Safety and Risks: November 2006 Archives

FDA Safety Changes: CNS Stimulants and Roferon A


roferon aNovember 29, 2006 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise that use of central nervous system stimulants may increase the risk for cardiovascular events and exacerbate psychotic symptoms in certain patients and that chronic use may cause temporary suppression of growth rate in children. Also, interferon-alfa-2a [recombinant] subcutaneous injection may be linked to potential risks for severe infection and pancreatitis.

CNS Drugs May Potentiate Risk for Sudden Death

The FDA approved safety labeling revisions in August for dexmethylphenidate HCl tablets and extended-release capsules (Focalin and Focalin XR, made by Novartis Pharmaceuticals Corp), methylphenidate HCl extended-release capsules (Metadate CD, made by UCB Pharma, Inc), methylphenidate chewable tablets/oral solution (Methylin, made by Mallinckrodt), and methylphenidate tablets, sustained-release tablets, and extended-release capsules (Ritalin, Ritalin SR, and Ritalin LA, made by Novartis Pharmaceuticals Corp).

Private HMOs cost more to Medicare


medicare card CHICAGO (Reuters) - Private insurers in the Medicare insurance program were paid 12.4 percent more by the government than the health care provided would have cost under traditional Medicare, a report released on Thursday said.

Payments to private insurers were $922 more per enrollee in 2005 than they would have been to the government-run program, the report by the nonprofit research group the Commonwealth Fund said.

Private managed-care companies have taken a bigger role in Medicare, the health insurance program for 43 million elderly, after recent changes pushed by President George W. Bush and the Republican-led U.S. Congress.

Ob/Gyn Group Urges Pregnant Women to Shun Paxil

paxilHealthDay News -- A group representing America's obstetricians is recommending that women avoid the antidepressant Paxil if they are pregnant or planning on becoming pregnant, due to a potential heightened risk for birth defects.

The American College of Obstetricians and Gynecologists (ACOG) also cautioned that treatment with other antidepressants should be considered on a case-by-case basis.

ACOG's Committee on Obstetric Practice "recommends that treatment with all SSRIs [selective serotonin reuptake inhibitors] or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine [Paxil] use among pregnant women or women planning to become pregnant be avoided, if possible," read the statement, which is in the December issue of Obstetrics & Gynecology.

FDA Questions Celebrex for Kids' Arthritis


celebrexPfizer Inc. may fall short in convincing federal regulators that its painkiller Celebrex should receive expanded approval to treat children with a devastating form of arthritis, according to documents released Tuesday.

Pfizer wants Food and Drug Administration approval to sell Celebrex as a treatment for juvenile rheumatoid arthritis, or JRA, which affects as many as 60,000 U.S. children. The disease causes painful joint swelling and can affect growth and development.

However, an FDA review of the New York company's application questions whether the drug works for the pediatric disease. The FDA approved the drug for use in adults with osteoarthritis and rheumatoid arthritis in 1998.

Painkillers May Threaten Power of Vaccines


drugsWith flu-shot season in full swing and widespread anticipation of the HPV vaccine to prevent cervical cancer, a new University of Rochester study suggests that using common painkillers around the time of vaccination might not be a good idea.

Researchers showed that certain nonsteroidal anti-inflammatory drugs (NSAIDs), also known as cyclooxygenase inhibitors, react with the immune system in such a way that might reduce the effectiveness of vaccines.

The research has widespread implications: study authors report that an estimated 50 to 70 percent of Americans use NSAIDs for relief from pain and inflammation, even though NSAIDs blunt the body's natural response to infection and may prolong it.

pfizerVANCOUVER, BRITISH COLUMBIA--(CCNMatthews - Nov. 28, 2006) - A major national research project, co-led by Drs. Bruce Carleton and Michael Hayden, to improve drug safety for children, today received a major contribution of $500,000 from Pfizer Canada Inc. The project, named Genotype-Specific Approaches to Therapy in Childhood (GATC), receives major funding from a Genome Canada/Genome BC-sponsored research program and is led from two research centres within the Child & Family Research Institute (CFRI) at BC Children's Hospital.

A failure of modern medicine is the debilitating and lethal consequences of adverse drug reactions (ADRs) which rank as one of the leading causes of death and illness in North America. Children are at a greater risk for severe ADRs, yet there remains a lack of understanding of their causes due in part to an inability to conduct pediatric patient studies of similar rigour and scope as in adult populations. The goal of GATC is to promote the health and well-being of Canadian children and of the global pediatric community by developing cost-effective interventions to reduce life-long disabilities and deaths caused by severe ADRs. The project will identify pediatric patients experiencing ADRs, collect DNA samples, apply genomics-based technologies to identify ADR-associated genetic markers and help predict and prevent drug toxicity.

