FDA cites bleeding risk with experimental J&J drug

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Posted on 17th March 2009 by Gordon Johnson in Uncategorized

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Date: 3/17/2009

By MATTHEW PERRONE
AP Business Writer

WASHINGTON (AP) — Federal health officials say a Johnson & Johnson drug helps prevent deadly blood clots in patients getting hip or knee replacement, but it also carries a risk of serious internal bleeding.

Johnson & Johnson and partner Bayer have asked the Food and Drug Administration to approve their once-daily pill, rivaroxaban, as an anticlotting drug to stop blood clots in legs and those that can travel to the lungs. More than 800,000 U.S. patients receive hip or knee replacements each year, and an estimated 40 to 60 percent are at risk of blood clots.

But FDA regulators said in documents posted online Tuesday that the drug carries nearly twice the risk of bleeding of Sanofi-Aventis’ Lovenox, the top-selling blood thinner used by patients receiving orthopedic implants.

On Thursday the agency will ask a panel of cardiology experts to weigh in on the drug’s risks and benefits. The FDA is not required to follow the advice of its panel, though it usually does.

After reviewing four studies with more than 12,000 patients, the FDA said major bleeding occurred in 0.4 percent of patients on the J&J; drug, compared with 0.2 percent of those taking Sanofi’s drug, known chemically as enoxaparin. The drug was Paris-based Sanofi’s biggest product last year, with sales of $3.5 billion.

“The evidence that administration of rivaroxaban could lead to bleeding events in significantly more patients relative to enoxaparin amplifies this safety concern,” states the FDA’s review, posted online Tuesday.

Regulators also voiced concerns about potential risks of liver injury or toxicity, a common side effect with blood-thinning drugs. Bayer and J&J; have proposed that the drug would be used for only two weeks by knee surgery patients and five weeks by hip surgery patients.

But the FDA is concerned doctors could use it for longer periods. The agency will ask its panelists whether there is enough information to gauge the risks of the drug over the long term.

The agency said it asked the companies to develop a lower-dose version of rivaroxaban that could be used by patients with liver or kidney problems. According to the agency, the companies “regarded this modification as unnecessary.”

But a J&J; spokesman said the company “is actively working with the FDA on this issue to assure the best balance of benefit and risk.”

The FDA also said the companies declined to design a risk minimization strategy for their drug, or a plan to help doctors and patients use the drug safely. But the company said it has submitted a number of plans to reduce the drug’s risks, including education and outreach programs.

The agency will have to weigh rivaroxaban’s risks against its promise as a lifesaving medication.

In four studies of knee and hip replacement patients, rivaroxaban cut the risk of blood clots or death in half, to 0.6 percent, compared with 1.3 percent for patients taking Lovenox.

Rivaroxaban is one of several new anticlotting drugs designed to be safer and more effective than older treatments. One mainstay of anticlotting treatment, Coumadin or warfarin, requires patients to undergo frequent blood tests because a too-high or too-low dose can lead to strokes or dangerous bleeding.

“If we look at our program, we believe we have a very effective drug with a very positive benefit risk profile,” J&J; Vice President Peter Wildgoose said in an interview last week.

J&J; is studying the drug in more than 60,000 patients for additional uses, including stroke prevention and treatment of coronary artery disease.

If the drug is approved, Johnson & Johnson’s Ortho-McNeil business will sell the drug in U.S., while Bayer HealthCare AG will have marketing rights in other countries.

Shares of New Brunswick, N.J.-based J&J; fell $1.18, or 2.3 percent, to $49.56 in morning trading.

Copyright 2009 The Associated Press.

FDA holds safety hearing on 50-year-old painkiller

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Posted on 30th January 2009 by Gordon Johnson in Uncategorized

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Date: 1/30/2009

By RICARDO ALONSO-ZALDIVAR
Associated Press Writer

WASHINGTON (AP) — Call it the cold case file of drug safety.

Federal health officials convened a public hearing Friday on whether to ban Darvon, a painkiller first approved in 1957, when there were few alternatives for treating pain except aspirin and powerful narcotics.

Now mainly marketed as Darvocet, which includes a dose of acetaminophen, the drug remains one of the top 25 most commonly prescribed medications. More than 20 million prescriptions were written in 2007.

The consumer group Public Citizen said the FDA should withdraw Darvon from the market because the drug offers relatively weak pain relief and poses an overdose risk, with the potential to be used in suicides.

“It has unique risks and no unique advantages,” said Dr. Sidney Wolfe, a drug safety expert with Public Citizen who first sought a ban in the 1970s. “It has been a big drug of abuse for quite a long time.”

Two companies that market the drug — Xanodyne Pharmaceuticals and Qualitest/Vintage Pharmaceuticals— say the medication is safe and effective when used as directed. In documents filed with the FDA, the companies say doctors need a range of options to treat pain, and note that many other painkillers have become drugs of abuse.

Dr. Jerry Avorn, a professor of medicine at Harvard and a critic of the pharmaceutical industry, is glad the FDA is taking a hard look at Darvon.

“I have been astonished at how widely used this drug is,” Avorn said. “It’s no longer the most abusable and most dangerous drug in its class, but the fact that there are worse drugs doesn’t make Darvon a good drug.”

