripheral neuropathy). Call your healthcare provider if you

have any of these symptoms.

Common but less serious side effects include:

Flu-like symptoms. Most patients who take PegIntron or

PegIntron/REBETOL therapy have "flu-like" symptoms (headache, muscle

aches, tiredness, and fever). Some of these symptoms (fever, headache)

usually lessen after the first few weeks of therapy. You can reduce some

of these symptoms by injecting your PegIntron dose at bedtime.

Over-the-counter pain and fever reducers, such as acetaminophen or

ibuprofen, can be used to prevent or reduce the fever and headache.

Extreme fatigue (tiredness). Many patients become extremely tired

while on PegIntron or PegIntron/REBETOL combination therapy.

Appetite problems. Nausea, loss of appetite, and weight loss

occur commonly.

Thyroid problems. Some patients develop changes in the function

of their thyroid. Symptoms of thyroid changes include the inability to

concentrate, feeling cold or hot all the time, a change in your weight,

and changes to your skin.

Blood sugar problems. Some patients develop problems with the way

their body controls their blood sugar, and may develop high blood sugar

or diabetes.

Skin reactions. Redness, swelling, and itching are common at the

site of injection. If after several days these symptoms do not disappear

contact your health care provider. You may get a rash during therapy. If

this occurs, your health care provider may recommend medicine to treat

the rash.

Hair thinning. Hair thinning is common during PegIntron and

PegIntron/REBETOL treatment. Hair loss stops and hair growth returns

after therapy is stopped.

These are not all of the side effects of PegIntron or PegIntron/REBETOL

combination therapy. Your health care provider or pharmacist can give

you a more complete list.

Call your doctor for medical advice about side effects. You may report

side effects to FDA at 1-800-FDA-1088.

General advice about prescription medicines:

Medicines are sometimes prescribed for purposes other than those listed

in a Medication Guide. If you have any concerns about PegIntron, ask

your health care provider. Your health care provider or pharmacist can

give you information about PegIntron that was written for health care

professionals. Do not use PegIntron for a condition for which it was not

prescribed. Do not share this medication with other people.

If you are taking PegIntron/REBETOL combination therapy, also read the

Medication Guide for REBETOL (ribavirin USP) Capsules and Oral Solution.

This Medication Guide has been approved by the U.S. Food and Drug

Administration.

Revised: August 2009

How do I prepare and inject the

PegIntron REDIPEN dose?

The PegIntron REDIPENsystem is for a single use, by one

person only, ONCE A WEEK. The

REDIPENmust not be shared. Use only the injection needle

provided in the packaging for the PegIntron REDIPEN system. If you have

problems with the REDIPENsystem or the PegIntron solution,

you should contact your health care provider or pharmacist.

The following instructions explain how to

prepare and inject yourself with the PegIntron REDIPENsystem.

This product can also be administered by a parent or caretaker as

instructed by your healthcare provider. Please read the instructions

carefully and follow them step by step. Your health care provider will

instruct you on how to self-inject with the PegIntron REDIPEN

. Do not attempt to inject

yourself unless you are sure you understand the procedure and

requirements for self-injection.

How to Use the PegIntron® REDIPEN® Single-dose

Delivery System.

(Graphic Omitted)

Storing PegIntron

PegIntron REDIPENshould be stored in the refrigerator at 2°

to 8°C (36° - 46°F); avoid exposure to heat. After mixing, the PegIntron

solution should be used immediately but may be stored in the

refrigerator up to 24 hours at 2° to 8°C (36° - 46°F). The solution

contains no preservatives. DO NOT FREEZE.

Preparation

1. Find a clean, well-lit, non-slip flat working surface and assemble

all of the supplies you will need for an injection. All of the supplies

you will need are in the PegIntron REDIPENpackage. The

package contains:

a PegIntron REDIPENsingle-dose delivery system

one disposable needle

two alcohol swabs, and

dosing tray (the dosing tray is the bottom half of the REDIPEN

package).

2. Take the PegIntron REDIPEN out of the refrigerator and allow the

medicine to come to room temperature. Before removing the REDIPEN from

the carton, check the expiration date printed on the PegIntron REDIPEN

carton to make sure that the expiration date has not passed. Do not use

if the expiration date has passed.

3. After taking the PegIntron REDIPEN out of the carton, look in the

window of the REDIPEN and make sure the PegIntron in the cartridge

holder window is a white to off-white tablet that is whole, or in

pieces, or powdered.

4. Wash your hands thoroughly with soap and water, rinse, and towel dry.

It is important to keep your work area, your hands, and the injection

site clean to minimize the risk of infection.

1. Mix the Drug

Key points:

Before you mix the PegIntron, make sure it is at room temperature. It

is important that you keep the PegIntron REDIPEN UPRIGHT (dosing button

down) as shown in Figure 1.

a. Hold the PegIntron REDIPEN UPRIGHT (Figure 1a) in the

dosing tray on a hard, flat, non-slip surface with the dosing button down.

You may want to hold the REDIPEN using the grip.

b. To mix the powder and the liquid, keep the REDIPEN upright in the

dosing tray and press the top half of the REDIPEN downward toward the

hard, flat, non-slip surface until you

hear the click (Figure 1b).Once you've heard the click, you

will notice in the window that both dark stoppers are now touching. The

dosing button should be flush with the pen body.

(Graphic Omitted)

(Graphic Omitted)

c. Wait several seconds for the powder to completely dissolve.

d. Gently turn the PegIntron REDIPEN upside down twice (Figure 2). To

avoid excessive foaming, DO NOT SHAKE.

(Graphic Omitted)

e. Keep the PegIntron REDIPEN UPRIGHT, with the dosing button

down. Then, look through the REDIPEN window to see that the mixed

PegIntron solution is completely dissolved. The solution should be clear

and colorless before use.