Warning Issued on Dangers of Methadone


methadonePeople starting treatment with methadone have died and suffered life-threatening side effects, health officials said Monday in warning of the dangers of overdosing on the painkiller.

Overdoses of the increasingly popular narcotic can cause slow or shallow breathing and dangerous changes in heart beat that patients might not feel, the Food and Drug Administration said.

Those side effects, including reports of deaths, have been seen in patients starting methadone treatment for severe pain or who switched to the drug after using other strong narcotic pain relievers, the FDA said in a public health advisory.

The FDA warned that methadone only provides pain relief for four to eight hours, but can linger in the body for eight to 59 hours. That can lead patients to take more of the drug before it has been eliminated by the body, causing the drug to build up in the body to toxic levels, the FDA said.

Pfizer drug has history of risks


celebresWASHINGTON -- Despite Celebrex's well-documented link to higher heart risks, Pfizer Inc. wants permission to sell its painkiller to treat children as young as 2 who have arthritis.

Even as critics call for the drug to be removed from the market, Food and Drug Administration advisers will meet Wednesday to consider the company's request to expand Celebrex use.

Celebrex was the first of a class of new-style painkillers, called cox-2 inhibitors , approved in December 1998, and it is the last one to remain on the market. The drugs were designed to relieve pain without causing the stomach distress associated with other treatments, but they have been plagued by safety concerns. Merck & Co. pulled Vioxx from the market in 2004 after its studies showed the painkiller doubled the risk of heart attacks and strokes. Merck now faces more than 20,000 Vioxx lawsuits. Pfizer, under pressure from the FDA, last year halted sales of another cox-2 inhibitor, Bextra , because of heart risks and potentially fatal skin reactions.

Responsible Businesses, Healthy Places To Work?

businessA study into the relationship between an organisation's understanding and use of corporate social responsibility (CSR) and its health and safety practices has revealed problems within the small- and medium-sized (SME) business sector.

A report by Dr Stavroula Leka and Johanna Churchill from the Institute of Work, Health and Organisations at The University of Nottingham claims there is a lack of knowledge in the areas of both CSR and occupational health and that leadership can be a considerable barrier to the prevention of health and safety problems.

ADAPT Safety Results Now Published

PLoSA paper appearing this week in the Public Library of Science journal PLoS Clinical Trials presents findings from a large National Institutes of Health sponsored trial regarding the cardiovascular and cerebrovascular safety of two non-steroidal anti-inflammatory drugs (NSAIDs), celecoxib and naproxen. The trial was initially conducted to test whether these drugs might prevent or delay the onset of Alzheimer's disease.

The paper describes the occurrence of adverse cardiovascular events, particularly heart attacks and strokes, in some 2500 elderly people who took celecoxib, naproxen, or placebo for up to 3.5 years while participating in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). The cardiovascular risk of NSAIDs is currently a controversial and hotly debated topic. One such drug, the selective COX-2 inhibitor rofecoxib (Vioxx) has been withdrawn from the market due to concerns about its cardiovascular safety. There is also debate over the safety of other selective COX-2 inhibitors, including celecoxib. Not much data from randomized trials exists on the long-term safety of non-selective, or "traditional", NSAIDs, such as naproxen.

FDA seeks drug safety budget boost from pharma

FDAThe US Food and Drug Administration (FDA) and the pharmaceutical industry are in strong negotiations to decide how much drug companies will pay the agency to review new drugs from the end of next year, when the current law expires.

Last week, the FDA's deputy commissioner Scott Gottlieb said that pharma companies should contribute additional funds so the agency can study the drugs' safety once they reach the market.

The US drug industry is now negotiating the fourth version of the Prescription Drug User Fee Act (PDUFA) with the regulator – the outcome could change radically the landscape for pharma companies.

Until now, user fees paid by firms have primarily been used to review the safety and efficacy of new drugs before they are approved to be sold on the market.

Judging the Safety of Aprotinin


trasylolby Dennis T. Mangano, Ph.D., M.D.

I was troubled by the recent, near-unanimous decision of the Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee publicly advocating the safety of aprotinin1 — despite considerable evidence to the contrary,2,3,4 including our recent study2 and the FDA's own initial 1993 warning regarding "kidney toxicity."5 We learned after the Advisory Committee's meeting of newly disclosed records of 67,000 patients, yielding data that were consistent with our warnings (renal failure, stroke, and heart failure)2 and that were inconsistent with the positions of the committee and Bayer.1,6

In defending the committee's decision, Dr. Hiatt makes allegations in this issue of the Journal regarding our "transparency" (FDA access to our data).7 In fact, there is no question that our independent, nonprofit research groups (the Ischemia Research and Education Foundation [IREF] and the Multicenter Study of Perioperative Ischemia [McSPI] reseasrch group) made every effort to have the FDA review in detail all of the source and derivative data from our study2 and all associated documentation and operating procedures.

