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. Prednisolone is metabolized by CYP3A4. Coadministration could potentially increase prednisolone concentrations thus increasing the risk of steroid related toxicity. Following administration of prednisone (20 mg single dose) to HIV+ subjects receiving either lopinavir/ritonavir or efavirenz or no antiretrovirals (n=10 per group), prednisolone AUC was significantly lower (40% decrease) in the presence of efavirenz versus lopinavir/ritonavir, and was higher in the subjects taking lopinavir/ritonavir than in subjects on no antiretrovirals (30% increase), but this was not significant. A similar increase may occur with darunavir/cobicistat. Careful monitoring for adverse effects is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clotrimazole undergoes hepatic metabolism (likely via CYP3A4) and is a moderate inhibitor of CYP3A4. Coadministration of clotrimazole as a pessary or troche is unlikely to cause a clinically significant increase in clotrimazole or darunavir/cobicistat exposure.

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 but based on metabolism and clearance a clinically significant interaction is unlikely as tranexamic acid is mainly cleared by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone undergoes hepatic metabolism. Bictegravir does not inhibit or induce P450 or UGT enzymes. Significant interactions are not expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tranexamic acid is mainly cleared by glomerular filtration.