Critical
ritonavir × Rivaroxaban
HIV protease inhibitor / pharmacokinetic booster×Direct oral anticoagulants (factor Xa inhibitors)
Mechanism
Ritonavir strongly inhibits CYP3A4 and P-glycoprotein – the clearance routes of rivaroxaban. Rivaroxaban plasma levels rise several-fold. The FDA lists the combination as an absolute contraindication.
Symptoms
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.
Management
The combination is not prescribed. For HIV patients, anticoagulate with warfarin under INR control or short-course low molecular weight heparin.