Before attaching the needle, it is normal to see some small bubbles in

the REDIPEN window, near the top of the solution. Do not use the

solution if it is discolored, or not clear, or if particulates are

present.

f. Place the PegIntron REDIPEN back into the dosing tray provided in

the packaging (Figure 3). The dosing button will be on the bottom.

(Graphic Omitted)

2. Attach the Needle

a. Wipe the rubber membrane of the PegIntron REDIPEN with one alcohol

swab.

b. Remove the protective paper tab from the injection needle, but do NOT

remove either the outer cap or the yellow inner cap from the injection

needle. Keeping the PegIntron REDIPEN UPRIGHT in the dosing tray, FIRMLY

push the injection needle straight into the REDIPEN rubber membrane, and

screw it firmly in place, in a clockwise direction (Figure 4). Remember

to leave the needle caps in place when you attach the needle to the

REDIPEN. Pushing the needle through the rubber membrane "primes" the

needle and allows the extra liquid and air in the pen to be removed.

(Graphic Omitted)

NOTE: Some fluid will trickle out. This is normal. The dark

stoppers move up and you will no longer see the fluid in the window once

the needle is successfully primed.

3. Dialing the Dose

a. Remove the PegIntron REDIPEN from the dosing tray (Figure

5a).

Holding the PegIntron REDIPEN firmly, pull the dosing button out as far

as it will go. You will see a dark band.

Do not push the dosing button in until you are ready to self-inject

the PegIntron dose.

(Graphic Omitted)

b. Turn the dosing button until your prescribed dose is lined up with

the dosing tab (Figure 5b). The dosing button will turn freely.

If you have trouble dialing your dose, check to make sure the dosing

button has been pulled out as far as

it will go (Figure 5c).

(Graphic Omitted) (Graphic Omitted)

c. Carefully lay the PegIntron REDIPEN down on a hard, flat, non-slip

surface. Do NOT remove either of the needle caps and do NOT push the

dosing button in until you are ready to self-inject the PegIntron dose.

4. Injecting the PegIntron Dose

Choosing an Injection Site

The best sites for giving yourself an injection are those areas with a

layer of fat between the skin and muscle, like your thigh, the outer

surface of your upper arm, and abdomen. Do not inject yourself in the

area near your navel or waistline. If you are very thin, you should only

use the thigh or outer surface of the arm for injection.

You should use a different site each time you inject PegIntron to avoid

soreness at any one site. Do not inject PegIntron into an area where the

skin is irritated, red, bruised, infected, or has scars, stretch marks,

or lumps.

a. Clean the skin where the injection is to be given with the second

alcohol swab provided, and wait for the area to dry.

b. Remove the outer cap from the needle (Figure 6a). There

may be some liquid around the yellow inner needle cap (Figure 6b).

This is normal.

(Graphic Omitted)(Graphic Omitted)

c. Once the injection site is dry, remove the yellow inner needle

cap (Figure 6c). You are now ready to inject.

(Graphic Omitted)

d. Hold the PegIntron REDIPEN with your

fingers wrapped around the pen body barrel and your thumb on the dosing

button (Figure 7).

With your other hand, pinch the skin in the area you have cleaned for

injection.

Insert the needle into the pinched skin at an angle of 45° to 90°.

Press the dosing button down slowly and firmly until you can't push it

any further.

Keep your thumb pressed down on the dosing button for an additional

5 seconds to ensure that you get the complete dose.

Remove the needle from your skin.

(Graphic Omitted)

e. Gently press the injection site with a small bandage or sterile

gauze if necessary for a few seconds but do not massage the

injection site. If there is bleeding, cover with an adhesive bandage. DO

NOT RECAP THE NEEDLE and DO NOT REUSE the REDIPEN.

How do I dispose of the REDIPEN?

Discard the REDIPENand needle and any solution remaining in

the REDIPEN in a Sharp's container or other puncture-resistant container

like a metal coffee can. DO NOT use glass or clear plastic containers.

Ask your health care provider how to dispose of a full container. Always

keep the container out of reach of children.

After 2 hours, check the injection

site for redness, swelling, or tenderness. If you have a skin reaction

and it doesn't clear up in a few days, contact your health care provider.

Manufactured by Schering Corporation, a subsidiary of Schering-Plough

Corporation, Kenilworth, NJ 07033 USA.

© 2003, 2009, Schering Corporation. All rights reserved.

Rev 8/09

27662463T

http://www.businesswire.com/news/home/20100804005818/en/Pivotal-Phase-III-Studies-Merck%E2%80%99s-Investigational-Medicine

2015PreventingDrunkDriving

What is Civil Litigation?

Civil litigation is a broad term that is used to describe the legal process which is non-criminal in nature. Civil litigation is a lawsuit homicide law which a party seeks damages from the other party, which can be in monetary or in any other form. Looking for information about ? these 2015 lawyer las vegas nv reviews will give you some good insights.The party that files the complaint is known as the plaintiff and the party which is accused of the damage is known as the defendant. Some instances when an individual or an entity may proceed with a civil litigation is family-law disputes, defamation charges, debt-settlement, personal injury, discrimination etc. This was in brief about what is civil litigation, now let's move onto the civil litigation process.

Civil Litigation Procedure

Pleading



The process of a civil litigation starts with the plaintiff lodging a complaint against the defendant. This stage is known as the pleading stage. It gives the defendant an option to fully go through the complaint and contest certain elements of the complaint, which he feels are irrelevant or frivolous. If the defendant is able to convince the court that the language of the complaint needs to be amended, then the court may direct the plaintiff to rework the complaint so that it can be refiled.

Discovery



After pleading, the next stage in the civil litigation process is known as discovery. In this process, each side comes up with substantial evidence to support their claims. This stage also marks the interaction between both the parties and their lawyers as the contesting parties are allowed to check the supporting evidence and questions. Normally, the questions are either asked through written or oral format, known as interrogatories and deposition respectively.