Covance invests to gain edge in drug safety testing

covanceCovance has invested in mass spectrometer technology that it hopes will give it the edge over other contract research organisations (CROs) in the safety testing of new drug candidates.

The company said it was the first CRO to acquire the technology, which “is fast becoming a new standard for qualitative mass spectrometry that enables faster, more sensitive and more reliable detection and identification of compounds in complex mixtures than existing hybrid time-of-flight systems.”

The Thermo LTQ OrbitrapT is said to produce accurate mass data on drugs and metabolites in almost half the time of other mass spectrometers as well as facilitating metabolism evaluation of a drug candidate at a much earlier stage of the development process.

US judge rejects national class-action lawsuit over Vioxx

vioxxNEW YORK (AFP) - A US federal judge refused to allow a class-action lawsuit to proceed against Merck for health problems linked to its Vioxx pain medication, in a major victory for the pharmaceutical giant.

Judge Eldon Fallon, asked by an interstate judicial panel to consider how to handle the thousands of lawsuits filed over Vioxx, said the cases did not meet the criteria for a national class action suit, where one court would hear the case for all plaintiffs.

"While the majority of plaintiffs in this case allegedly suffered either a heart attack or stroke as a result of ingesting Vioxx, the extent of each plaintiffs subsequent injuries varies widely," he said in a 25-page decision.

Beta Agonists May Alter the Immune System

beta agonists in inhalers New research at Wake Forest University School of Medicine suggests that certain inhaled asthma medications – as well as similar chemicals our bodies produce during times of high stress – may worsen diseases such as asthma , heart failure and lupus that involve inflammation.

The scientific team led by Raymond Penn, Ph.D., and Matthew Loza, Ph.D, found that beta-agonists, such as those used in the treatment of asthma, increase the accumulation of type 2 T cells, a type of white blood cell that participates in immune system defense mechanisms. In certain diseases such as asthma and lupus, an over-reactive type 2 T cell response occurs and is believed to contribute to the disease.

“Inhaled beta-agonists are very effective in opening up airways and allowing asthmatics to breathe, but their ability to address the underlying inflammation that causes most asthma has been debated for years,” said Penn, an associate professor in the Department of Internal Medicine and the Center for Human Genomics.

FDA OKs Return of Silicone Breast Implants

silicone breast implantsHealthDay News -- Despite decades of controversy over the dangers of silicone breast implants, the U.S. Food and Drug Administration on Friday lifted a 14-year ban on their commercial use.

The FDA gave approval to two companies, Allergan Inc., of Irvine Calif., and Mentor Corp, of Santa Barbara, Calif., to market the implants to all women aged 22 and older. Until now, women have only been allowed access to the implants as part of research studies.

"In 1992 the FDA required manufacturers to stop selling silicone gel-filled breast implants because of lack of data to support marketing approval," Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said during a late afternoon news conference.

Naproxen Painkillers May Pose Heart Danger


naproxen WASHINGTON -- Researchers looking at the safety of various arthritis and headache remedies said on Thursday they had found some more evidence that the popular analgesic naproxen may cause heart problems.

The researchers themselves cautioned about reading too much into their findings, and outside experts discounted them.

Nonetheless, the researchers said they thought it was important to present their evidence to help experts sort out what the real dangers are.

Pfizer seeking to have Celebrex OKd for kids


celebrexCelebrex - the only Vioxx-like drug still on drugstore shelves - could soon be sold specifically as a treatment for rheumatoid arthritis in children if the Food and Drug Administration approves a Pfizer request to do so.

The FDA has already approved Celebrex (celecoxib) to fight pain and inflammation but not specifically for use in children. Only 20 percent to 30 percent of FDA-approved drugs are specifically labeled for pediatric use.

But now Manhattan-based Pfizer is seeking FDA approval to market Celebrex specifically in children 2 years and older who have rheumatoid arthritis.

Results mixed on Merck's new painkiller

arcoxiaCHICAGO - The first published studies of Arcoxia, the drug that Merck & Co. hopes will take the place of its withdrawn painkiller Vioxx, are getting mixed reviews from doctors, some of whom say the results do not make a case for the medication's approval.

The critics cite not just Arcoxia's side effects but also that Merck tested it against diclofenac, an older painkiller known to raise heart risks. A fairer comparison would have been to a medicine that does not do that, such as naproxen, sold as Aleve, they say.

