Risperdal and Prozac are among top five subjects of adverse event reports to FDA in 1995.

JANSSEN RISPERDAL ACCOUNTS FOR 2% OF POST-MARKETING ADE REPORTS to FDA, according to the agency's 1995 Annual Adverse Drug Experience Report released in late January by the Division of Pharmacovigilance and Epidemiology. The agency received 2,540 adverse event reports for Risperdal (risperidone) out of a total of 130,950 ADEs reported during 1995, making the antipsychotic the fifth most frequently mentioned "suspect" drug in the database.

Janssen said that the number of adverse experience reports in 1996 for Risperdal "declined nearly 30% from 1995, even though usage of the product increased nearly 50% during the same period". The company maintained that the number of ADEs reported for Risperdal in 1995 "is not unexpected" and that "there is a naturally higher rate of adverse event reports for serious disorders such as schizophrenia, especially for newly approved drugs."

Lilly's Prozac (fluoxetine) was third on the FDA ADE list for 1995. There were 3,253 ADE reports for the antidepressant. The drug is the third highest selling brand in the U.S., and has been the subject of widespread publicity about its potential benefits and side effects.

Wyeth-Ayerst's Norplant (levonorgestrel implants) ranked second with 4% (5,712) of the reports. The contraceptive implant system has been the subject of numerous product liability suits, and the publicity surrounding those cases has presumably increased ADE reporting. The Population Research Institute seized upon the high incidence of ADEs relative to other drugs in the report to renew its argument that Norplant should be withdrawn from the market. The population group filed a petition with FDA in June 1996 calling for the removal of Norplant in light of patient complaints and side effects.

Another contraceptive agent, Pharmacia & Upjohn's Depo-Provera (medroxyprogesterone acetate), represented 2% (2,647)of the ADE reports. Direct-to-comsumer ads for Depo-Provera include a toll free number that encourages patients to report adverse events, the company said. Merck's Mevacor (lovastatin) ranked ninth and Abbott's Biaxin (clarithromycin) tenth, each with 1% of the reports. Up to 2 mil. patients receive Mevacor at a given time, Merck said, with headaches and gastrointestinal disorders being the most common side effects.

Procter & Gamble/Roche's OTC nonsteroidal anti-inflammatory drug Aleve (naproxen sodium) ranked first in ADEs with 5% (6,642) of the reports. Pharmacia & Upjohn's Rogaine (minoxidil), which was prescription in 1995 but went OTC in 1996, was ranked seventh with 2% (2,244) of the reports. Lilly's Humulin (insulin) accounted for another 2% (1,988) of the reports. The Today sponge, which was removed from the market in January 1995, also represented 2% (2,319) of the reports.

Central nervous system drugs were the class most commonly represented in reports to FDA with 28% (42,254 reports) of the 153,842 drug names cited in the reports. "Trend data from 1993 to 1995 show that only one drug class in the top five-ranked drug classes was common to both consumers and health professionals as well as all report types for all years: central nervous system," the report states.

Hormones and synthetic substitute ranked second with 14% (21,173) of the reports. Cardio-vascular drugs accounted for 10% (15,711) of the reports, and anti-infectives followed with 9% (10,191). Antineoplastic agents (7%), skin and mucous membrane agents (6%), autonomic drugs (4%), gastrointestinal drugs (4%) and blood formation and coagulation drugs (2%) rounded out the list of classes of suspect drugs reported. Unclassified drugs represented 4% of the reports.

Hospitalization, with 16% of the reports, was recorded as the most frequent serious outcome in the types of serious reports received by the agency. Death was the second most common serious outcome, with 5% of the reports. Outcomes considered to be life-threatening represented 4% of the reports. Disability and overdose both represented 2% and cancer represented 1%. Congenital anomaly represented less than 1% of the reports.

Of the ADEs submitted, 12% of the reports were made directly to FDA; the other 88% were reported by manufacturers through periodic reports (73%) or 15-day reports (16%). "Over a three-year trend (1993-5), reports from consumers have increased both in absolute numbers and proportionally, whereas those from health professionals have done the opposite," the report says.