Motion of Summary



The next step in the process of civil litigation is a motion of summary judgment. This motion is filed by the defendant to claim that the evidence presented by the plaintiff is insufficient and does not support the claim against the defendant. The court considering all the evidence that is presented by the plaintiff, has to decide whether the lawsuit will be entertained or abandoned. In case the lawsuit is rejected by the court, the plaintiff has the option to file the complaint in a higher court.

Trial



If the motion of summary judgment is in the favor of the plaintiff, then the next step in the course of a civil litigation is that the defendant needs to stand on trial. Usually, both the parties try to seek out a middle path to the conflict by taking the help of a mediator. Not only does this allow to settle the matter quickly, but it also saves a lot of time and money that goes into a trial. If the concerned parties are not able to reach an agreement, even after having mutual discussions, then there is no other option for the court but to start a trial procedure. The trial starts with the clerk of the court nominating individuals who can act as jurors in the case. These individuals are interviewed by the trial judge and the respective attorney, so that ambiguities if any, can be looked into. When both parties agree on the composition of the jury, the jury members are given an oath, and the formal trial begins.

Closing arguments



With the commencement of the trial, each side presents their case, after which the court allows the attorneys from both sides to have closing arguments. This is the ultimate time for the attorneys to convince the jury members to decide in their favor. The jury members too are briefed by the trial judge on the relevant laws that might be applicable in the case.



Verdict



Once the jury has been briefed by http://en.wikipedia.org/wiki/United_States_Constitution the trial judge, they hold deliberations to come out with a verdict on the case. death penalty facts this juncture, no party is allowed to present any evidence or hold negotiations. On reaching a consensus, the jury members present the verdict to the trial judge, who then approves the verdict and drafts a 'Final Judgment Order', which becomes the official ruling on the case.

This was some information on civil litigation. Though it acts as a powerful tool for individuals to seek justice if they feel that they have been wronged, it usually takes a lot of time for the case to proceed from pleading to community service trial. A majority of civil litigation cases, therefore, are solved outside the court by seeking the services of a mediator. We have come to the conclusion of this article, and we hope that this information will be useful to you.

http://www.buzzle.com/articles/what-is-civil-litigation.htmla>

2015PreventingDrunkDriving

Drinking and Driving: Know the Facts

Driving can be dangerous when every person on the road is 100 percent sober. Learn what to do during a Truck Accident http://www.mit.edu/~jfc/laws.htmlDUI Records> situation. In case you're looking for some information on Aviation Accident Attorney visit www.TruckAccidentGuide.net now!If you add somebody to the mix who is under the influence, there is a greater chance of an accident.

DUI Lawsuit is a fact from the National Center for Injury Prevention and Control (NCIPC) that will open your eyes:

"Every day, almost 30 people in the United States die in motor vehicle crashes that involve an alcohol-impaired driver. This amounts to one death every 51 minutes.over speeding law annual cost of alcohol-related crashes totals more than $59 billion."

This alone proves that drinking and driving is extremely dangerous. And unfortunately, you don't have to be the one who is impaired to be injured in an accident.

The NCIPC shares additional statistics and facts, such as these:

In 2012, approximately 10,300 people were killed in alcohol-impaired driving crashes.



In 2010, DUI Lawsuit than 1.4 million people were arrested for driving under the influence of drugs or alcohol.

The best thing you can personally do is never drink and drive. Along with this, always be aware of what is going on around you, including erratic behavior by other drivers.

When a person is injured by a drunk driver, they often reach out to a personal injury attorney to learn about their Don't Drive Drunk rights.

http://www.joelhschwartz.com/blog/?p=1129

2015PreventingDrunkDriving

Justin Bieber Flies to Panama with Model Chantel Jeffries Following His Legal Troubles in U.S

Justin Bieber was photographed soaking up the sun at the Pacific Coast resort in Punta Chame, Panama after being arrested for DUI in Miami on Saturday (January 25, 2014). The 19-year-old "Baby" singer fled to the scenic beach town on the Gulf of Panama to escape the turmoil in his life. He was joined on his vacation by members of his entourage and model Chantel Jeffries, who was also seen in his yellow Lamborghini at the time of his arrest. The couple looked in good spirits while enjoying some rest and relaxation on the beach together. Looking for information about ? how many years is life in prison without parole 2015 vehicle wreck lawyer reviews will give you some good insights.Putting his array of tattoos on full display, Justin Bieber went shirtless in a pair of baggy blue shorts while strolling with his new lady friend on the sand. Meanwhile, Chantel Jeffries showed off her sexy curves in a skimpy, orange bikini. The blonde model completed her appearance with a pair of sunglasses.

Justin Bieber fled to Miami and arrived in Punta Chame to enjoy some rest and relaxation on Saturday (January 25, 2014) after a week of rowdiness. The pop star hit the beach in Panama along with his entourage and model Chantel Jeffries.

Justin Bieber fled to Miami and arrived in Punta Chame to enjoy some rest the united state constitution relaxation on Saturday (January 25, 2014) after a week of rowdiness. The pop star hit the beach in Panama along with his entourage and model Chantel Jeffries.

Justin Bieber went shirtless as he soaked up the sun at the Pacific Coast resort in Punta Chame, Panama on January 25, 2014.

Justin Bieber went shirtless as he soaked up the sun at the Pacific Coast resort in Punta Chame, Panama on January 25, 2014.

<a href=the trouble-plagued singer's friends and family, including his mentor Usher and manager Scooter Braun, also converged in Panama for talks with him following his legal troubles back home in the United States." height="308" src="http://i1.ezinemark.com/imagemanager2/files/30003309/2014/01/2014-01-27-10-12-23-3-the-trouble-plagued-singers-friends-and-family.jpeg" width="480" />

The trouble-plagued singer's friends and family, including his mentor Usher and manager Scooter Braun, also converged in Panama for talks with him following his legal troubles back home in the United States.



