Moderate
Simvastatin × Warfarin
HMG-CoA reductase inhibitors (statins)×Vitamin K antagonist anticoagulants
Mechanism
Simvastatin weakly inhibits CYP3A4 and partly displaces warfarin from protein binding. INR may rise by 0.5–1 in the first 2 weeks.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
On simvastatin initiation, check INR at 1 and 2 weeks, then per usual schedule. If INR rises, reduce warfarin by 10%. Alternatives: pravastatin or rosuvastatin (minimal warfarin effect).
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)– Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- Pharmaceutical Press: Stockley's Drug Interactions, 12th edition (2024)– Preston CL (ed.). Stockley's Drug Interactions. 12th ed. London: Pharmaceutical Press; 2024