Are there any known interactions between methotrexate and clindamycin?/nA patient with rheumatoid a

Fråga: Are there any known interactions between methotrexate and clindamycin?

A patient with rheumatoid arthritis treated with methotrexate needs an antibiotic. The physician does not want to use flucloxacillin because of risk of interaction with methotrexate. Can clindamycin be used concomitantly with methotrexate?

Sammanfattning: Since clearance of methotrexate is mainly dependent on kidney function, and clearance of clindamycin is mainly dependent on liver function, there is no theoretical basis for a metabolic interaction. There are no published reports of an interaction between methotrexate and clindamycin. Thus it appears to be safe to combine these dugs. However, when used to treat non-malignant conditions, a temporary withdrawal of methotrexate should be considered during an infection, since it acts as an immunosuppressant.

Svar: Methotrexate is an antifolate used in treatment of neoplasias and non-malignant conditions such as rheumatoid arthritis and psoriasis. Of the drug absorbed, about 90% is excreted unchanged in the urine. A small amount of methotrexate is also excreted in the stool, probably through the biliary tract. Metabolism of methotrexate is usually minimal, but after high doses metabolites do accumulate. One of the metabolites, 7-OH-methotrexate, is potentially nephrotoxic. Renal elimination of methotrexate occurs via glomerular filtration and active tubular secretion. Concurrent use of drugs that reduce renal blood flow, that are nephrotoxic or that are weak organic acids can result in delayed excretion. In patients with renal insuffiency, dose adjustments must be made (1).

Clindamycin is a derivate of lincomycin. Clindamycin binds exclusively to the 50 S subunit of bacterial ribosomes and suppresses protein synthesis. Clindamycin is inactivated by metabolism to N-demethyl-clindamycin and clindamycin sulfoxide, wich are excreted in the urine and bile. Accumulation of clindamycin can occur in patients with severely impaired liver function, dose adjustments may be required. Only 10% of clindamycin is excreted unaltered in the urine and small amounts are found in the feces (1).

Since clearance of methotrexate is mainly dependent on kidney function, and clearance of clindamycin is mainly dependent on liver function, there is no theoretical basis for a metabolic interaction.

A search of the literature has not revealed any reports of interactions between methotrexate and clindamycin. It therefore appears to be safe to combine these drugs. However, when used to treat non-malignant conditions, a temporary withdrawal of methotrexate should be considered during an infection (2), since it acts as an immunosuppressant. 1 Hardman JG, Limibrd LE, Goodman Gilman A, editors. Goodman & Gilman´s The pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill; 2001 2 FASS 2002 (The Swedish catalogue of approved medical products)