Coadministration has not been studied but is contraindicated with strong cytochrome P450 3A4 inhibitors. Coadministration is likely to increase ivabradine concentrations which may be associated with the risk of excessive bradycardia.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with darunavir/cobicistat would be possible from a pharmacokinetic standpoint. Coadministration of bictegravir and darunavir/cobicistat increased bictegravir AUC 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, coadministration with darunavir/cobicistat (800/150 mg once daily) and tenofovir alafenamide (25 mg once daily) increased tenofovir AUC and Cmax by 224% and 216%, respectively. 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. Ayahuasca preparations contain N,N-dimethyltryptamine (DMT, a psychedelic substance along with monoamine oxidase inhibitors (MAOI) which attenuates the breakdown of DMT. MAOI are substrate of MRP2 which is inhibited by darunavir/cobicistat thereby potentially increasing DMT toxicity by slowing its breakdown. Given the narrow therapeutic index of DMT, caution is advised. Harma alkaloids found in ayahuasca preparations may cause weak/moderate inhibition of CYP3A4 which is unlikely to alter exposure of darunavir/cobicistat.

Coadministration has not been studied but may increase tadalafil concentrations and result in increased tadalafil-associated adverse events, including hypotension, visual changes, and priapism. For erectile dysfunction, use tadalafil with caution at a reduced dose not exceeding 10 mg in 72 hours with increased monitoring for adverse events.

Coadministration has not been studied. In vitro data showed that ketoconazole, a CYP450 inhibitor, can inhibit the metabolism of triclabendazole. As darunavir/cobicistat is an inhibitor of CYP450 enzymes, there is potential to increase levels of triclabendazole if coadministered, however the clinical significance of this interaction is unknown due to the short term dosing of triclabendazole.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Although in vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4, this is unlikely to impact the exposure of bictegravir as it is metabolized equally by CYP3A4 and UGT1A1. No effect on emtricitabine or tenofovir alafenamide is expected.

Coadministration has not been studied. In vitro, triclabendazole and its active sulfoxide metabolite are inhibitors of CYP3A4, and therefore may increase bictegravir exposure. However, due to short term dosing of triclabendazole (usually single dose), the clinical relevance of this interaction is low. Furthermore, renal excretion of unchanged triclabendazole appears to be minimal (<10%); therefore there is little potential for interaction with emtricitabine or tenofovir derived from tenofovir alafenamide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

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.