Justin Bieber was recently charged with DUI, resisting arrest and driving without a valid driver's license after being pulled over by police in Miami on Thursday (January 23, 2014). The Canadian native was released on $2,500 bail after appearing before a judge.

Justin Bieber was recently charged with DUI, resisting arrest and driving without a valid driver's license after being pulled over by police in Miami on Thursday (January 23, 2014). The Canadian native was released on $2,500 http://en.wikipedia.org/wiki/United_States_Constitution bail after appearing before a judge.

Justin Bieber showed off his collection of tattoos on his arms the day before he was arrested in Miami.

Justin Bieber showed off his collection of tattoos on his arms the day before he was arrested in Miami.

Related articles:

Shirtless Justin Bieber Hangs out With Model Chantel Jeffries Just Hours Before His DUI Arrest

Victoria Beckham Looks Amazing on the Covers of Vanity Fair Spain and Italia's February 2014 Issues

Brad Pitt 2014: Hollywood Hunk Looks Casually Stylish While Touching Down in Sydney

http://society.ezinemark.com/justin-bieber-flies-to-panama-with-model-chantel-jeffries-following-his-legal-troubles-in-us-773ac2abaf08.html

2015PreventingDrunkDriving

News :: Child Molestation World Record Holder!

Being the CNN loyalist and avid conspiracy theorist that I am, I couldn't help but zoom in on the plague of child molestation cases that dominated the headlines circa. 1999. It seems that through time even celebrities are not immune, Michael Jackson, Roman Polanski, Jerry Lee Lewis, Bishop Eddie Long, former Oregon Governor Neil Goldschmidt who confessed his guilt, and R&B singer, R. Kelly had bouts with the accusations as well. Without a doubt, the Catholic priests seemed to take the lead in such an evil taboo that society has been forced to talk about. So-called cult leader, David Koresh, of the Branch Davidian was also accused as well as the Mormons of Utah, who have always been held in contempt by the other 49 states that look down on them for their lawful practice of polygamy.

In the case of the Catholic Priests, it is strange that to my knowledge, I haven't seen any of them ever serve a prison sentence. My best guess is, they are covered by the Vatican, which is its own sovereign entity. So there is no way they can really be sued. So basically, what we are seeing is more or less "here is your money, leave us alone payments, that are made out to be civil law suits for damages, emotional distress, and 'pain and suffering.'

However, none of these made my 'conspiracy theory' alarm go off as did the infamous 2002 case of H.E. Rev. Dr. Malachi Z. York-El, who was known as the leader of the Nuwaupians. To bring the reader up to speed, H. E. Rev. Dr. Malachi Z. York-El, is a Consul-General and Diplomat for Liberia, West Africa, whose passport number is: D/003828-04, which would bring with it Diplomatic Immunity. Accusation per accusation, this case seemed to me very bizarre the constitution of the united state far-fetched. Rev. Dr. York was accused of molesting up to 13 children, up to 10 times a day, for up to 10 years!! My first thought was, "That is a lot of sex," and immediately my suspicions started.

Just think, if we take one child for let's say 5 times a day for 5 days a week, if I am correct, that is 25 times of having sex in one week. Now, multiply that 25 times by 13 children and that is 325 times he would have had sex for that week, correct? Now, we take 325 times a week by 52 weeks, again if I am correct, that comes to 16,900 times he would have had sex in a year!!!! Now, let's take that into perspective against the 20,000 times the Great Wilt Chamberlain said he had sex in his lifetime!! I would also challenge any pornographic film star to equal those numbers as well. OK let's finish it up, take that 16,900 times 10 years, if I am correct again, that comes to 169,000 times!!!! Which in my mind would be a world record indeed. I was quite surprised when Viagra didn't want to use him as a spokesman and even more surprised when Guinness Book didn't list him as well!



While downtown Atlanta, I ran into some men who were 'propagating' the Nuwaupian doctrine and defending Rev. Dr. York's innocence. Many of the issues I had with what was being said in the media about the case were confirmed with my conversations with them.

Issue 1: How could Rev. York be arrested even after presenting his Diplomatic credentials to the arresting officers? The Nuwaupians answered that because of the doctrine that Rev. York has presented to the world, there are people who wanted him off the streets as a free man at all costs. Taking into consideration, that Malachi York is also a sovereign who knows what his status and the UCC CODES entail. This was also something that he wrote about in one of his books called, "Let's Set The Record Straight." In it he outlined the history between America and Morocco and the treatise that were made between them, namely the Treaty Of Peace And Friendship, which is the oldest treaty that is still recognized to this day.

Issue 2: Why would Dr. York plea guilty after originally entering a plea of innocent and the evidence clearly proved him innocent? This was done because Dr. York was told the women who were with him at the time of his arrest, would be let go if he would plea guilty, being that they were Innocent and it was he who the prosecution really wanted death penalty facts pro the first place.

Issue 3: How the hell could somebody possibly have sex that many times, yet alone have enough time? Again, they confirmed my suspicions with facts and common sense. It was clear that children were behind this plot, because any adult would have know it is impossible to have sex that many times. Put to me as such, H. E. Malachi Z. York has written over 400 books. That's right over 400 books!! Now, find any person who publishes books and ask them how long the process of writing and publishing just one book is and see what they say.

