Does Methotrexate Reduce Other Drugs' Efficacy?
Methotrexate, a folate antagonist used for rheumatoid arthritis, cancer, and psoriasis, often decreases the efficacy of other drugs by competing for active transport or metabolic pathways. It inhibits dihydrofolate reductase, amplifying interactions that lower drug levels or activity.[1]
How Does Methotrexate Interact with NSAIDs?
Nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen compete with methotrexate for renal secretion via organic anion transporters, raising methotrexate levels and indirectly reducing NSAID anti-inflammatory effects through toxicity risks.[1][2]
Impact on Antibiotics and Antifungals
Methotrexate reduces trimethoprim efficacy in treating infections by both blocking folate synthesis. Penicillins and probenecid delay methotrexate clearance, potentially lowering antibiotic effectiveness in combination therapy.[1]
Effects on Antidiabetic Medications
It decreases metformin efficacy by competing for transporters, leading to lower metformin uptake and poorer glycemic control in diabetic patients on low-dose methotrexate.[2]
Interactions with Proton Pump Inhibitors
Omeprazole and other PPIs inhibit methotrexate renal excretion, elevating methotrexate exposure and risking reduced PPI acid suppression due to overlapping toxicity management needs.[1][2]
Cancer Drug Interactions
Methotrexate lowers 5-fluorouracil efficacy through thymidylate synthase competition. Conversely, it boosts some cytotoxics like cisplatin but reduces overall antitumor response in polychemotherapy by altering folate pools.[1]
Does Methotrexate Ever Increase Drug Efficacy?
Rarely; it enhances leflunomide immunosuppressive effects via shared antifolate mechanisms but primarily acts as an inhibitor, not enhancer, of most coadministered drugs.[2]
Sources
[1] Drugs.com - Methotrexate Interactions
[2] FDA Label - Methotrexate