Sulfasalazine Rifampicin

Antibiotics. Long-term administration of antibiotics could lead to vitamin B6 deficiency, If symptoms of peripheral neuropathy develop (numbness and tingling of the extremities), administer vitamin B6. Sulfasalazine can decrease the absorption of folic acid, and trimethoprim can cause folate deficiency, hence the need to administer folic acid if there is evidence of deficiency. Rifampicin can cause disturbances in vitamin D metabolism and lead to osteomalacia. The absorption of tetracyclines can be reduced by calcium, magnesium, iron and zinc, while this antibiotic could also decrease the absorption of these minerals. This effect is probably least with minocycline and is not confirmed with doxycycline. Doses of minerals and antibiotic should be separated by at least 2 hours. The absorption of quinolones is reduced by cationic and anionic supplements. 

Ampicillin and rifampicin markedly reduce the colonic release of 5-aminosalicylate (the active drug) from sulfasalazine. Metronidazole appears not to interact adversely with sulfasalazine. 

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 the plasma levels of both 5-aminosal-icylic acid and sulphapyridine by about 60%. A similar study in patients taking sulfasalazine 1.5 g to 4 g daily found that the 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 the erythrocyte sedimentation rate (ESR) during antibacterial treatment. ... 

The azo link of sulfasalazine is split by anaerobic bacteria in the colon to release sulphapyridine and 5-aminosaiicylic acid, the latter being the active metabolite that acts locally in the treatment of inflammatory bowel disease. Antibacterials that decimate the gut flora can apparently reduce this conversion and this is reflected in lower plasma levels. Rifampicin also possibly increases the metabolism of the sulphapyridine. 

Information is limited, but the interaction appears to be established. However, the extent to which these antibacterials actually reduce the effeetive-ness of sulfasalazine in the 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 the activity of the gut microflora, has been seen to interact similarly in animal studies, but limited evidence suggests metronidazole does not interact. 

---