FDA Slow to Sound Alarm on Pain Drug

Times Staff Writer

Dory Bauler prides herself on staying active despite painful back problems. But at one point this year, she was getting so short of breath that she could barely walk. Doctors could find nothing wrong.

It never occurred to them that the medicinal skin patch she was using to deliver pain relief might also be poisoning her.

“I was just shutting down,” said Bauler, 76, a retired paralegal from Laguna Woods in Orange County, who suffers from a severe curvature of the spine. “There were literally times I felt I wasn’t getting any oxygen at all.”


Bauler’s patch was delivering fentanyl, a narcotic many times more powerful than morphine. Like morphine and other opioid drugs, fentanyl controls pain but also reduces respiratory function -- and too much fentanyl can shut down one’s breathing entirely. Luckily, Bauler figured out what was happening in time to stop using the drug.

The leading brand of the fentanyl patch is Johnson & Johnson’s Duragesic; last year, pharmacists filled more than 4 million prescriptions for it.

The drug was developed to help people with extreme, unremitting pain, such as cancer patients. But it is increasingly being used for other medical conditions and, in some cases, by drug abusers.

Misuse can be lethal.

In the last six years, the Los Angeles County coroner’s office has investigated more than 230 deaths involving fentanyl. Of the deaths, records show 127 were classified as “accidental”-- suggesting that the victims inadvertently had taken too much. And evidence from other states and the Food and Drug Administration suggests there may be many more such cases nationwide.

The fentanyl patch illustrates a broad and still-unresolved problem with the nation’s system for protecting patients against drug risks: Neither the FDA nor the pharmaceutical industry has a comprehensive system for monitoring what happens after a new drug is approved for market.

Sometimes, as with the highly publicized discovery of heart and stroke risks associated with the painkiller Vioxx, the problem is that dangers show up only after millions of people begin using a drug. In other cases, as with fentanyl, the problem is that a drug approved for one purpose and in one context can be prescribed and used for other purposes. Known as off-label use, the risks of such use are not always understood.


“You’ve got a spectrum of the [drug safety] problem here,” said Dr. Alastair J.J. Wood, associate dean at Vanderbilt University Medical School and an advisor to the FDA. “There isn’t one easy solution. You need to have doctors think through whether this is the appropriate medicine for the patient.”

Cancer patients, for whom the fentanyl patch was developed, are usually monitored closely by a physician. Increasingly, however, the patches are being prescribed for other patients and conditions, sometimes without close monitoring.

The FDA says it is investigating about 130 fatalities that occurred over a 15-year period. Evidence from autopsies in Los Angeles and Florida suggests the number of fentanyl-related deaths may be much higher. The federal reporting system picks up a fraction of bad drug reactions.

“There are hundreds more cases not evaluated by the FDA,” said Bruce A. Goldberger, director of toxicology at the University of Florida Medical School.

In Los Angeles County, criminalist Daniel T. Anderson of the coroner’s office said the “vast majority” of fentanyl-related deaths involved the patch. The deaths occurred over a 5 1/2 -year period ending this summer.

For the 127 classified as accidental, it is believed that patients often misunderstood how to avoid the drug’s risks.


“Typically, the people we see here are people who have a legitimate use for the patch,” Anderson said. He had called attention to overdose deaths involving the Duragesic patch in a professional journal article published in 2000.

In Florida, state authorities reported 115 deaths from fentanyl poisoning in 2004, records show. Goldberger, whose office handles about one-fourth of the autopsies in the state, said the majority involved the patch.

Drug abuse involving fentanyl also is on the rise. Emergency-room cases involving the drug rose from 28 in 1994 to 1,506 last year, according to the federal Substance Abuse and Mental Health Services Administration.

“It is definitely a neglected drug safety problem,” Goldberger said.

As Congress weighs changes to strengthen the drug safety system, the history of the fentanyl patch shows that the FDA and many in the medical community knew of risks but failed to closely monitor the growing use of a potent narcotic.

Duragesic sales more than doubled from 2000 to 2004, as manufacturer Johnson & Johnson promoted it as safe in advertising to doctors that the FDA called “misleading.” With $1.2 billion in sales in 2004, Duragesic surpassed Vioxx, according to, a pharmaceutical website.

Yet as early as 2001, a drug safety group had warned that patients on the patch were dying of overdoses. Some doctors were prescribing the patch for patients who did not tolerate opioid drugs well, cautioned the Institute for Safe Medication Practices in Pennsylvania.


It took another four years for the FDA to issue its own nationwide alert, on July 15.

The FDA warnings, though welcome, are not enough, in the view of Michael Cohen, president of the safety group that initially sounded the alarm. Cohen, a pharmacist, said he was frustrated that the agency took so long to recognize the problem.

“We are the main safety organization for medication error reporting, and the FDA receives our information,” Cohen said. “Sometimes, information that is provided by us does seem to get lost within the FDA.”

Dr. Robert J. Meyer, head of the FDA office that oversees painkillers, said that safety officers this year noticed a trend of adverse reactions involving the drug.

