FDA Panel Backs Dopaminergic Impotence Drug – apomorphine
BETHESDA, MD. — A sublingual formulation of an old Parkinson’s drug was backed by a Food and Drug Administration panel for use in treating men with erectile dysfunction.
The FDA’s urology drugs advisory panel agreed 13-0 that studies of men with erectile dysfunction (ED) supported the indication. Most agreed that the data showed “an acceptable risk-benefit profile” for 2-mg and 4-mg doses of apomorphine, a centrally acting dopaminergic agent that is used for treating Parkinson’s disease.
In the hypothalamus, sublingual apomorphine increases the neural erectile signal to smooth muscle cells within about 30 minutes, said Dr. Jeremy Heaton, professor of urology at Queen’s University in Kingston, Ont. Currently available treatments for ED– sildenafil (Viagra) tablets and injectable prostaglandins–work peripherally to increase the intracellular signal in smooth muscle cells, he said.
If approved, this sublingual apomorphine will be marketed as Uprima by Tap Holdings, Waltham, Mass. The FDA usually follows the advice of its expert panels.
But apomorphine is not a benign drug. The panel recommended restrictive labeling and other efforts to warn of potentially serious side effects, such as syncope and hypotension. To reduce the risk of syncope, men using the drug should restrict alcohol intake or abstain from alcohol.
Tap reported on three crossover studies of heterosexual, largely white men, aged 21-76 years, with ED without a major organic component. The 4-mg dose led to an erection and successful intercourse in 54% of attempts, compared with 46% with 2 mg and 34% with placebo. That placebo response rate is typical of ED trials, one urologist on the panel noted.
The optimal dose appeared to be 4 mg, which was associated with more side effects. The most common adverse event was nausea in 20% of patients on 4 mg and 2% of those on 2 mg in the trials.
The FDA reported on cases of syncope and hypotension, including a 33-year-old who took 4 mg in a physician’s office, was observed for 30 minutes, and then drove home. After becoming nauseous, flushed, and sweaty, he lost consciousness and crashed. A 50-year-old who took 4 mg became nauseous and was found on the floor unconscious, apneic, diaphoretic, and unresponsive; he soon regained consciousness, but remained bradycardic and was admitted to the hospital.
Neither case was fatal, and none of the subjects who took apomorphine in clinical trials died or had a cardiac arrest, Tap reported. The overall incidence of hypotension and syncope was 0.7% among patients taking 2 mg or 4 mg. Dr. Mark Hirsh, an FDA medical officer, said syncope and hypotension usually occurred in the physician’s office and were “generally, but not always,” limited to the first dose or the first dose increase. The events occurred despite careful titration, he noted.
“This drug is clearly going to kill some people,” said a cardiologist on the panel, Dr. Robert Califf, professor of medicine at Duke University Medical Center in Durham, N.C. Still, he said that the 4-mg dose would meet his risk-benefit criteria, provided that the patient was not drinking alcohol, was not on “a slew” of cardiac medications, did not have three-vessel coronary artery disease, and did not drive a car for a few hours after taking the drug.
It’s unclear whether the drug is safe for men on nitrate therapy. Commenting on a Tap study of 40 patients on nitrates who took 5 mg of apomorphine or placebo, Dr. Marianne Mann, deputy director of the FDA’s division of reproductive and urologic drug products, said an interaction with nitrates was “possible.”
Viagra is contraindicated for use in men taking nitrates.
COPYRIGHT 2000 International Medical News Group
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