The United Kingdom banned its version of Darvon in 2005. The FDA, however, may take a more cautious approach, such as requiring stiffer warnings, safety studies or special education efforts aimed at doctors and patients.

The FDA awaited recommendations Friday from a panel of independent advisers.

In an analysis prepared for the hearing, the FDA’s safety office said it had searched the agency’s database of reported drug problems, but the result was “insufficient” to allow reviewers to make a clear-cut recommendation. The safety office found more than 3,000 reports of serious problems. The top three were suicide, drug dependence and overdoses.

In a separate analysis, the FDA office that handles painkillers said Darvon is a weak pain reliever. Most studies show that in Darvocet, the widely used combination drug, the Darvon component appears to contribute “little or no” additional pain relief beyond that provided by the acetaminophen component, reviewers said.

Wolfe presented the advisory panel with new data from the government’s Drug Abuse Warning Network, which tracks emergency room visits and deaths. It showed that Darvon-related deaths rose to 503 in 2007, from 446 in 2006. In both years, about 20 percent were suicides. The network covers only about one-third of the U.S. population.

Data from the Florida’s medical examiner reporting system showed that in 2007 Darvon was present in the bodies of 341 people who died from drug-related causes. Medical examiners identified it as the cause of death in 85 of the cases, or 25 percent.

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On the Net:

FDA meeting agenda: http://tinyurl.com/cg5k5a

Copyright 2009 The Associated Press.

Safety a problem for new generation drugs, too

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Posted on 21st October 2008 by Gordon Johnson in Uncategorized

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Date: 10/21/2008 10:00 AM

By LINDSEY TANNER
AP Medical Writer

CHICAGO (AP) _ Nearly a fourth of widely used new-generation biological drugs that treat several common diseases produce serious side effects that lead to safety warnings soon after they go on the market, the first major study of its kind found.

Included in the report released Tuesday were the arthritis drugs Humira and Remicade, cancer drugs Rituxan and Erbitux, and the heart failure drug Natrecor. All wound up being flagged for safety.

That might surprise some doctors who may have thought that these new treatments might be safer than traditional chemical-based medicines.

Researchers found that most of the warnings came within five years after these biologicals won government approval in the United States and Europe between 1995 and 2007.

Many traditional medicines wind up with safety warnings too after they go on the market. But experts said there were no similar studies of older medicines that made it possible to compare safety issues between the two groups of drugs.

The new study, by Dutch researchers, is the first comprehensive examination of these newer medicines, a driving part of the biotech revolution.

The new drugs are known as biologicals because they’re made from living material and often work by triggering the body’s disease-fighting immune response.

It’s that same mechanism that can result in side effects often not seen with traditional chemical-based medicines, including major infections and cancer, said Dr. Charles Bennett, a Northwestern University drug safety expert. He was not involved in the research.

Many are genetically engineered and Bennett said that because they typically resemble naturally occurring proteins, many doctors have assumed they were safer than traditional chemical-based medicines. But he said the study shows that’s not necessarily true.

“They have an important role,” Bennett said. “They’re really the next generation of pharmaceuticals.”

He said the results simply show that doctors and patients should be aware that the drugs have many potential side effects that may not be listed on the label.

Among the drugs under examination are Genentech Inc.’s psoriasis drug Raptiva, which just last week the Food and Drug Administration warned may contribute to a life-threatening brain illness and infections; and Exubera, an inhaled insulin product, linked with lung cancer risks. Exubera was approved by the FDA in 2006 but Pfizer Inc. stopped selling it last year.

The study appears in Wednesday’s Journal of the American Medical Association.

It involved 136 biologics approved in the United States and 105 in the European Union between January 1995 and June 2007. A total of 41, or nearly 24 percent, got safety warnings issued through June 2008.

The results are a concern, and they underscore the need for closer scrutiny of drugs after their approval, said lead author Thijs Giezen of the University of Utrecht.

But he said the study also is reassuring because most problems showed up relatively soon after the drugs became available, which minimized the potential for widespread harm.

“If most issues are discovered within the first few years, then the system is working,” Giezen said.

Bennett says it’s unreasonable to think that the studied drugs’ safety issues should have been discovered before they were marketed. That’s because drug approval is based on relatively small studies with patients who generally are healthier than those in the general population. It often takes real-world experience for side effects to appear, he said.

Many biological drugs have advantages over conventional medicine, but the study shows their risks need to also be considered, said Thomas Moore of the Institute for Safe Medication Practices.

For example, non-steroid arthritis medicines including ibuprofen can reduce pain by decreasing inflammation, but they can cause stomach bleeding.

Biologic rheumatoid arthritis medicines Remicade, Enbrel and Humira are designed to ease painful joints by keeping the body’s immune system from attacking itself, the underlying problem in the disease. But they are much more expensive and have been linked with higher risks for potentially fatal infections. Also, the FDA is investigating possible cancer risks.

“My message to patients is that these biological products often can treat very difficult to treat diseases but may have very substantial risks and that you need to take extra care to educate yourself as to what those risks might be,” Moore said.

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On the Net:

JAMA: http://jama.ama-assn.org

Copyright 2008 The Associated Press.