Apixaban × Ritonavir

Ritonavir strongly inhibits CYP3A4 and P-glycoprotein, which is why it is used as a pharmacokinetic booster in HIV regimens. Apixaban is cleared through both routes. According to the apixaban SmPC, strong CYP3A4 and P-gp inhibitors may double apixaban exposure, or raise it further in severe renal impairment. No label lists the pair as a contraindication: the EMA advises against it, and the FDA asks for a dose cut or avoidance.

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage, gross haematuria with renal colic, spontaneous retroperitoneal haematomas. Symptoms may appear within days of co-prescription.

The combination is not recommended. If a person with HIV on ritonavir needs anticoagulation, a drug without this interaction is chosen: a low-molecular-weight heparin for short courses, or warfarin. With warfarin, the FDA ritonavir label recommends frequent INR checks at the start of co-administration, because ritonavir can shift warfarin levels either way. The FDA also allows apixaban: a dose of 5 or 10 mg twice daily is halved, and at 2.5 mg twice daily the combination is avoided. The patient is told the signs of bleeding: black stools, blood in the urine, bruising without injury.