title: Spontaneous reports of thrombocytopenia in association with quinine: clinical attributes and timing related to regulatory action.
abstract: Quinine has been marketed in the United States (U.S.) both over-the-counter (OTC) and by prescription for numerous purposes, including malaria and muscle spasms. In 1994 and 1995, the U.S. Food and Drug Administration (FDA) acted to limit the marketing of quinine based on the conclusion that no data supported its safe and efficacious use in these settings. This report includes clinical attributes from the largest case series to date of apparently isolated thrombocytopenia in association with quinine and trends in the receipt of spontaneous adverse event reports to FDA's Center for Drug Evaluation and Research (CDER) for this drug-event combination in relation to regulatory action. In this study, we reviewed reports of spontaneous adverse drug events received by CDER. From 1974 through December 2000, CDER received 397 adverse event reports for quinine. Based on crude, unreviewed counts, 141 (35.5%) of these reports described apparently isolated thrombocytopenia. Reporting for this event peaked in 1995, coincident with regulatory action, and has subsequently declined. After elimination of cases confounded by acute or chronic disease or concomitant drug therapy, 64 reports of quinine-associated thrombocytopenia were used to form a case series. This case series, including 11 cases since January 1996, supports the potential for rapid time-to-onset (median 7 days) and clinical severity (hospitalization reported in 55 of the 64 cases). Although the number of reports since regulatory action is limited, CDER continues to receive reports of thrombocytopenia in association with quinine in use for nocturnal leg cramps. Extrapolation of spontaneous adverse event reports for a product with substantial OTC use precludes estimates of rates/incidence. Therefore, the effect of regulatory actions in 1994/1995 is difficult to measure using this approach. Although reports have decreased since regulatory actions on quinine, quinine remains available in the U.S. by prescription and in food products/dietary supplements. This case series confirms previous smaller series that suggest quinine-associated thrombocytopenia may present rapidly with symptoms of profound thrombocytopenia. Clinicians evaluating patients with new-onset and apparently idiopathic thrombocytopenia should maintain clinical vigilance for ingestion of quinine and elicit a detailed food/dietary supplement history from the patient.
authors.affiliation: Office of Drug Safety, Division of Drug Risk Evaluation, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA. brinkera@cder.fda.gov
authors.forename: Allen D
authors.initials: AD
authors.lastname: Brinker
authors.forename: Julie
authors.initials: J
authors.lastname: Beitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016208:Databases, Factual; D004335:Drug and Narcotic Control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011803:Quinine / Q000009:adverse effects*; D020922:Sleep-Wake Transition Disorders / Q000209:etiology; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology
chemical_list: D011803:Quinine