Coadministration has not been studied. Doxazosin is metabolized mainly by CYP3A4 and coadministration may increase doxazosin exposure which can result in hypotension. For patients already taking darunavir/cobicistat, start doxazosin at the lowest dose (i.e., 1 mg daily) and increase dose slowly based on tolerance until an effective dose is reached. For patients already taking doxazosin, monitor blood pressure and reduce doxazosin dose as needed if hypotension occurs on starting darunavir/cobicistat.

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. Lisdexamfetamine is a prodrug of dexamfetamine and is not metabolized by CYP enzymes. Dexamfetamine is metabolized by CYP2D6 to some extent, whereas a large part is excreted unchanged. Darunavir/cobicistat is metabolized by CYP3A4. Lisdexamfetamine has no clinically meaningful effect on drugs metabolized by CYP3A4. Cobicistat is a weak inhibitor of CYP2D6 and could potentially increase dexamfetamine exposure (caution as non-linear pharmacokinetics). Monitor clinical effect and adjust dose if necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisdexamfetamine is a prodrug of dexamfetamine and is not metabolized by CYP enzymes. Dexamfetamine is metabolized by CYP2D6 to some extent, whereas a large part is excreted unchanged. Bictegravir is equally metabolized by CYP3A4 and UGT1A1 and does not inhibit or induce CYP enzymes. Lisdexamfetamine has no clinically meaningful effect on drugs metabolized by CYP3A4. No interaction is expected with emtricitabine or tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Darunavir/cobicistat is metabolized by CYP3A4 and does not affect CYP1A2. Caffeine is unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Bictegravir is equally metabolized by CYP3A4 and UGT1A1 and does not affect CYP1A2. Caffeine is unlikely to affect CYP3A4 or UGT1A1. No interaction is expected with emtricitabine and tenofovir alafenamide which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Darunavir/cobicistat is metabolized by CYP3A4. Creatine is unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Bictegravir is equally metabolized by CYP3A4 and UGT1A1. Creatine is unlikely to affect CYP3A4 or UGT1A1. No interaction is expected with emtricitabine and tenofovir alafenamide which are eliminated renally.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amyl nitrate is metabolized rapidly by hydrolytic denitration. Bictegravir, 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 pharmacokinetic interaction is unlikely. Amyl nitrate is metabolized rapidly by hydrolytic denitration.