Methotrexate drug interactions

Andersen JB, Szumlanski C, Weinshilboum RM et al. Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta Paediatr 1998 87 108-111. 

Siegel, L.C. and T.K. Gandhi. Hospital Admission due to High-Dose Methotrexate Drug Interaction, AHRQ Web M M, January 2(X)9. 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and Gl toxicity have occurred with coadministration of methotrexate (usually in high dosage) along with some NSAIDs (see Precautions. Drug Interactions). 

No drug interaction studies have been conducted in humans. Animal studies indicate no change in the clearance or toxicity of either methotrexate or anakinra when the two agents are administered together. Concomitant administration of a TNF blocker appears to increase the risk of serious infection. The response to vaccines may be diminished in patients taking anakinra. 

Many drugs interact with folate to affect its absorption, antagonize its biochemical activity, or increase its loss from the body. These drugs include ethanol, phenytoin, and oral contraceptives. Salicylates can compete with foUc acid for plasma protein binding. Methotrexate, a cytotoxic agent, is a folate antagonist that inhibits the biosynthesis of this coenzyme. 

Drug interactions No formal drug interaction studies in human subjects have been conducted. Studies in rats did not demonstrate changes in the clearance of methotrexate or anakinra when the two drugs were administered together. 

Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamoda M, Cha SH, Sekine T, Endou H. Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther 2002 302 666-671. 

Breedveld P, Zelcer N, Pluim D, et al. Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res 2004 64 5804— 5811. 

Nozaki Y, Kusuhara H, Endou H, et al. Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier. J Pharmacol Exp Ther 2004 309 226-234. 

Furst DE. Practical clinical pharmacology and drug interactions of low-dose methotrexate therapy in rheumatoid arthritis. Br J Rheumatol 1995 34(suppl 2) 20-25. 

Drug Interactions Prolonged prothrombin times in patients receiving warfarin have been reported. Plasma half-life of pheny-toin (see p. 147) may be increased due to an inhibition of its metabolism. Methotrexate (see p. 378) levels may rise due to displacement from albumin binding sites by the sulfamethoxazole. 

Dupuis LL, Koren G, Shore A, Silverman ED, Laxter RM. Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis. J Rheumatol 1990 17 1469-73. 

Evans WE, Christensen ML. Drug interactions with methotrexate. J Rheumatol Suppl 1985 12(Suppl 12) 15-20. 

Frenia ML, Long KS. Methotrexate and nonsteroidal antiinflammatory drug interactions. Ann Pharmacother 1992 26 234-237. 

Drug interactions may potentiate methotrexate toxicity. For example nonsteroidal anti-inflammatory drugs can reduce renal clearance of methotrexate, resulting in toxic levels. Table 96-5 lists selected drugs that interact with, and increase toxicity of, methotrexate. 

Effective orally and eliminated via hepatic metabolism (acetylation) and renally as unchanged drug. Less water-soluble metabolites may cause crystalluria. Bind to plasma proteins —>T drug interactions including T effects of methotrexate, phenytofn, and warfarin. 

DRUG INTERACTIONS As do other NSAIDs, the propionic acid derivatives may interfere with the action of antihypertensive and diuretic agents, increase the risk of bleeding with warfarin, and increase the risk of bone marrow suppression with methotrexate. Ibuprofen also has been... 

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