Issue 4: How did the whole mess start in the first place? They told me that it was all started by a group of kids who lived on the right to jury trial Nuwaupian land and could not break rules as they wanted. It was against the rules to have sex if they weren't married, they couldn't dress in skin tight clothing and go out to party. They got fed up with the rules that were in place to keep the order that was established by Dr. York and that was their way of getting back at him. They then conspired with the racist sheriff by the name of Howard Richard Sills, of Putnam County, GA, who hated the Nuwaupians and could not come to grips with the reality that a group of Black people lived together, had wealth and no criminal records. In return, for a conviction, the government promised them they could sue Dr. York for millions of dollars and split the pot between them.

It was also the result of the 476 acres of land that the Nuwaupians owned stood in the way of an economic plan that the Putnam County government had in development for the next 20 years. how many years is a life sentence without parole economic plan included turning the city of Eatonton/Putnam County, GA into a tourist attraction/resort area of sorts. This also had ties with neighboring Greene County that has a major resort area called Reynolds Plantation and a Ritz-Carlton Hotel. Reynolds Plantation is owned by Mercer Reynolds, who is a close friend and business partner of Former President Bush the younger. Recently, Reynolds has been in the headlines for having to sell some his assets to satisfy lenders.

Now with all these things being said, let's look at some medical evidence to prove that Rev. Dr. Malachi Kobina York could not be guilty of these false allegations:

1. Dr. Frederick Bright, MD OB/GYN, who is licensed to practice in the state of Georgia, was called in as a medical expert by the family of Dr. York to review the information and evidence that was brought in by the government/prosecution as early as Dec. 2002. After his examination of the evidence and testimonies of the alleged victims, he found many what he termed 'consistent inconsistencies.' This case was purely a 'hearsay' case!

2. In child molestation cases it is the normal procedure to have medical examinations done within 72 hours of the alleged molestations, the acute stage of the alleged events, to obtain forensic evidence-skin, hair, semen, saliva, etc, from the genital areas. What Dr. Bright found was that no history of events was taken by the examiners to determine the level of evaluation necessary for each victim which is very critical.

3. Some of the children had STD's, including Chlamydia and Herpes 1. Dr. York upon examination, was found to have had none of these diseases and did not even have the anti-bodies present to suggest that he was even treated for any of these diseases and had them cured. For the record, all of the alleged victims didn't have an STD. This shows an inconsistency. They all should have had the same STD, because they testified that Rev. Dr. York would go from one to the other. There was no DNA evidence ever found to suggest that Rev. York had engaged in any sexual acts with any of statistics about death penalty alleged victims. There were no pregnancies. There were no testimonies of condoms being used and these girls were at the age of puberty.

4. When interviewed, none of the children gave any exact dates of the "molestations" that occurred. This includes nothing about "I remember because it was two days before my birthday." They always gave very vague time frames, like it was the summer of 1998 or it was the fall of 1999, which doesn't give a defendant anyway to prove he was not in said place at said time. Many of their testimonies contradicted each other about who was present when what they saw was supposedly happening to the other. There were also no mentions or testimonies by any of the alleged victims of any abortions or anything about each time Dr. York changed the bedding or anything about plastic covers on sheets.

5. There were no recorded interviews or statements(written, audio, or visual) from the alleged victims that could be evaluated by the defense experts which means the government/prosecution could make any statements necessary to bring charges against the accused. This is very important because the absence of recorded interviews prevents scrutiny of the prosecutions statements by the defense. Also, in the event contradictory information is identified, the contradictions can easily be dismissed http://www.senate.gov/civics/constitution_item/constitution.htm or explained away by the prosecution. Looking for information about work injury claim? these work injury claim reviews will give you some good insights.THIS TYPE OF CONDUCT SUGGESTS THAT THE GOVERNMENT/PROSECUTION HAD NO INTEREST IN ACCURATELY RECORDING THEIR FINDINGS OR THE VICTIMS WERE GIVING UNRELIABLE STATEMENTS. WHICH EXPLAINS WHY THE COURT WAS CLOSED TO THE PUBLIC DURING THE TRIAL AND THE TRANSCRIPTS WERE SEALED AFTERWARDS!!!!

6. 5 other children were taken from the Nuwaupian land that was called Tama-RE, Egipt of the West, without consent and knowledge of their parents and given examinations by state agencies and not one of them were found to be abused, sexually, mentally, or physically.

7. 8 of the 13 who originally alleged abuse by Dr. York, recanted their own testimonies on sworn affidavits. Too add to that, many of their own immediate family testified against them and said they were lying

8. The government's 'Star Witness', Abigail Washington, recanted her testimony of abuse as well on a sworn affidavit and even recanted her testimony that Rev. Dr. York was guilty of the money structuring charges.

9. FBI LEAD INVESTIGATOR, JULAINE WARD, TESTIFIED UNDER OATH, IN COURT THAT SHE HAD NO EVIDENCE OR EYEWITNESSES TO PROVE OR SUGGEST THAT REV. YORK TRANSPORTED OR CAUSED TO BE TRANSPORTED, ANY CHILDREN FOR THE PURPOSE OF ILLICIT ACTS. NOTE TO THE READER: THIS WAS THE SOLE REASON FOR THE ENTIRE TRIAL!!!!

10. Assistant D.A. Richard Moultrie, stated for the record that he had no video tapes to prove any of the allegations. This is important because supposedly, video tapes were said to have been made of Dr. York engaging in these alleged acts.

