Critical
Apixaban × Ketoconazole
Direct oral anticoagulants (factor Xa inhibitors)×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole strongly inhibits both CYP3A4 and P-glycoprotein – the clearance routes of apixaban. Apixaban plasma levels roughly double. 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. Alternative antifungals: terbinafine or echinocandins. During ketoconazole therapy, replace apixaban with a parenteral anticoagulant.