“The system in place, though never ideal, does work well,” Meyer said. “The FDA did the right thing in [issuing] its communication. One of the things we need to think about in the future is continuing communications in terms of drugs like this that have some safety concerns.”

Cohen’s organization is calling for more aggressive FDA action, including a program to educate patients about the risks of the patch, new instructions for disposing of used and unwanted patches, and wider use of childproof packaging.

Vanderbilt’s Wood does not believe that warnings will suffice. “It’s like the warnings on an SUV: Beware of rollover,” he said. “The lawyers are happy with that, but does it prevent rollovers? Warnings probably don’t work.”


Bauler, the Laguna Woods paralegal, said reading a newspaper report about the FDA warning may have saved her life. She took herself off the patch, and her breathing problems cleared up in a few days.

“It was like having to be my own detective,” Bauler said. “Then I got angry. I have been through this hell that could have been prevented.”

Others were not so fortunate. Among the victims was a preschooler from East Toledo, Ohio. Four-year-old Timothy Rhodes was found dead in January after he got hold of a Duragesic patch prescribed for his mother, Stephanie, her family said.

A spokesman for Johnson & Johnson, which makes Duragesic, said the drug met an important need for cancer patients and others with chronic pain. The company is working with the FDA, doctors and patients to make sure it is used safely -- and has introduced child-resistant packaging, Doug Arbesfeld said.

“We take the health and safety of the patients who use this product very seriously,” Arbesfeld said. “We work very closely with the FDA to look into all reports of serious adverse consequences, and we believe that the product is safe and effective when used as directed.”

The manufacturer had promoted Duragesic to doctors as superior medication for back pain and other problems.


“Game, uninterrupted,” reads the caption on a Duragesic brochure that showed a middle-aged man shooting pool.

Another photo showed a pair of hands kneading dough. “1,360 loaves

Last year, the FDA sent the company a sharply worded letter about its advertising to doctors. The agency said many of the claims about Duragesic were not substantiated.

And, “by suggesting that Duragesic has a lower potential for abuse compared to other opioid products, the [promotional material] could encourage the unsafe use of the drug, potentially resulting in serious or life-threatening hypoventilation” -- a reduced capacity to breathe, the FDA said.

Arbesfeld said the company had stopped using the literature.

The FDA approved Duragesic in 1990 to treat chronic pain. The patch consists of a drug reservoir encased in a soft plastic film. When applied to the body, it releases fentanyl through a membrane. The drug is absorbed into the upper layers of the skin and circulates through the bloodstream.

From the beginning, Duragesic carried strong warnings. Doctors were cautioned about fentanyl’s potency. Patients were warned not to use more than one patch and to avoid seemingly innocuous actions that could cause the drug to be released more rapidly, such as wearing a heating pad or sunbathing.

Physicians and pharmacists say the patch is a good treatment for patients with severe pain. Each patch can be worn for 72 hours, maintaining a stable level of painkiller in the body.


“If you have a patient who can’t swallow pills, it is really important to have patches available,” said Dr. Judith Ford, a professor of radiation oncology at UCLA’s Jonsson Comprehensive Cancer Center. Ford says she starts her patients with a small dose and asks them to keep diaries to track the results.

“Fentanyl is a useful drug, but the market is not very big,” said Larry Sasich, a pharmacist who teaches drug policy at the Lake Erie College of Osteopathic Medicine in Erie, Pa. “This is a serious drug for serious pain, and that is a pretty limited market.”

But the fact that Duragesic comes in a patch may have made it seem more benign to patients than other strong painkillers.

Ford said she recalled a conversation with a patient who did not want to take another narcotic because he feared becoming addicted. But the same patient had no problems with using the patch, although fentanyl also can create dependency.

Roslyn Joress of Boynton Beach, Fla., said her doctor put her on the Duragesic patch for pain for a connective tissue disorder called fibromyalgia.

“I didn’t even realize that I was on a narcotic for the longest time,” said Joress, 67. “I thought it was like another medication they come out with in patch form and that it was going to relax the muscles. If the doctor had said to me, ‘This is like morphine,’ never in my wildest dreams would I have taken it.”


Joress said she found out Duragesic was a narcotic from another woman she saw wearing a patch at poolside.

When Joress tried to strike up a conversation about the patch, the woman responded, “Oh yeah, I’m a junkie.”

Joress got scared and decided to quit the drug, but went through intense withdrawal symptoms.

“I went from an addiction I didn’t even know was an addiction, to needing sleeping aids,” she said.

As for her pain, “it’s nothing a couple of Tylenol won’t take care of.”



Pain patch profits

From 2000 to 2004, sales of Duragesic, the leading brand-name painkiller patch, more than tripled, and the number of prescriptions more than doubled.


(in millions)

(In millions)

2000: $352.9

2001: $530.0

2002: $752.7

2003: $1,049.8

2004: $1,208.4



(In thousands)

2000: 1,766

2001: 2,426

2002: 3,009

2003: 3,659

2004: 4,114