Rifampicin increases metabolism of paracetamol. An isolatedreport describes hepatic failure,which may have been due to aninteraction between paracetamol and rifampicin.
Clinical evidence,mechanism, importance and management
The metabolite to paracetamol ratio for glucuronides was twice as high in 10 patients treated with rifampicin 600mg daily than in 14 healthy control subjects. In contrast ratio for sulfates did not differ between two groups.(See reference number 1)In a crossover study in healthy subjects, rifampicin 600mg daily for 1 week, given before paracetamol 500 mg, had no effect on formation of N-acetyl-p-benzoquinone imine (NAPQI) or recovery of thiol metabolites formed by conjugation of NAPQI with glutathione.(See reference number 2) These studies suggest that rifampicin induces glucuronidation of paracetamol, but that it does not increase formation of hepatotoxic metabolites of paracetamol, .
However,a 32-year-old woman, who had taken paracetamol 2 to 4 g daily for several weeks, and who had not responded to doxycycline or clarithromycin for suspected cat scratch fever, became confused and agitated 2 days after starting to take rifampicin 600mg twice daily. Her INR increased from 1.1 to 5.2 and her liver enzymes became raised. Rifampicin and paracetamol were stopped,and she was treated with vitamin K and acetylcysteine, and liver function returned to normal. Paracetamol hepatotoxicity, in doses not normally associated with such effects, occurred only after addition of rifampicin. It was suggested that rifampicin, which alone may cause hepatitis, had in this case induced metabolism of paracetamol to hepatotoxic metabolites (See reference number 3).
The clinical importance of studies awaits further study, but they suggest that rifampicin may reduce efficacy of paracetamol.
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