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“Blood-Pressure Pill Okd
Before Study Ended”
by David Willman, published January 9, 2001 in Newsday and the Los Angeles
Times
Copyright, 2001, the Los Angeles Times. Reprinted with permission.
SENIOR FOOD AND DRUG Administration officials with the power to approve new
drugs were warned in advance about the dangers of Posicor, a pill for high blood
pressure and symptomatic chest pain.
The clinical studies of Posicor "cast a shadow of potential risk for serious arrhythmias," FDA medical team leader Dr. Shaw T. Chen wrote on Dec. 18, 1996. The data in hand also showed Posicor would interact with certain other drugs, posing potentially severe risk.
A 70-year-old man suffered "sudden death" in one study of Posicor's effect on chest pain. The senior FDA officials also were told of sudden deaths in 142 other patients who took either Posicor or a placebo in a study focused on congestive heart failure.
Details from the ongoing 2,400-patient study, however, remained sealed because the manufacturer opposed breaking the experiment's confidentiality regarding which patients were on Posicor and which were on the placebo until it was finished.
This left the FDA officials a choice: Wait a year or more, or approve Posicor without knowing the details.
"I sure don't feel good about what I've seen," said Dr. Lemuel A. Moye, a member of the FDA's Cardiovascular and Renal Drugs Advisory Committee that met Feb. 28, 1997. Moye suggested judgment be delayed until the study's results were unsealed and voiced concern about Posicor's effect on heart rhythm and its potential drug interactactions.
Another committee member, Dr. Robert Califf, said: "If this [drug] was really something that was dramatically different, better than anything else in the way of relieving symptoms, then I would look at it differently. But given the fact there are a lot of other effective therapies out there, why not be safe with the public?"
The drug's manufacturer, New Jersey-based Hoffman-La Roche Inc., saw no need to delay.
"There is no signal that there is arrhythmic or potentially arrhythmic risk with the drug," said Roche's Dr. Isaac Kobrin, terming the sudden deaths of four patients in another study "a chance finding." The committee voted 5-3 to recommend approval of Posicor, with Califf and Moye in the minority.
The committee chairman, Dr. Barry M. Massie of San Francisco, presided over the discussion but abstained from voting because he was a co-investigator in Roche's ongoing study of Posicor. After that meeting, Roche hired him as a speaker for the drug, Massie acknowledges.
On June 20, 1997, the FDA approved Posicor.
Four days later, a Roche news release quoted Massie to buttress the company's claim that "the incidence of side effects was low" during clinical studies of Posicor.
Doctors were cautioned in speck-sized type- beginning on the 278th line of the drug's label and again on the 365th-about prescribing Posicor in combination with various medications, including allergy pills, tranquilizers, a sleeping pill and the heartburn drug Propulsid.
Authorities in Sweden in mid-1997 saw sufficient danger to keep Posicor off the market.
Six months after approving Posicor, the FDA advised doctors of the pill's "life-threatening" danger. The agency announced it had "received reports of dangerously lowered heart rates in about 20 patients." Roche agreed to a label change-advising that Posicor should not be taken in combination with cholesterol-lowering drugs. This brought to 26 the number of drugs not to be prescribed with Posicor.
On June 8, 1998, Roche announced it was withdrawing Posicor, citing "evolving information concerning the potential for drug interactions" and "preliminary results" from the ongoing heart failure study that had drawn the attention of the advisory committee.
The study also found that the patients given Posicor died at a 10 percent greater rate than those who took another pill for high blood pressure.
Apart from the clinical research, records filed with the FDA show that doctors and others reported Posicor as a suspect in the deaths of 100 patients.
"Posicor should not have been approved," Moye said. "Therefore, any death that was attributable to Posicor was an unnecessary death."
