Moderate
Amiodarone × Methotrexate
Class III antiarrhythmics (Vaughan Williams)×Antimetabolites, folic acid analogues
Mechanism
No direct pharmacokinetic interaction. Cases of enhanced hepatotoxicity have been reported with long-term co-use, since both drugs can cause steatohepatitis and liver fibrosis.
Symptoms
Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms develop with long-term therapy (over 6 months).
Management
On the combination, check ALT, AST, and alkaline phosphatase every 3 months. If enzymes rise 2–3-fold above the upper limit, repeat at 2 weeks; if persistently elevated, consider temporary methotrexate withdrawal. In rheumatoid arthritis, alternative: leflunomide (if no liver fibrosis).
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.