Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. Furthermore, coadministration of bictegravir with medicinal products that potently inhibit both CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of bictegravir, therefore coadministration is not recommended. Coadministration of bictegravir (75 mg) and atazanavir alone (400 mg once daily) increased bictegravir AUC by 315%.

Coadministration is contraindicated in the European SPC (but no longer in the US Prescribing Information) for efavirenz as St John's wort is expected to substantially decrease efavirenz concentrations and may result in sub-optimal levels. If a patient is already taking St John's wort, stop St John's wort, check viral levels and if possible efavirenz levels. Efavirenz levels may increase on stopping St John's wort and the dose of efavirenz may need adjusting. The inducing effect of St John's wort may persist for at least 2 weeks after cessation of treatment. However, a recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp). Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of 1 mg or less.

Coadministration has not been studied and is contraindicated in the product labels for Biktarvy as St John’s wort may substantially decrease bictegravir and tenofovir alafenamide plasma concentrations which may result in loss of therapeutic effect and development of resistance. However, a recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp). Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of 1 mg or less. No interaction is expected with emtricitabine.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, efavirenz is an inducer of CYP3A4 and is expected to decrease bictegravir exposure which may result in loss of therapeutic effect and development of resistance. 

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. Furthermore, Biktarvy contains tenofovir alafenamide and should not be administered with tenofovir-DF. Biktarvy should not be administered concomitantly with medicinal products containing tenofovir used for the treatment of HBV infection.

Coadministration is contraindicated in the product labels for atazanavir as St John’s wort is expected to substantially decrease atazanavir concentrations, leading to loss of therapeutic effect and possible development of resistance. However, a recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp). Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of 1 mg or less.

Coadministration with atazanavir alone is not recommended. Coadministration of tenofovir-DF (300 mg) and atazanavir (400 mg) decreased atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively, but increased tenofovir AUC, Cmax and Cmin by 24%, 14% and 22%, respectively. If coadministration is necessary, patients should be closely monitored for tenofovir-associated adverse events, including renal disorders.

Coadministration with atazanavir alone is not recommended as efavirenz decreases atazanavir exposure. Coadministration of atazanavir (400 mg once daily) and efavirenz (600 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 74%, 59% and 93%, respectively. Furthermore, a prolongation of the QT interval may occur with efavirenz treatment in carriers of CYP2B6*6/*6. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. Efavirenz has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration decreases dolutegravir exposure and a dose increase of dolutegravir is recommended. Coadministration of efavirenz (600 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 39%, 57% and 75%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of efavirenz. In treatment-naïve or INSTI-naïve patients, a dose adjustment of dolutegravir to 50 mg twice daily is recommended. Alternative combinations that do not include metabolic inducers should be considered where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks  in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

Coadministration has not been studied. No effect is expected on bictegravir as curcumin and/or turmeric extracts had no significant effect on the pharmacokinetics of probe drugs for various UGT enzymes. Although curcumin inhibits BCRP, a clinically relevant effect on bictegravir is unlikely. No effect is expected on emtricitabine, however, the effect on tenofovir alafenamide is unclear as curcumin and/or turmeric extracts appeared to inhibit P-gp in vivo, but a contradictory effect was observed in vivo. No a priori dose adjustment is recommended.

Coadministration has not been studied. The effect on tenofovir-DF is unclear as curcumin and/or turmeric extracts appeared to inhibit P-gp in vivo, but a contradictory effect was observed in vivo. No a priori dose adjustment is recommended.

Coadministration of atazanavir (400 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 50% and 91%, with Ctrough increasing by 2.8-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. No dosage adjustment is necessary. The European SmPC for dolutegravir advises that dolutegravir should not be dosed higher than 50 mg twice daily in combination with atazanavir due to lack of data.

Coadministration of tenofovir-DF (300 mg once daily) and efavirenz (600 mg once daily) had no effect on the Cmax, AUC or Cmin of either tenofovir or efavirenz.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Data from pharmacokinetic studies suggest that turmeric and curcuminoids (derived from turmeric extract) are unlikely to affect CYP3A4-mediated metabolism.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Data from pharmacokinetic studies suggest that turmeric and curcuminoids (derived from turmeric extract) are unlikely to affect CYP3A4-mediated metabolism.

Coadministration has not been studied. St John’s Wort, an inducer of P-gp, could reduce the absorption of tenofovir-DF. However, based on the results of the interaction study between tenofovir-DF and rifampicin (another inducer of P-gp), St John’s Wort would be expected to cause only a small decrease in tenofovir-DF.  

No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. No dosage adjustment is necessary.