The popular prescription nighttime heartburn drug Propulsid has been linked to 70 deaths and more than 270 significant negative reactions since 1993, the Food and Drug Administration warned yesterday.
The agency took the additional step of recommending that doctors test all patients before prescribing the drug to make sure they don't suffer from a heart condition or other ailments that would make taking the drug dangerous. It also said the drug, which can cause life-threatening irregular heartbeats, should only be used as a last resort.
"This is a serious problem, but in our view a rare problem," said Florence Houn, the FDA's chief for gastrointestinal drugs. "Doctors and patients need to understand and learn more about the risks and benefits of the drug."
The action by the FDA represents the latest attempt to warn doctors and the public about the possible dangers of Propulsid. The FDA has already strengthened Propulsid's label several times in recent years, with increasingly strong warnings to patients with certain heart rhythm disorders and those taking a wide range of other medications. When the agency significantly broadened the warning language in 1998, 38 deaths had already been associated with the drug.
But according to the FDA, 85 percent of the 270 adverse reactions occurred in patients with risk factors already outlined on Propulsid's label, people who were in clear danger of an adverse reaction to the drug.
A spokesman for Janssen Pharmaceutica of Titusville, N.J., an arm of Johnson & Johnson, said that while the new warning was warranted, the drug remained safe if used properly. The company yesterday sent a letter to doctors summarizing the new warnings and precautions on the drug's label.
About 6 million Propulsid prescriptions were sold last year and 30 million have been filled since the drug was approved, said Janssen spokesman Greg Panico. Propulsid was the 72nd-leading prescription drug in 1998, according to a survey by Scott-Levin Associates reported in the publication American Druggist.
"The fact that there have been only 270 adverse events after 30 million prescriptions points to the relatively rarity of the problem," Panico said.
Some consumer advocates have criticized the FDA in recent years for approving drugs before they have been thoroughly studied, and for approving drugs with known risks and failing to monitor them carefully enough once they are on the market.
Sidney M. Wolfe of the Health Research Group at Public Citizen, a frequent critic of FDA policies, said that Propulsid was a good example of what his consumer organization believes is going wrong at the agency.
"Most of the use of this drug is inexcusable," he said. "It was heavily promoted for acid reflux in the stomach when it came out, and that's when doctors got their impression about whether or not to use it. The FDA has made a series of warnings since then, but our studies show that doesn't really change prescribing patterns."
He said that Propulsid, or cisapride, should be taken off the market except for several specific research uses.
The FDA's Houn said the drug should not be pulled because it helps some patients who are not helped by other drugs. While doctors and patients need to know, and to discuss, the possible risks, they should have the right to use it, she said.
"Nighttime heartburn can be quite distressing, involving chest pains and difficulty breathing," Houn said. "Patients should first try avoiding certain foods and other lifestyle changes, and they should try the many other medications available. But for some people, nothing else will work."
In an effort to increase awareness of the drug's potential dangers, the FDA will hold a public advisory committee meeting April 12 to discuss its findings.
The new Propulsid label highlights known risks to patients taking a wide range of other medications, including antibiotics such as erythromycin, all protease inhibitors used for AIDS patients, and the class of anti-depressants including Elavil or Serzone. In previous warnings, the FDA had found it was dangerous to take Propulsid with grapefruit juice.
The FDA warning advises not only patients with irregular heartbeats and heart disease to avoid the drug, but also those with kidney disease, lung disease, eating disorders and low blood levels of potassium, calcium or magnesium.
Propulsid works by hastening the emptying of the stomach, and thereby reducing the painful reflux back into the esophagus.
Propulsid has been used in Europe since 1988, and company spokesman Panico said it is sold in 90 countries.
Johnson & Johnson shares closed yesterday at $83.68 3/4, down $6.18 3/4, or 6.9 percent.