Safety and Risks: December 2006 Archives

Researchers from major pharmaceuticals, Swiss-based computational biology firm Genedata and European Commission (EC) representatives met recently in Dublin for the Second General Assembly of InnoMed PredTox consortium. InnoMed PredTox is a joint Industry, Academic and EC collaboration to improve drug safety testing.

Tasked with exploring the molecular basis of drug-side effects, InnoMed PredTox is an ambitious project involving leading European pharmaceutical companies, academic research institutes and Genedata.

The gathering in Dublin met for an update on general progress over the last nine months and to discuss the consortium’s newly launched central data sharing portal. Biomolecular data from more than 20 laboratories is fed into a joint database, which is based on Genedata’s Expressionist platform.

December 22, 2006 — The US Food and Drug Administration (FDA) has approved safety label revisions to advise of the expected similarity of levetiracetam's safety profile in patients with juvenile myoclonic epilepsy compared with partial-onset seizures; the rare risk for cardiac arrest in patients receiving ropivacaine HCl injection for the purposes of anesthesia or peripheral nerve blockade; and the risk for dental and periodontal disorders associated with use of ribavirin in with concomitant interferon therapy.

Levetiracetam (Keppra) Linked to Somnolence and Behavior Abnormalities in JME Patients

On August 15, the FDA approved safety label changes for levetiracetam tablets and oral solution (Keppra, made by UCB, Inc) to advise of risks associated with their use as adjunctive therapy for myoclonic seizures in patients aged 12 years and older with juvenile myoclonic epilepsy (JME), a new indication.

By DAN CHILDS, ABC News Medical Unit

Calls for stronger warning labels for certain over-the-counter (OTC) medications question the safety of products that are a fixture in the medicine cabinets of nearly every American household.

On Tuesday, the Food and Drug Administration proposed stronger warning labels for acetaminophen, widely known by the brand name Tylenol, and the common class of pain relievers known as nonsteroidal anti-inflammatory drugs, or NSAIDs. This group includes ibuprofen and aspirin.

Considering the familiarity of these medicines, many consumers assume they are safe.

FDA closes some of its labs. I understand that restructuring is focused on optimizing resources and reducing expenses. Business as usual. However, this article says that "the group believes the closures could slow the response to a bioterrorism attack.."

What bioterrorism attack? This is not the first time media is letting these two words slip into the news. What is the purpose of this sentence - to create a fear amongst americans to use their response as a lever in some politic game, or what?

Do you want to speed up the response to a "bioterrorism attack"? Ban the fast food shops.

Read the article below.. 

This week, the FDA updated its quarterly reporting on adverse events. It is a bit of a complicated mess to work your way through. But there are other ways to look at adverse events and given that there have recently been a few drugs experiencing well-publicized adverse events, it seemed like a good subject to explore.

The FDA has a Freedom of Information Act [FOIA] office that processes requests for information. Among the information that can be requested is a printout of the adverse events for a particular drug, or even those related to a particular company. When submitting a FOIA, you can specify any parameters. The only thing you have to do is (1) be patient - it used to take about 6 weeks, but it does vary, and (2) pay for it, but it is not exorbitant and price depends on how lengthy your research is. Depending on what you ask for, you also may need storage - the reports are computer sheet printouts that can go on for pages, so be careful what parameters you choose. If you choose too broadly, you can wind up with a LOT of unwanted information and paper.

ROCHESTER, N.Y., Dec. 21 /PRNewswire/ -- U.S. adults are calling for information on and oversight of the pharmaceutical industry. According to a recent Harris Poll, close to three out of four (71%) adults believe that it is very or highly important that pharmaceutical drugs, even after they are made available to the public, remain under close review by the U.S. Food and Drug Administration (FDA) and drug companies. An additional one in five (20%) says that it is important that the drugs remain under close review. Only nine percent say it is only somewhat or not very important. Of note, the FDA currently has a process in place to conduct post-marketing surveillance of drugs (however, respondents were not asked whether or not they are familiar with this).

Furthermore, many Americans are demonstrating consumerism by proactively seeking out information on drug safety. About four in 10 (41%) indicate that they always or often seek information on drug safety for themselves and/or family members. One-third (35%) say they sometimes seek out information on drug safety and just one-quarter (24%) rarely or never seek out this information.

A powerful painkiller is raising red flags in western Wisconsin after an increase in the number of overdoses. There have been a string of deaths from Fentanyl overdoses. Some have been intentional, some were not.

