Major
Methotrexate × naproxen
Antimetabolites, folic acid analogues×NSAID, propionic acid derivative
Mechanism
NSAIDs reduce renal methotrexate clearance via renal blood flow blockade and can displace methotrexate from plasma protein binding. Fatal cases have been reported at high oncologic methotrexate doses.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
At oncologic methotrexate doses, the combination is not prescribed. At low rheumatologic doses, a short naproxen course is acceptable with blood count and creatinine monitoring. For chronic analgesia: paracetamol or celecoxib.