title: How frequent are notified severe cutaneous adverse reactions to Fansidar?
abstract: An attempt was made to estimate the risk of severe cutaneous adverse reactions (SCARs) to Fansidar (sulfadoxine plus pyrimethamine). Cases were identified through a spontaneous reporting system. Persons exposed were estimated using sales data of 27 countries reporting one SCAR case for either Fansidar or a related product, Bactrim (cotrimoxazole; sulfamethoxazole plus trimethoprim). Between 1974 and 1989, 126 cases were notified for Fansidar: 87 cases of erythema multiforme or Stevens-Johnson syndrome, and 39 cases of toxic epidermic necrolysis. 86% of cases were reported in Europe or North America. In 116 cases with use known, prophylaxis was the reason in 103, and treatment in 13. Toxic epidermolysis and erythema multiforme/Stevens-Johnson syndrome had case fatalities of 36 (95% confidence intervals 21 to 53%) and 9% (4 to 18%), respectively. Fansidar users were estimated at 117 million, and the overall SCAR risk to be 1.1 (0.9 to 1.3) per million. For developing countries with mainly single dose use, the risk was estimated to 0.1 (0.0 to 0.1) per million. For Europe and North America with mainly prophylactic use, the risk was 10 (8 to 12) and 36 (23 to 48) per million, respectively. Prophylactic use had a 40 times higher risk than single dose therapeutic use. The aggregated risk peaked in 1984-1985, with global and North American SCAR frequencies of 3.4 (2.4 to 4.3) and 72 (41 to 102) per million, respectively. After 1985, North America reported only one further case despite continued use by an estimated 0.3 million persons.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Clinical Research and Drug Safety Departments, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Stürchler
authors.forename: M L
authors.initials: ML
authors.lastname: Mittelholzer
authors.forename: L
authors.initials: L
authors.lastname: Kerr
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D004338:Drug Combinations; D003875:Drug Eruptions / Q000453:epidemiology / Q000209:etiology*; D004363:Drug Utilization; D004892:Erythema Multiforme / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D011739:Pyrimethamine / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D013413:Sulfadoxine / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013413:Sulfadoxine; D011739:Pyrimethamine