In September, Dr. Susan Momont was found dead in her Eau Claire home. Her husband has now been charged with providing the Fentanyl that caused her death.

The St. Croix County medical examiner says three people have died in his county since this spring. Last week, the Chippewa County district attorney said a man there died from an overdose, which may have been a suicide.

Federal health officials on Tuesday proposed sterner warning labels for acetaminophen, aspirin and ibuprofen, again cautioning millions of Americans who take the nonprescription pain relievers regularly of potentially serious side effects.

The over-the-counter drugs remain safe and effective when used as directed, the Food and Drug Administration said. However, overdoses of acetaminophen can cause serious liver damage, even death, the FDA said.

For aspirin, ibuprofen and other nonsteroidal anti-inflammatory drugs, there is a risk of gastrointestinal bleeding and kidney injury even when patients take the correct dose. The drug are linked to thousands of deaths a year. The FDA said the risk is rare when compared to the number of patients who take the drugs.

Eli Lilly encouraged primary care physicians to use Zyprexa, a powerful drug for schizophrenia and bipolar disorder, in patients who did not have either condition, according to internal Lilly marketing materials.

The marketing documents, given to The New York Times by a lawyer representing mentally ill patients, detail a multiyear promotional campaign that Lilly began in Orlando, Fla., in late 2000. In the campaign, called Viva Zyprexa, Lilly told its sales representatives to suggest that doctors prescribe Zyprexa to older patients with symptoms of dementia.

A Lilly executive said that she could not comment on specific documents but that the company had never promoted Zyprexa for off-label uses and that it always showed the marketing materials used by its sales representatives to the Food and Drug Administration, as required by law.

The president of Alliance for Human Research Protection’s explains the importance of informing the public.

Just as Vera Sharav sits down to talk about the lack of government oversight of the drug industry, the phone rings. She jumps up to answer it, and after listening patiently for a few minutes, she starts talking about Prozac, warning the caller that U.S. consumers don’t always get the same detailed health warnings about pharmaceuticals as residents of some other countries. After hanging up, Sharav, president of the advocacy group Alliance for Human Research Protection, gets right to the point.

“We’ve got a major crisis in America now,” Sharav says. “There is carnage going on. There are thousands of preventable deaths every year.” Approval of a drug by the U.S. Food and Drug Administration implies that a drug is safe to market to consumers, but Sharav asserts that the FDA’s assurances are not based on good science.

TRENTON, N.J. - A former vice president at two Johnson & Johnson subsidiaries claims in a lawsuit he was fired for seeking recalls of numerous faulty products, including the Ortho Evra birth control patch, itself the subject of at least 1,000 product liability suits.

New Brunswick, N.J.-based Johnson & Johnson, one of the world's biggest drug and medical product makers, said yesterday the ex-executive was fired for inappropriate conduct.

In his civil complaint, Dr. Joel S. Lippman alleges he was unlawfully terminated on May 15, after working for Johnson & Johnson for 15 years, because he repeatedly complained about product safety problems and urged several be recalled or not launched. Lippman declined to be interviewed.

The U.S. Food and Drug Administration needs to more closely regulate direct-to-consumer advertising of prescription drugs, the Government Accountability Office said on Thursday.

It found the agency moved too slowly in reviewing ads on products ranging from impotence remedies to incontinence pills, and too slowly in trying to stop misleading ads.

"We believe that regulatory letters must be issued more quickly," the GAO, the investigatory arm of Congress, said in its report.

The Health and Human Services Department, which oversees the FDA, said the report was unrealistic, and meeting the GAO's recommendations "would require vastly increased staff to essentially review every piece in detail."

SILVER SPRING, Md., Dec. 14 (UPI) -- A Food and Drug Administration advisory committee will decide Friday whether to recommend that a widely used but controversial antibiotic be removed from the market.

The drug, known as Ketek, is used to treat respiratory tract infections such as bronchitis, sinusitis, and pneumonia. U.S. Doctors have written an estimated 6 million prescriptions for the drug since it was approved in April, 2004.

But FDA is revisiting that approval in two days of expert hearings Thursday and Friday because of reports suggesting the drug could carry a higher risk of liver failure and other dangerous side effects than similar antibiotics.

CAMBRIDGE, Mass — Vertex Pharmaceuticals Inc. said Wednesday a safety analysis of its developing hepatitis C drug VX-950 showed 9 percent of the patients involved dropped out of the program because of adverse events including gastrointestinal disorders and rash.

