Moderate
Atorvastatin × Methotrexate
HMG-CoA reductase inhibitors (statins)×Antimetabolites, folic acid analogues
Mechanism
Atorvastatin blocks OATP1B1 – the hepatic methotrexate uptake route. Methotrexate plasma levels may rise. The effect is clinically significant at high oncologic methotrexate doses.
Symptoms
Stomatitis, diarrhoea, falling leukocyte and platelet counts. In patients with borderline renal function: severe toxicity risk.
Management
At low rheumatological methotrexate doses (5–25 mg/week), the combination is acceptable without adjustment. At high oncologic doses, temporarily withhold atorvastatin for 24–48 hours after methotrexate administration.