Coadministration has not been studied but is not recommended. Sotorasib is metabolised by CYP3A4. Bictegravir is equally metabolized by CYP3A4 and UGT1A1 and does not inhibit or induce CYP enzymes. Sotorasib is a moderate inducer of CYP3A4 and may decrease bictegravir concentrations. Coadministration of bictegravir/emtricitabine/tenofovir alafenamide with rifabutin (a moderate inducer) decreased bictegravir Cmax, AUC and Cmin by 20%, 38% and 56%, respectively. Coadministration with moderate inducers Is not recommended in the product labels for Biktarvy. No interaction is expected with emtricitabine. Tenofovir alafenamide is a substrate of P-gp and inhibitors of P-gp such as sotorasib are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied. Clarithromycin is a strong inhibitor of CYP3A4 and P-gp and is predicted to increase bictegravir concentrations but to a modest extent. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC. However, tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and inhibitors of P-gp such as clarithromycin are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ivabradine’s metabolic pathway.