Coadministration is not recommended. Oxacarbazepine is an inducer and is expected to decrease both tenofovir alafenamide and bictegravir exposures, which may result in loss of therapeutic effect and development of resistance. Alternative anticonvulsants should be considered.

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 assessed in pharmacokinetic studies. Oxcarbazepine is rapidly reduced by cytosolic arylketone reductases to its active metabolite, 10-hydroxycarbazepine. Oxcarbazepine is a moderate inducer of CYP3A4 and could potentially decrease cobicistat concentrations and consequently those of darunavir being boosted, leading to loss of therapeutic effect and possible development of resistance. Alternative anticonvulsants should be considered. If coadministration is necessary, monitor for lack or loss of virological response. Limited data from a small number of patients showed TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges and TDM results of darunavir were comparable with control values.

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Darunavir/cobicistat could potentially increase bisoprolol exposure, although to a limited extent. No a priori dosage adjustment is needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with bisoprolol’s metabolic pathway.