Ampicillin and rifampicin markedly reduce colonic release of5-aminosalicylate (the active drug) from sulfasalazine
In a study in 5 healthy subjects conversion and release of active metabolite of sulfasalazine, 5-aminosalicylic acid was reduced by one third when a single 2-g dose of sulfasalazine was given after a 5-day course of ampicillin 250mg four times daily (See reference number 1).
A crossover trial in 11 patients with Crohn’s disease receiving long-term treatment with sulfasalazine found that rifampicin 10 mg/kg daily and ethambutol 15 mg/kg daily reduced plasma levels of both 5-aminosalicylic acid and sulphapyridine by about 60 % (See reference number 3). A similar study in patients taking sulfasalazine 1.5 g to 4 g daily found that plasma sulfapyridine levels were reduced by 57 % when patients were taking rifampicin 10 mg/kg and ethambutol 15 mg/kg daily, when compared with placebo. They also noted an increase in erythrocyte sedimentation rate (ESR) during antibacterial treatment (See reference number 4).
The azo link of sulfasalazine is split by anaerobic bacteria in colon to release sulphapyridine and 5-aminosalicylic acid, latter being active metabolite that acts locally in treatment of inflammatory bowel disease. Antibacterials that decimate gut flora can apparently reduce this conversion and this is reflected in lower plasma levels. Rifampicin also possibly increases metabolism of sulphapyridine.
Information is limited, but interaction appears to be established. However, extent to which these antibacterials actually reduce effectiveness of sulfasalazine in treatment of Crohn’s disease or ulcerative colitis seems not to have been assessed, but be alert for evidence of a reduced effect if ampicillin, rifampicin or any other oral antibacterial is given. Neomycin, which also affects activity of gut microflora, has been seen to interact similarly in animal studies,(See reference number 5) but limited evidence suggests metronidazole does not interact.
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