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.

Emtricitabine/tenofovir-DF (Truvada) is a fixed dose combination and should not be administered with additional emtricitabine.

Emtricitabine/tenofovir-DF should not be administered with additional tenofovir-DF. Coadministration of tenofovir-DF (300 mg once daily) and emtricitabine (200 mg once daily for 7 days) had no effect on tenofovir AUC, Cmax or Cmin; emtricitabine AUC and Cmax were unaltered and there was a 20% increase in Cmin (n=17).

Emtricitabine/tenofovir-DF should not be administered with additional emtricitabine or with tenofovir alafenamide.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products or with additional 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, both products contain emtricitabine and tenofovir alafenamide and must not be administered with other products containing emtricitabine and tenofovir alafenamide.

Coadministration has not been studied. Valaciclovir is converted to aciclovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1. Based on metabolism and clearance a clinically significant interaction between emtricitabine and valaciclovir is unlikely. Since tenofovir is primarily eliminated by the kidneys, coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir or the coadministered drug. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). No effect on chloroquine is expected. Concentrations of bictegravir may increase due to inhibition of P-glycoprotein by chloroquine but this is unlikely to be clinically significant as clinical data have shown a good safety profile with up to a 2.4-fold increase in bictegravir AUC. However, concentrations of tenofovir may also increase and 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. No effect on emtricitabine is expected.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. A clinically significant interaction due to competition for MATE1 is unlikely with emtricitabine as it has a wide safety margin. However, there is potential competition for OAT1 between cefalexin and tenofovir, which could lead to increased concentrations of either drug. 

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, the coadministration of rilpivirine would be possible from a pharmacokinetic standpoint.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated. Dolutegravir is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations.

Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 25% and 10% (n=10). No significant effects were observed on dolutegravir pharmacokinetics relative to historical controls. Coadministration of dolutegravir (50 mg once daily) and tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (10/200/150/150 mg) had no significant effect on the pharmacokinetics of dolutegravir and tenofovir alafenamide. The recommended dose of Descovy for HIV-1 treatment is 200/25 mg once daily.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leuprorelin acetate is a peptide that is primarily degraded by peptidases.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Bictegravir is unlikely to cause a clinically significant interaction via inhibition of MATE1. Emtricitabine and tenofovir alafenamide are unlikely to compete with cephalexin for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. This renal transporter does not play a major role in tenofovir and emtricitabine renal elimination. In addition, bictegravir is unlikely to interfere with cefazolin elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cefixime is renally excreted predominantly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clomipramine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with chlorphenamine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with chlorpromazine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clozapine’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated. Bictegravir does not inhibit or induce P450 and UGT 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. Valaciclovir is converted to aciclovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1. Bictegravir does not interfere with aciclovir elimination. Emtricitabine and tenofovir alafenamide are unlikely to compete with aciclovir for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolised 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. 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. Prazosin is extensively metabolized, primarily by demethylation and conjugation. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with prazosin’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolized mainly by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ecstasy’s metabolic pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clomifene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leuprorelin acetate is a peptide that is primarily degraded by peptidases.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. OAT3 does not play a major role in the renal elimination of emtricitabine and tenofovir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. As cefixime is renally excreted predominantly by glomerular filtration, with no significant active renal tubular secretion, there is little potential for an interaction with emtricitabine and tenofovir via competition for active renal elimination transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized via CYP2D6 and approximately 22% of a chlorphenamine dose is excreted unchanged in the urine. There is little potential for an interaction with emtricitabine and tenofovir via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also CYP1A2.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tadalafil is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin undergoes extensive hepatic metabolism primarily by demethylation and conjugation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolized mainly by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atorvastatin is metabolized by CYP3A4.

No clinically significant pharmacokinetic interaction was observed between rilpivirine and dolutegravir. Coadministration of rilpivirine (25 mg once daily) and dolutegravir (50 mg once daily) increased dolutegravir Cmax, AUC and Ctrough by 13%, 12% and 22%, respectively. Rilpivirine Cmax, AUC and Ctrough increased by 10%, 6% and 21%, respectively. No dosage adjustment is necessary. [Dolutegravir is available coformulated with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal excretion of clomifene is thought to account for approximately 8% of an oral dose. There is little potential for an interaction with emtricitabine and tenofovir via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leuprorelin acetate is a peptide that is primarily degraded by peptidases.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration of rilpivirine (150 mg once daily) and tenofovir-DF (300 mg once daily) decreased rilpivirine Cmax and Cmin by 4% and 1%, and increased AUC by 1%. Tenofovir Cmax, AUC and Cmin increased by 19%, 23% and 24%. No dose adjustment is necessary. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.]

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYP3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.