Major
ritonavir × Warfarin
HIV protease inhibitor / pharmacokinetic booster×Vitamin K antagonist anticoagulants
Mechanism
Complex mechanism. Ritonavir inhibits CYP3A4 but simultaneously induces CYP1A2, CYP2C9, and CYP2C19 (long-term effect). The net effect on warfarin varies: in some patients INR rises, in others it falls.
Symptoms
If INR rises: gum bleeding, epistaxis, bruising without trauma, blood in urine or stool. If INR drops: thromboembolic risk (deep vein thrombosis, stroke in atrial fibrillation).
Management
When ritonavir starts, is escalated, or is withdrawn, check INR at 1, 2, and 4 weeks and titrate warfarin to effect. Alternative anticoagulant in HIV-positive patients: low molecular weight heparin for short courses (no CYP interactions).
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.