Atorvastatin × Warfarin

The US warfarin label (FDA) lists atorvastatin among inhibitors of CYP3A4, the enzyme that clears the R-enantiomer of warfarin, so in theory it could increase the warfarin effect. In practice, in a clinical study in patients on long-term warfarin, atorvastatin 80 mg a day slightly shortened prothrombin time, by about 1.7 seconds over the first 4 days, and it returned to normal by day 15. Clinically significant interactions have been reported only very rarely (atorvastatin SmPC). The US atorvastatin label also describes no clinically significant effect on prothrombin time.

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Measure prothrombin time (INR) before starting atorvastatin and often enough early in treatment to make sure there is no significant change; after that, monitoring follows the usual warfarin schedule. Repeat this if the atorvastatin dose is changed or the drug is stopped (atorvastatin SmPC). The FDA also advises close INR monitoring when a CYP3A4 inhibitor is started, stopped or changed in dose (US warfarin label).