Apixaban is metabolized mainly by CYP3A4/5 (with minor contributions from CYPs 1A2, 2C8, 2C9, 2C19, and 2J2) and is a substrate of P-gp and BCRP. Concentrations of apixaban may increase due to inhibition of P-gp and BCRP by glecaprevir/pibrentasvir. However, a large, retrospective, multi-centre cohort study of patients coadministered HCV DAAs and DOACs, including glecaprevir/pibrentasvir and apixaban, reported a low incidence of bleeding which was similar to historic controls of patients with liver disease on DOACs alone, providing reassurance that any increase in apixaban levels is unlikely to be clinically relevant. Patients should be reminded to promptly report any signs of bleeding or bruising as with anyone who is prescribed DOACs. [Note: Product labels state that apixaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. It is not recommended in severe hepatic impairment and should be used with caution in patients with mild or moderate hepatic impairment.]

Coadministration of glecaprevir/pibrentasvir and omeprazole (20 mg once daily) decreased glecaprevir Cmax and AUC by 22% and 29%. Coadministration of glecaprevir/pibrentasvir and omeprazole (40 mg once daily taken 1 hour before breakfast) decreased glecaprevir Cmax and AUC by 64% and 51%. When omeprazole was administered in the evening without food, glecaprevir Cmax and AUC decreased by 46% and 49%. Despite the decrease in glecaprevir exposure with omeprazole there is no change in pibrentasvir exposure and, therefore, virological suppression is expected to be maintained. The European SPC for glecaprevir/pibrentasvir indicates that no dose adjustment is required and the US Prescribing Information indicates no clinically significant interaction and no dose adjustment required. However, it is important to note that currently there are no data with doses of omeprazole greater than 40 mg once daily.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as folic acid undergoes deconjugation and reduction

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is metabolised by multiple pathways (UGT1A1, GSH conjugation, CYP2E1, CYP1A2), none of which are expected to be affected by glecaprevir/pibrentasvir

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as thiamine is predominantly eliminated unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as acamprosate does not undergo significant metabolism.

Coadministration of glecaprevir/pibrentasvir (300/120 mg once daily) and buprenorphine/naloxone was studied in 12 subjects on individualized regimens of buprenorphine/naloxone. Dose normalized Cmax, AUC and C24 were slightly increased for buprenorphine (8%, 17% and 24%) and norbuprenorphine (25%, 30% and 21%). Naloxone dose-normalised Cmax and AUC were minimally affected (12% change or less). These changes were not considered clinically significant. Exposures of glecaprevir and pibrentasvir were similar to the observed values in previous studies. No dose adjustment is required.