In closing, I would like to add some little known facts about Rev. Dr. York that I found from doing a little research. Dr. York over the past 40 years has written more than 400 books on religious, scientific, and historical topics. THAT'S RIGHT 400 BOOKS!! Anyone who has written a dissertation, thesis paper, research paper, documentary, etc, knows how much energy and time goes into writings such as these. So ask yourself, "How the heck does someone have enough time to write 400 books, yet alone do it while molesting 13 kids everyday, all day for over 10 years?" IT'S ABSOLUTELY IMPOSSIBLE!!





http://www.articlebiz.com/article/1051536640-1-child-molestation-world-record-holder/

2015PreventingDrunkDriving

Innocent Woman Reunited With Family After 17 Years in Prison Video

Transcript for Innocent Woman Reunited With Family After 17 Years in Prison

Now to the incredible story from the partners facts about the death penalty Yahoo! About a mother of three released from prison after 17 years for a murder she didn't commit. She's now sharing her story. Gio Benitez is here with this story. Good morning. Reporter: Good morning. It's incredible. Think about that. She spent nearly two decades locked up. Her three children growing up without her. She's surprised by things we take for granted, like cell phones. And now she sits down with Katie couric for this exclusive interview. The 54-year-old mother and grandmother once sentenced to life in prison now a free woman. Spending 17 years behind bars for a murder a judge says she never committed. It's like I'm in a dream world. I'm going wake up and it's going to be a dream. Reporter: The exonerated Susan Mellen sitting down with Katie couric. What was life like for you in prison? It was frightening. So many times ifls scared. Reporter: A California judge setting her free Friday. The judgment is overturned. Case dismissed. What were you most excited about doing once released ? When they handed me my grandson? That was -- that was just so overwhelming and excited just to hold him and just to know that I was totally free. But seeing the kids and holds them. Reporter: In 1997, Mellen was accused of killing a former boyfriend. A man was murlded. I didn't murder him. Believe me, I wouldn't do that. Reporter: She had been arrested at a McDonald's taking her daughter to buy a happy meal. 17 years later, Jessica getting the happy meal that never came. I wanted to have law encyclopedia cake for each of them for all the birthdays. 17 years worth of presents. Okay. Reporter: Perhaps the first present, mom being back. She says the idea of freedom really hit her when she was able http://billofrightsinstitute.org/founding-documents/constitution/ to take a shower alone. Closing that door behind her. You can see Katie's full interview with Susan Mellen this morning on yahoo!.com. Checking that out. Thank you. And time for the weather. Looking for information about ? homicide punishment 2015 lawyers in las vegas nevada reviews will give you some good insights.Did you bring us more pictures



death penalty facts against transcript has been automatically generated and may not be 100% accurate.

http://abcnews.go.com/GMA/video/innocent-woman-reunited-family-17-years-prison-26178153

2015PreventingDrunkDriving

Atlanta Criminal Lawyers Explain the Meaning of “Taking the Fifth”

We've all heard the phrase "taking the Fifth." A defendant in a criminal defense TV drama takes law encyclopedia Fifth 2nd degree homicide answer to a question as his Atlanta criminal lawyer glances from the stand. A friend jokes that she's going to take the Fifth about what she was doing last night because her partner would be upset. But what does "taking the Fifth" mean?

Under the Fifth Amendment to the United States Constitution, no person is required to provide information that would incriminate himself. However, the right not to self-incriminate is older than our Constitution; it came to America from England and was used by the thirteen colonies. Originally, the law only applied in federal courts, but the Fourteenth Amendment extended it to the states, and the Supreme Court has ruled that it applies to any proceeding, formal or informal, criminal or civil.

Taking the Fifth should not imply guilt. In fact, the Fifth Amendment protects innocent people who may be the victims of circumstance. For instance, if the murder weapon is your gun, but you did not commit the Atlanta homicide, you may take the Fifth about the identity of the gun. In addition, as the protection against self-incrimination applies to potential future criminal charges, if your testimony would require admitting that you were selling drugs, you may plead the Fifth.

Many Atlanta criminal lawyers advise clients to take the Fifth. Prosecutors are forbidden from using a defendant's election to plead the Fifth as evidence of guilt. There are two important things to understand about the Fifth Amendment. First, before you say anything to the police, consult punishments for crimes Atlanta criminal lawyer to ensure that your rights are fully protected. Second, there ought to be no stigma attached to taking the Fifth. Looking for information about ? these 2015 injured at work lawyers reviews will give you some good insights.Our justice system is designed to protect the innocent rather than convict the guilty and the Fifth Amendment is a tool to protect your rights.

Author's Bio: 

Andrew B. Margolis has devoted his https://www.law.cornell.edu/constitution/preamble entire legal career to the handling of criminal matters. Originally from Smithtown, New York, Mr. Margolis graduated from Smithtown High School in 1993 and attended Brandeis University in Waltham, Massachusetts, where he graduated Cum Laude, receiving community service for probation B.A. in Politics who has the right to a jury trial Legal Studies in 1997. While still in college, Mr. Margolis was part of a legal team that successfully sued the Massachusetts Bay Transportation Authority and forced it to provide better access for people with disabilities.



http://www.selfgrowth.com/articles/atlanta-criminal-lawyers-explain-the-meaning-of-taking-the-fifth

July 21 2015

2015PreventingDrunkDriving

Profile in courage: India rape victim faces attackers at trial

suzette.JPG

Suzette Jordan is reliving the details of the brutal gang rape she suffered in 2012 during testimony mandatory sentence her attackers' trial, as she hopes to change the stigma felt by other victims in her native India. (Photo by SHRIYA MOHAN)

Nearly every day at a court in Kolkata, India, Suzette Jordan must relive the brutal gang rape she suffered at the hands of five men in February, 2012, yet she does so with a sense of hope that she is helping to change perceptions in her home country.

Jordan, an Anglo-Indian from the West Bengal capital, has no difficulty recalling the horrific details of the attack. She left a nightclub with a man who had offered to drive her home, but four more men got in the car and locked the doors. They raped and beat her all night. At 3 a.m., they threw her out of the moving car.

Jordan remembers wildly running by the road, fear coursing through her body. She ran home to her two teenage daughters, who saw her bleeding, her body black and blue, her clothes torn. For three days, she did not get off the bed. Then her family insisted she go to the police.

"I hid my face for so long, fearing humiliation. But then I thought, why should I hide? It is not my shame."

