Reported Adverse Drug Reaction Cases
Quinine and profound thrombocytopenia
ADRAC has published 2 previous Bulletin articles about quinine and thrombocytopenia but continues to receive reports of this serious problem.1,2 Since 1972, ADRAC has received 571 reports of suspected adverse reactions to quinine (sulfate or bisulfate), including 198 reports of thrombocytopenia, 4 of which had a fatal outcome. Twenty of these have been received since the beginning of the year 2000. The reactions generally occurred within 3 weeks of commencing quinine although two with intermittent use had a longer time to onset. In two cases the reaction occurred soon after the first dose. Seventeen of the 20 reports documented a platelet count which ranged between 0 and 14 x 109/L and most described hospitalisation and treatment with platelet transfusion, corticosteroids or immunoglobulin. Five reports described a positive quinine antibody test.
A recent illustrative report involved a 25 year old woman who had been taking quinine intermittently for nocturnal cramps. She had been taking about two tablets a week for 2 months. She presented with a generalised purpuric rash, and was found to have a platelet count of 5x109/L. Quinine was ceased, and she was hospitalised and treated with prednisolone and immunoglobulin. Her platelet count recovered to normal within a week. Drug-induced anti-platelet antibodies were detected.
Prescribers should consider the risks and likely benefits before prescribing quinine for nocturnal cramps, and should also consider other causes of cramp (for example, salt depletion particularly in summer, electrolyte disturbance, peripheral vascular disease, motor neurone disease). Meta-analyses have found that quinine prevents on average one or two cramps per week compared to placebo, without reducing the duration or severity of cramps.3 In 1995, the American FDA withdrew the indication of nocturnal cramps from all quinine products, because of a lack of evidence of efficacy, and the Australian Medicines Handbook recommends against its use for this indication.4 Daytime passive stretching of the calf muscles may be effective in preventing nocturnal cramps.
As illustrated in the case report above, thrombocytopenia usually recovers within a week of stopping quinine, but treatment with platelets, steroids or immunoglobulin may be required. Since quinine-induced thrombocytopenia occurs via an immune-based mechanism, patients should in future avoid all quinine-containing products, including drinks such as tonic water and bitter lemon.