Major
Diclofenac × Methotrexate
Non-steroidal anti-inflammatory drugs (NSAIDs)×Antimetabolites, folic acid analogues
Mechanism
Diclofenac suppresses renal methotrexate excretion via prostaglandin-dependent blood flow inhibition and competition for tubular secretion. Methotrexate plasma levels rise – particularly dangerous at oncologic doses.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases include fatal pancytopenia, nephrotoxicity, and hepatotoxicity.
Management
At oncologic methotrexate doses, the combination is not prescribed. At low rheumatologic doses, short diclofenac courses are acceptable with full blood count and creatinine monitoring. For chronic analgesia: paracetamol or celecoxib.