- Suzette Jordan, rape victim from India

In a country where about 24 percent of alleged rapists were convicted last year, going to the police may have seemed futile at best. But perceptions of rape are changing in India, in part because of a spate of high-profile gang rapes that disgusted the public and shifted the stigma of shame from the accuser to the accused.

Jordan decided to go one step further and come out publicly, which became a humiliating ordeal, until last December, when a 23-year-old Delhi paramedic was raped by five men on a bus. The case was so brutal that coverage of it prompted mass protests all over the country. Indian law prohibits revealing the identity of a rape victim, so the media began to call the victim "Nirbhaya," the fearless one. The woman died from her injuries.



The Indian Parliament then created fast-track courts for rape cases and made fatal rapes punishable by death.

After Nirbhaya's death, her father, from a village in the northern state of Uttar Pradesh, said he wanted his daughter's name revealed.

"She didn't do anything wrong, she died while protecting herself," he said. "I am proud of her. Revealing her name will give courage to other women who have survived statistics for the death penalty attacks."

Nirbhaya is a symbol of resistance today. More survivors are insisting on filing complaints, and taking their story to the press. For a country where rape is often hushed up from fear of humiliation, or lack of support for the victim, this is a watershed moment. For the first time, shame is being shifted away from the woman.

The comments by Nirbhaya's father resonated with Jordan, who had already felt the urge to go public when she attended a rally in Kolkata.

"I hid my face for so long, fearing humiliation," Jordan told FoxNews.com. "But then I thought, 'why should I hide? It is not my shame.'"

It is inside one of the new, fast-track courtrooms where Jordan, 38, relives her terror in the hope that she will win justice, not only for herself, but for other victims. Being Suzette Jordan instead of the 'Park Street rape victim' gave her the strength to endure what she calls the horrific journey of justice.

"Taking on indifference and stigma is tough, but when I saw the reactions to Nirbhaya, I felt there is hope for us," she said.

Jordan remembers being victimized all over again when she went to the police. Officers interrogated her for five hours before they filed her complaint. It took eight days more for a government doctor to do a medical exam, which still haunts Jordan.

"I was stripped naked," she said. "They probed me, splayed my legs, did that sick two-finger test that all raped women have to endure."

But a powerful reform movement is under way in India, with the public demanding a new approach to rape cases at all phases. India's more than 70,000 newspapers have been near universal homicide number condemning systemic inefficiencies in preventing and investigating crimes. On online forums, social media and on the street, people have decried the hesitation of cops to accept complaints, their insensitivity toward rape victims, and the slow grind of a patriarchal bureaucracy that has long let perpetrators go scot free.

In 2012, out of about 100,000 rape cases, only 14 percent saw verdicts. And in only a small number of cases -- 3,563 -- did defendants get convicted.

Despite parliament's reforms, which also criminalized acid attacks, stalking and voyeurism and removed the legal protections for accused public servants, many regressive clauses remain. The law remains silent on marital rape. It still gives legal immunity to security forces accused of rape, and does not recognize sexual assault of men and transgendered persons.

Moreover, the main challenge remains: How can sexual violence be http://www.earlyamerica.com/freedom-documents/u-s-constitution/ prevented? The reasons underlying rape -- patriarchy, chronic violence, inequality -- seem exhausting and insurmountable.

In July in Bangalore, when a 9-year-old was raped by a neighbor, her mother's first thought was to think that it must happen to girls everywhere. The mother, who wished to withhold her name, is also abused on a regular basis by her husband. "I get beaten at least once in two days," she said. "If I go to the police, they'll say it's a personal problem."

None of it, however, is personal. Looking for information about ? these 2015 car accident personal injury attorney reviews will give you some good insights.Indian women have always known that the threat of sexual violence exists in every sphere -- at work, on the streets, even at home. Child abuse, acid attacks, dowry-related deaths, and caste-violence are chronic. The police reaction is often bizarre.

A family in rural Jindh in the northern state of Haryana recently sought to report the rape and murder of their 20-year-old daughter. On Aug. 24, the parents found her body in a field, tied to fence wire. There were witnesses to the rape, yet the police say it was a suicide, and the local hospital bizarrely says she died of mosquito bites.

The father, Surat Singh, alleges that the police, who belong to the Jat upper caste, are shielding the accused, who are from the same community.

"It is because we are Dalit," said Singh. Residents from his village are now staging a demonstration near the police station, demanding justice. "I have hope that someone will pay attention," says Singh. "I shudder to think of the day when even this support will be gone."

As more sexual assaults are reported, it is clear that none can be seen in isolation. When arrested, the four boys accused of raping a photojournalist in Mumbai admitted to having raped three women from their slum before. They had not expected to get caught selection of grand jury time either.

As prominent columnist Jay Mazoomdar wrote in Firstpost, "Every assault that goes unpunished anywhere is an encouragement to rapists everywhere. It is really all or nothing -- no woman will ever really feel safe if another does not."

As for Jordan, who sits in court, stunned at the irrelevant details she is asked for, only one thought strengthens her.

"I think of the other women my rapists will surely rape if I don't put them in jail now," she said. "My fight is their fight, too. Your own experience makes you want to watch out for other women."

http://www.foxnews.com/world/2013/09/10/india-perceptions-rape-shift-after-high-profile-cases/

2015PreventingDrunkDriving

Surprising Facts about Penis Health and Aging

Growing older is one of life's great inevitabilities. As the years tick by, the cells that make up the body slowly age, bringing on a gradual change in one's overall appearance and ability to function. Muscles aren't as defined as they once were, skin is not as tight, and things just don't work in the same way they used to. Even still, a few Aggravated Dui candles on the birthday cake doesn't mean that a man can't enjoy his favorite activities, provided he takes adequate care of himself. But penis care is one area of the aging body that men tend to overlook. Learn more about how a man can preserve his penis health so it acts as young as he feels on the inside.