The news sent shares of Vertex fell 62 cents to $38.78 in morning trading on the Nasdaq, following a drop in premarket trading.

The midstage study involved 250 patients, with the current interim data involving 74 patients for whom data was available at 12 weeks. Patients were given either the drug, called telaprevir, or placebo in combination with ribavirin. The safety study results showed that 9 percent discontinued treatment because of adverse events, with rash being the most common, compared with 3 percent of the patients taking placebo.

GAITHERSBURG, Md.--(BUSINESS WIRE)--GenVec, Inc. (Nasdaq: GNVC) announced today that an independent data safety monitoring board (DSMB) has completed a planned interim analysis of safety data from the ongoing Phase II/III clinical trial with TNFerade™ in locally advanced pancreatic cancer. In addition to its recommendation that the trial continue, the DSMB supported the use of endoscopic ultrasonography (EUS) as an alternative to percutaneous tumor administration. GenVec has provided its interim safety data to the U.S. Food and Drug Administration (FDA) and is waiting for final clearance to move forward with EUS administration.

The Phase II/III clinical trial, known as PACT, is a multi-center, randomized and controlled study of 330 patients, designed to evaluate the safety and efficacy of TNFerade plus standard of care, versus standard of care alone (SOC) in patients with locally advanced pancreatic cancer. This interim evaluation was based on data from 40 patients, 25 of whom received standard of care plus TNFerade.

The FDA said Wednesday it planned to expand warnings on up to a dozen antidepressant medications following studies suggesting the drugs raise the risk of suicidal behavior in a wider range of patients than previously thought.

In 2004, the agency ordered "black box" warnings to be added to antidepressant packaging alerting doctors of evidence that the drugs increase the risk of suicidal thoughts and attempts in children and teens under the age of 18. Officials said Wednesday they would now move to expand the warning to include young adults up to age 25.

The warnings apply to selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Paxil, in addition to related drugs including Effexor and Wellbutrin. Officials said the warnings would also likely be included in medication guides distributed to patients

The FDA is telling people not to use the malariamalaria drug quinine for leg cramps, citing potentially deadly side effects.

The FDA issued the advice today and ordered all unapproved drugs containing quinine off the market within 60 days.

Qualaquin, the only FDA-approved quinine drug, can be used to treat certain types of malaria; the new order doesn't change that.

But quinine is also often prescribed to treat leg cramps. That unapproved use is too risky, says the FDA.

Memory Pharmaceuticals Announces Release of Clinical Hold on MEM 3454

MONTVALE, N.J., Dec. 11 -- Memory Pharmaceuticals Corp. today announced that the U.S. Food and Drug Administration (FDA) has completed its review of the investigational new drug application (IND) for MEM 3454 and has informed the Company that the clinical hold on the development of this drug candidate has been released. The Company now plans to commence its previously-announced Phase 2a clinical trial for MEM 3454 in Alzheimer's disease during the first quarter of 2007.

"Memory has worked diligently with the FDA since this trial was placed on clinical hold in October, and we are pleased that we will now be able to move forward with the proof-of-concept trial for this important drug candidate," stated Jim Sulat, President and Chief Executive Officer of Memory Pharmaceuticals.

by Dr. Peter Breggin

On December 13, 2006 the FDA's Psychopharmaceutical Drugs Advisory Committee (PDAC) is meeting in Silver Spring, Maryland to discuss antidepressant-induced suicidal behavior in adults. In 2004 the FDA held similar hearings on children and concluded that antidepressants do in fact cause suicide in humans under age eighteen. A warning has been placed in all antidepressant labels or package inserts.

Now the agency has given advanced notice of its new findings--antidepressants, all of them according to the FDA, cause increased suicidality in young adults. Suicide occurs more than twice as much on antidepressants than on sugar pills in individuals under age 25.

After six members of a Phase I trial of TeGenero’s TGN1412 nearly died, an expert scientific group, headed by Professor Gordon Duff, was convened to investigate the incident and recommend new procedures to increase the safety of future ‘first-in-man’ trials.

The drugs, which passed standard pre-clinical trials, were supposed to subtly “retune” the immune system. Instead they sent the immune system into overload and the members of the trial suffered multiple-organ failure. The effects were so severe that fingers and toes had to be amputated.

The report called for increased communication between the drug developer and the regulatory body before application for Phase I trials. Pre-clinical trial safety information should be submitted to a database to speed-up the process. This should allow the regulators to identify potential concerns and discuss these with appropriate independent specialist experts.

