Hoechst-Roussel Pharmaceuticals Inc., or its West German parent, delayed reporting at least 17 deaths among overseas users of an antidepressant called Merital to the Food and Drug Administration until after the FDA approved the medicine for the U.S. market, Rep. Ted Weiss (D-N.Y.) has charged.
The company waited six years to report the death of a woman in Italy, Weiss told FDA Commissioner Frank E. Young.
Although Hoechst AG, the parent company, knew of the death in 1980, Weiss said, the U.S. subsidiary did not notify FDA until last month, when it filed a report under a regulation requiring disclosure of alarming drug reactions within 15 days.
The report said the woman had developed hemolytic anemia, a rare disorder in which the immune system attacks and destroys red blood cells.
Dr. Robert J. Temple, the FDA's director of drug research and review, testified at a May hearing called by Weiss that hemolytic anemia first was reported as a side effect 3 1/2 months after the drug was approved by the FDA.
Pressed by Weiss, the FDA consented at the hearing to decide whether to seek criminal prosecution of Hoechst-Roussel for failing to make full, prompt reports of at least 58 cases of severe anemia in Merital users.
Weiss based his new charges on an investigation conducted by the subcommittee's staff.
He said Hoechst-Roussel's "failure to report to FDA a 1980 hemolytic anemia fatality associated with use of the drug represents additional grounds for questioning whether Merital was misbranded. . . . "
He asked Young to report on the status of the FDA's review of the company's compliance with regulations on reporting adverse reactions.
In Somerville, N.J., Hoechst-Roussel spokesman Donald R. Thorsen said the company had no immediate comment.
U.S. physicians prescribed the antidepressant for an estimated 190,000 persons after marketing began in July 1985. Six months later, Hoechst-Roussel withdrew the drug from the market, citing serious, and even fatal, reactions, "notably hemolytic anemia."
In letters that The Washington Post obtained from the agency under the Freedom of Information Act, Weiss told the FDA that Hoechst-Roussel had alerted FDA to none of several Merital-related fatal allergic reactions until several months after marketing approval.
"Many of these cases were strongly suggestive of allergic reactions to Merital," Weiss wrote.
"For example," he continued, "high fever -- a frequently observed manifestation of hypersensitivity to Merital -- was implicated in the death of a Merital patient in France that was reported to Hoechst in 1983." But, Weiss said, Temple's testimony that no overseas user had died of Merital-related fever as of Dec. 31, 1984, "may reflect the firm's failure to report this case prior to the drug's U.S. approval."
The Italian death was the subject of a memo that was written by a Hoechst AG official after conferring in February 1981 with a scientist of Hoechst's Italian affiliate. The memo "was circulated to at least two other Hoechst AG officials," Weiss told Young in the second letter, July 7.
According to the memo, the woman took Merital for seven months and then stopped. Several months later, she took one 25-milligram capsule and developed general malaise. For two days she did not take the drug. Then she took a second 25-mg. capsule and collapsed in shock with hemolytic anemia. "Then," the memo said, "the patient was treated in various departments of a large hospital, where, despite all therapeutic efforts, she died."
Actually, Weiss said, documents not cited in the June 1986 Hoechst-Roussel report to the FDA show that Hoechst AG and its affiliate in Italy knew of the case in 1980.
The report said a company report to the agency in January 1984 contained a table listing the Italian case as either an "unspecified reaction" or as an "ill-defined experience." But until last month, Weiss said in his letter, "no mention was made of the nature of the adverse experience or, for that matter, that it resulted in death."