Rifampicin induces metabolism of quinine, which may resultin subtherapeutic quinine levels.
Clinical evidence,mechanism, importance and management
A study in 9 healthy subjects found that clearance of a single 600mg dose of quinine sulfate was increased more than sixfold by pretreatment with rifampicin 600mg daily for 2 weeks
A report describes a patient with myotonia, controlled with quinine, whose symptoms worsened within 3 weeks of starting to take rifampicin for treatment of tuberculosis. Peak quinine levels were found to be low, but rose again when rifampicin was stopped. Control of myotonia was regained 6 weeks later (See reference number 2).
The effect of adding rifampicin to quinine was investigated in patients with uncomplicated falciparum malaria. They were taking quinine sulfate 10 mg/kg three times daily either alone (30 patients) or with rifampicin 15 mg/kg daily (29 patients) for 7 days. Peak plasma levels of quinine during monotherapy were attained within 2 days of treatment and remained within therapeutic range for 7-day treatment period. Levels of main metabolite of quinine, 3-hydroxyquinine, followed a similar pattern. In patients taking quinine with rifampicin, quinine was more extensively metabolised and, after second day of treatment, quinine levels were sharply reduced to below therapeutic levels. Acute malaria reduces metabolic clearance of quinine (by a reduction in hepatic mixed function oxidase activity, mainly by cytochrome P450 isoenzyme CYP3A4) and recovery is associated with a sharp decline in quinine levels. Rifampicin induces cytochrome P450 isoenzymes and this probably more than countered their inhibition during acute malaria and resulted in increased metabolism of quinine. Although patients who received rifampicin with quinine had shorter parasite clearance times than those who received quinine alone, suggesting rifampicin may enhance antimalarial activity of quinine, recrudescence rates were 5 times, higher suggesting increased resistance. [Note, recrudescence is reappearance of disease after a period of inactivity.] The authors suggest that rifampicin should not be given with quinine for treatment of malaria. Patients receiving rifampicin who also require quinine for malaria may need increased doses of quinine (See reference number 3).
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Pukrittayakamee S,Prakongpan S, Wanwimolruk S, Clemens R, Looareesuwan S, White NJ.Adverse effect of rifampin on quinine efficacy in uncomplicated falciparum malaria. Antimicrob Agents Chemother (2003) 47, 1509–13.