Newswire Today —  Basel, Switzerland, 2006-12-06 - Joint industry/academic consortium InnoMed PredTox met recently in Dublin for a progress report and to discuss the consortium’s newly launched central biomolecular data sharing platform, developed by Swiss-based computational biology firm Genedata.

Researchers from major pharmaceuticals, Swiss-based computational biology firm Genedata and European Commission (EC) representatives met recently in Dublin for the Second General Assembly of InnoMed PredTox consortium. InnoMed PredTox is a joint Industry, Academic and EC collaboration to improve drug safety testing.

Tasked with exploring the molecular basis of drug-side effects, InnoMed PredTox is an ambitious project involving leading European pharmaceutical companies, academic research institutes and Genedata.

The Food and Drug Administration plans to improve the Web portal so that anyone can report adverse drug effects and will try data mining to learn more about any problems with regulated medicines.

The agency, which has been criticized for paying too little attention to prescription drugs after they are approved for sale, also will offer a downloadable software module that doctors and other practitioners can use to report on drugs. The module will work with existing electronic medical records, making reporting easier for those with EMR systems.

Dr. Scott Gottlieb, the FDA’s deputy commissioner for medical and scientific affairs, disclosed those and other information technology tactics in a November speech. Gottlieb did not give a timetable for completing the projects, and FDA spokeswoman Crystal Rice said such questions were premature.

WASHINGTON--(BUSINESS WIRE)--Dr. Stephen Galson, Director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration, led a slate of keynote speakers and panelists from industry, regulatory agencies and academia at Windhover’s 2nd Annual FDA/CMS Summit today. Across the presentations was a common resonating theme of imminent drug safety reform. However, rather than being seen as an obstacle to business, industry executives and regulators suggest the coming discussion presents an opportunity to define a new model of drug development and evaluation for the 21st century.

Executives from MedImmune, Merck and Roche posited that developments in personalized medicine and a focus on value-based healthcare offer a business opportunity on which companies may capitalize. To understand the implications of potential changes to drug safety evaluation, as well as other hot topics, the audience of more than 200 heard from:

BEIJING, Dec. 4 (Xinhuanet) -- More than 6 million people worldwide -- a modern record for any medical device -- were relieved of chest pain or heart attack risk by the insertion of drug-coated stents in their arteries the last few years, but now doctors say their long-term safety is in question.

Unless their patients remain on Plavix, a 4-U.S.-dollar-a-day anti-clotting drug whose long-term safety has not been proven, doctors are worried these stents may raise the risk of life-threatening blood clots months and even years later.

And thousands of others each day who develop new blockages are being treated by doctors no longer sure of what to do. Many are returning to the old metal stents, and some are fundamentally rethinking when to use stents at all and are considering alternatives like bypass surgery or medications.

Pfizer Inc. said Saturday it has cut off all clinical trials and development for a cholesterol drug that was supposed to be the star of its pipeline because of an unexpected number of deaths and cardiovascular problems in patients who used it.

The world's largest drugmaker said it was told Saturday that an independent board monitoring a study for torcetrapib, a drug that raises levels of HDL, or what's commonly known as good cholesterol, recommended that the work end because of "an imbalance of mortality and cardiovascular events."

The news is devastating to Pfizer, which had been counting on the drug to revitalize stagnant sales that have been hurt by numerous patent expirations on key products. It has said it was spending around $800 million to develop Torcetrapib.

WASHINGTON (AP) - Dozens of poor and minority pregnant women were put at risk when they were given dummy pills instead of a drug believed to prevent outbreaks of genital herpes, consumer watchdogs charged Friday.

The researchers defended their work, saying in part the study was to assess the uncertain risks of the drug to the women's fetuses.

In the study, researchers at Parkland Hospital in Dallas gave 170 pregnant women the drug valacyclovir to see if the drug would reduce herpes outbreaks at birth. The virus can be fatal to newborns if infected during delivery.

HealthDay News -- Many Americans, including those with college degrees, have trouble interpreting the instructions on prescription drug labels, a new study finds.

Indeed, only 34.7 percent of the people with lower literacy, grade level or below, interviewed for the study could determine the number of pills to take daily when faced with "take two tablets by mouth twice daily," according to the study report in Annals of Internal Medicine.

And 9 percent of all those interviewed had trouble with the instruction, "take one tablet by mouth once each day."