Major
Methotrexate × tacrolimus
Antimetabolites, folic acid analogues×Calcineurin inhibitor (immunosuppressant)
Mechanism
Dual immunosuppression plus additive nephrotoxicity. The combination is used in rheumatoid arthritis patients on methotrexate when tacrolimus is added (e.g., in ANCA vasculitis), requiring careful monitoring.
Symptoms
Stomatitis, diarrhoea, falling leukocyte, platelet, and erythrocyte counts. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
The combination is possible in rheumatic disease with careful monitoring. Check full blood count, creatinine, and liver enzymes every 2 weeks for the first 3 months, then monthly. Keep tacrolimus trough (C0) at the lower end of target range.