Pain-Relief Patch Is Investigated in Patient Deaths

Federal regulators are investigating about 120 deaths that may be linked to overdoses from a pain-relief patch that administers a potent narcotic through the skin, the Food and Drug Administration said Friday.

Johnson & Johnson’s Duragesic patch can provide up to three days’ relief from severe chronic pain, such as that experienced by bone-cancer patients. But fentanyl, its active ingredient, is dangerous. An overdose of the morphine-like drug can put a patient into a coma and shut down breathing.

Fentanyl gained international notoriety in 2002 when Russian authorities trying to end a hostage crisis at a Moscow theater pumped in a gas reportedly containing the drug. They intended to put the hostages and their Chechen captors to sleep. Of the 750 hostages, about 120 died, nearly all from breathing the gas.

FDA officials said they were investigating whether the deaths among U.S. patients could be the result of unintentional fentanyl overdose. Such overdoses could come about if patients and doctors did not follow precautions contained in the prescribing literature, or label, for the drug.

Other possible explanations include rare problems or defects with the patches that would cause too much of the drug to be released into the body too quickly. And since many patients taking fentanyl are seriously ill, some of the deaths could also be the result of their diseases.

Doctors and patients should be aware of the signs of fentanyl overdose, which include trouble breathing or shallow breathing, tiredness, extreme sleepiness, inability to think, talk or walk normally, and feeling faint, dizzy or confused, the FDA said. Patients experiencing the symptoms should get medical attention immediately.

“The way people die is that it decreases the drive to breathe, so people will not breathe effectively,” said Dr. Robert Meyer, who heads the FDA office that regulates painkillers. “It [can] make patients very sedated or comatose.”

FDA officials said the agency announced the investigation in keeping with its new commitment to give the public earlier warnings of possible problems with prescription drugs.

The FDA has been criticized for taking too long to respond to evidence of heart attack risks with Vioxx and other arthritis drugs, and to evidence of suicide risks for teens taking antidepressants.

The fentanyl investigation is in its early stages, FDA officials said, and the agency has reached no decision on whether the patches should be recalled or their use limited. The agency issued a public health advisory Friday underscoring the need for patients to follow precautions.

“Some of the cases would seem to involve an overdose,” Meyer said. “We understand that labeling is not always understood or adhered to, and this is a way to reemphasize that these important warnings should be heeded.”

A spokesman for Johnson & Johnson said the New Jersey company had emphasized that Duragesic should be used with care.

“Patient safety is our first priority and it has been for the many years we have sold the drug,” spokesman Doug Stokke said. “We have consistently communicated to patients, caregivers and healthcare professionals information regarding the safe and appropriate use of Duragesic.”

Duragesic has been on the market since 1990, and the FDA said the 120 deaths reported to the agency spanned the entire period. Typically, the FDA’s reporting system picks up a fraction of serious drug reactions.

Mylan Laboratories Inc. began marketing a generic version of the drug this year.

Sales of brand-name Duragesic reached $1.2 billion in 2004, with more than 4 million prescriptions filled, said the website drugtopics.com. It ranked 24th in dollar sales among the top 200 drugs in 2004, and 93rd in the number of prescriptions.

Because of its risks, Duragesic and its generic equivalent carry a so-called black box warning, the FDA’s most emphatic.

On Friday, the agency underscored those warnings.

Doctors should prescribe the lowest effective dose of the medication, the agency said. And fentanyl patches should not be used to treat short-term pain or pain after an operation. Patients should not use patches that are damaged or broken. They also should not drink alcoholic beverages or sit in the sun while taking the drug, because alcohol and a rise in body temperature can accentuate the narcotic effects.

Stokke said Johnson & Johnson recently added to the warnings, notifying doctors that Duragesic should not be used by patients who could not tolerate opioid drugs.

People using the patches would include certain cancer patients, those who have difficulty swallowing pills and those who have problems injecting drugs.

“This is actually a useful drug,” said Dr. Peter Lurie, deputy director of health research for Public Citizen, an advocacy group often critical of the FDA. “But it’s also a particularly dangerous drug.”