"The development program for Arcoxia is fatally flawed," said Dr. Steven Nissen, a Cleveland Clinic cardiologist who formerly headed the Food and Drug Administration's cardiac drug advisory panel. "My advice to the FDA is that they should not approve this drug."

Lethal pill deaths spark manhunt


death from drugsPolice are hunting for a man, whom they believe gives people a lethal blend of two anti-depressant prescription drugs, following the deaths of two men in Sydney.

A third possible victim might have survived.

Authorities are describing the deaths as "suspicious", rather than murder.

The combination of the drugs can bring on a potentially fatal condition referred to as serotonin syndrome, which can cause blood-clots in the brain, kidney failure, hallucinations and comas.

Students abusing 'Smart Drugs' to keep grades up

young studentsFor years, students pulling all-nighters have gulped coffee to stay awake. But now growing numbers are popping pills -- and not to party.

CBS 2's Medical Editor Mary Ann Childers reports it's to help them study. We have hidden the faces, and changed the names and voices of students we talked with about smart drugs.

Adderall, Concerta and Ritalin are widely used to treat children with attention-deficit hyperactivity disorder. They are also being abused by tens of thousands of students who don't have ADHD, but who, like college freshmen Ashley and Jason, want an academic edge.

Both say they began taking Adderall in high school.
painkillers capletsThe FDA today announced a recall of about 11 million bottles of store-brand acetaminophen 500-milligram caplets.

Those caplets are over-the-counter drugs for pain relief and fever reduction. They're sold by about 130 companies, including Wal-Mart, CVS, and other drug stores, grocery stores, and wholesalers.

The recall is due to "small metal fragments found in a small number of these caplets," states an FDA news release.

The fragments range in size from "microdots" to 8-millimeter pieces of wire, according to the FDA.

The FDA and the caplets' maker, Perrigo Company of Allegan, Mich., are investigating how those metal fragments got into the caplets.

So far, no illnesses, injuries, or consumer complaints have been reported to the FDA or Perrigo, according to the FDA.

Novartis pain drug battles Vioxx stigma


prexige logoNEW YORK ( -- Novartis plans to bring a new arthritis painkiller to the U.S. market, but analysts say its similarity to the disgraced drug Vioxx could kill its chances of becoming a billion-dollar blockbuster.

The Swiss drug giant Novartis AG (up $0.32 to $61.55) said Tuesday that its painkiller Prexige was given a green light in the European Union for the treatment of arthritis. Novartis plans to "resubmit" the drug to the Food and Drug Administration in 2007, following the agency's request for more information in 2003.

Compared to Vioxx from Merck & Co., Inc., (up $0.33 to $46.14, Charts) Prexige has a better profile with regard to heart attack and stroke risks. Nonetheless, the drug is a member of the Cox-2 inhibitor class of drugs -- the same as Vioxx -- and could have a hard time winning the approval of American doctors and patients, not to mention the FDA.

"Doctors will be afraid to use this drug and ultimately that's what limits its potential," said Gbola Amusa, analyst for Sanford C. Bernstein. "Even when it's approved, doctors will see a safety issue with the drug and not use it as much."


Researchers Apologize for Disclosure Failure on Drug Study

athritisHealthDay News -- The failure of researchers to fully disclose pharmaceutical-industry connections in a study of drugs used to treat rheumatoid arthritis has resulted in a letter of apology to the Journal of the American Medical Association.

However, everyone involved is quick to note that both the findings of the study and the methods used were sound. And while the exact meaning of the findings is the subject of debate, there appears to be no question of the validity of the science involved.

The original study appeared in the May 17, 2005, issue of JAMA. In that study, Dr. Eric L. Matteson, a professor of medicine at the Mayo Clinic, and colleagues looked at the risk of cancer among patients taking infliximab (Remicade, Enbrel) and adalimumab (Humira) for rheumatoid arthritis.

These drugs are tumor necrosis factor-alpha blockers (TNFs). TNF blockers bind to tumor necrosis factor-alpha, making it inactive, reducing inflammation and joint damage.

Preventing Costly Missteps In Drug Development


computer and drug researchThe script for one of the most dreaded scenarios in new drug development reads like this: Company A sinks several hundred million dollars into putting a new drug onto pharmacy shelves. Only then do serious side effects appear, and force withdrawal of that drug from the market.

Researchers in India now are reporting development of a new and more accurate method for predicting toxicity in the very early stages of drug development.

Nagasuma R. Chandra and colleagues describe the computer technique in the November/December issue of the ACS's bi-monthly Journal of Chemical Information and Modeling. They also report on its use in predicting with high accuracy one form of toxicity - a heart rhythm disorder that forced withdrawal of the popular antihistamine terfenadine (Seldane).