4 Surprising Ways the Penis Ages

The male hormone testosterone is one of the driving forces behind a man's sexual function. As levels of this hormone decline as a natural result of aging, a man can expect several changes to occur down there. Some of these changes may be expected, and others may be a big surprise.

1) It shrinks: Most guys will be very unhappy to learn that the penis does actually shrink over time. Luckily, in some cases, this can be prevented - and even reversed. One of the main reasons for a shrinking soldier is the accumulation of a fat pad on the lower abdomen; the fat actually grows around the penis, making it appear shorter, as the base of the shaft is now hidden. Losing the abdominal weight will, in fact, make the penis appear larger. Unfortunately, there can also be some shrinkage that a man can do nothing about, and over time the penis may appear smaller in both length and girth. The apparent cause of Dwi Attorneys size reduction is the buildup of plaque, or inelastic scar tissue surrounding the erectile chambers. This prevents the penis from reaching its original size during an erection and can cause a slight curvature to the firm manhood, as well.

2) It changes colors: No, nothing dramatic like green or orange, but the penis does often undergo a subtle shift in color as it ages. As circulation gradually diminishes, the purplish color often seen in the head of the penis (the product of an ample supply of blood) fades along with it. The head may take on a more natural fleshy color and match the rest of the goods, particularly when in a flaccid state.

3) It goes bald: It is no secret that as a man ages, he is more prone to baldness - sadly, the same is true for the rest of his body hair. As testosterone declines, a man's pubic hair begins to thin out - good news for men who Driving Under The Influence Of Drugs Penalties a shaved sac, bad news for those who pride themselves on a thicket of hair. Drinking And Driving Punishments balding effect may also reduce chest, back and armpit hair.

4) It becomes less sensitive: Being unable to achieve an erection, or orgasm for that matter, is a bummer for any man - not to mention for his partner. One of the contributing factors to this occurrence is a reduction of sensitivity. Learn what to do during a Truck Accident situation. In case you're looking for some information on Personal Injury Lawyer New York visit www.TruckAccidentGuide.net now!Simply put, if the penile nerves become slightly damaged, as they tend to do after years of masturbating and sex, the sensation is not the same as it once was; therefore, it is more difficult for the penis to reach a state of arousal.

Keeping the Penis Youthful



While these issues can affect any man, and probably will, there is no reason to give in to the inevitable without a fight. Both the young and the young at heart can take steps to keep the little guy spry and responsive. Eating https://www.gov.uk/speeding-penalties right, exercising, drinking plenty of water and allowing time to relax and de-stress are all essential in this respect. In addition, daily use of a penis health formula (health professionals recommend Man 1 Man Oil) can help keep the penis healthy and youthful for many years to come. Men should choose a formula that contains nutrients like acetyl L carnitine (to improve sensitivity); alpha lipoic acid (to reduce wrinkles); and L-arginine (to increase blood circulation to the area) for maximum health of the penis. All penises will naturally age, but with a little help, some can simply age better than others.

Author's Bio: 

visit www.man1health.com for more information about treating common penis health problems, including soreness, redness and loss of penis sensation. John Dugan is a professional writer who specializes in men's health issues and is an ongoing contributing writer to numerous online web sites.

http://www.selfgrowth.com/articles/surprising-facts-about-penis-health-and-aging-shrinkage-hair-loss-color-change-and-more

2015PreventingDrunkDriving

Minnesota jury convicts Final Exit group of assisting 2007 suicide | Reuters

MINNEAPOLIS A jury on Thursday found the national right-to-die group Final Exit Network guilty of assisting a Minnesota woman's suicide in 2007 and interfering with a death scene, prosecutors said.

Sentencing has been scheduled for August in the case stemming from the suicide of Doreen Dunn, 57, who authorities said died by helium asphyxiation with two Final Exit group members present in her home. The convictions carry maximum fines totaling $33,000.

The Dakota County jury deliberated less than two hours before reaching its verdict, which a Final Exit attorney said would be appealed.

"Final Exit Network has been convicted solely for exercising its First Amendment-protected right to freedom of speech," attorney Robert Rivas said in a statement.

Prosecutors had claimed Final Exit members were at Dunn's home and cleaned up after the suicide. Dakota County Attorney James Backstrom said the network's action was "not only legally wrong it is morally reprehensible."

"We are pleased to have brought this organization to justice for these crimes," Backstrom said in http://www.bibliotecapleyades.net/sociopolitica/master_file/newstatesconstitution.htm a statement.

Dunn, who lived in a Minneapolis suburb, was not terminally ill but had suffered from chronic pain since a medical procedure how is the grand jury selected than a decade before her death, which was originally attributed to coronary artery disease.

The death investigation was reopened in 2010 when Georgia investigators told police Dunn had become a member of the organization in the months before her death.

Authorities said Dunn had numerous communications with various members of Final Exit before her death court sentencing process a grand jury in May 2012 indicted the group and four of its members on various charges of assisting Dunn's suicide.



None of the individuals indicted stood trial. Former medical director Dr. Looking for information about ? sentence for mandatory 2015 work injury claim reviews will give you some good insights.Lawrence Egbert, who was present when Dunn died, was granted immunity to testify for prosecutors while the other member present at Dunn's death has since died.

Charges were dismissed against a third member and a fourth was excused from the trial due to ill health.

Final Exit Network is a non-profit organization that has said its members can be present but do not encourage, provide the means for or assist in a person's suicide.

Minnesota is not among the states where assisted suicide is legal. Physician-assisted suicide is legal in Oregon, Washington, Montana and Vermont.

(Reporting by David Bailey; Editing by Bill Trott)

http://www.reuters.com/article/2015/05/14/us-usa-minnesota-finalexit-idUSKBN0NZ2AI20150514

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