Coadministration of nevirapine (200 mg twice daily) with efavirenz (600 mg once daily) decreased efavirenz AUC (28%), Cmax (12%) and Cmin (32%), with no significant effect on nevirapine pharmacokinetics. Coadministration is not recommended because of additive toxicity and no benefit in terms of efficacy over either NNRTI alone.

Emtricitabine should not be taken with lamivudine due to potential competition for metabolism with other cytidine analogues.

Coadministration has not been studied and is not recommended as it may decrease rilpivirine concentrations. Combining two NNRTIs has not been shown to be beneficial. Furthermore, rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with efavirenz. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Efavirenz has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration is not recommended as it may decrease rilpivirine concentrations. Combining two NNRTIs has not been shown to be beneficial.

Genvoya (elvitegravir, cobicistat, 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. Furthermore, coadministering two integrase inhibitors (i.e., dolutegravir and elvitegravir) is unlikely to be of clinical benefit.

Genvoya (elvitegravir, cobicistat, 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. Furthermore, coadministering two integrase inhibitors (i.e., raltegravir and elvitegravir) is unlikely to be of clinical benefit.

Genvoya (elvitegravir, cobicistat, 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. Genvoya should not be used in conjunction with non-nucleoside reverse transcriptase inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir and/or the coadministered antiretroviral products. When switching patients who are CYP2B6 poor metabolisers from an efavirenz containing regimen to Genvoya, there is a potential for lower elvitegravir exposure due to prolonged CYP3A induction by efavirenz. Monitoring of viral load is recommended for these patients during the first month after switching treatment to Genvoya.

Genvoya (elvitegravir, cobicistat, 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. Genvoya should not be used in conjunction with non-nucleoside reverse transcriptase inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir and/or the coadministered antiretroviral products.

Genvoya (elvitegravir, cobicistat, 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. Furthermore, it must not be administered with additional emtricitabine.

Genvoya (elvitegravir, cobicistat, 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. Furthermore, Genvoya contains tenofovir alafenamide and should not be administered with tenofovir-DF. 

Genvoya (elvitegravir, cobicistat, 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. Genvoya should not be used in conjunction with protease inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir and/or the coadministered antiretroviral products. Genvoya should not be administered concurrently with products containing ritonavir or regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

Genvoya (elvitegravir, cobicistat, 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. Genvoya should not be used in conjunction with protease inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir and/or the coadministered antiretroviral products. Genvoya should not be administered concurrently with products containing ritonavir or regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

Genvoya (elvitegravir, cobicistat, 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. Furthermore, Genvoya contains emtricitabine and should not be administered with lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. 

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

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) and Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) are both indicated for use as complete regimens for the treatment of HIV-1 infection and must not be administered with other antiretroviral products. In addition, both products contain elvitegravir, cobicistat and emtricitabine and must not be administered with other products containing elvitegravir, cobicistat and emtricitabine. Furthermore, Genvoya contains tenofovir alafenamide and should not be administered with tenofovir-DF. 

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., raltegravir and elvitegravir) is unlikely to be of clinical benefit.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Stribild should not be used in conjunction with non-nucleoside reverse transcriptase inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the coadministered antiretroviral products.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Stribild should not be used in conjunction with non-nucleoside reverse transcriptase inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the coadministered antiretroviral products. When switching patients who are CYP2B6 poor metabolisers from an efavirenz containing regimen to Stribild, there is a potential for lower elvitegravir exposure due to prolonged CYP3A induction by efavirenz. Monitoring of viral load is recommended for these patients during the first month after switching treatment to Stribild.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, it must not be administered with additional emtricitabine.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Stribild contains emtricitabine and should not be administered with lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. 

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Stribild contains tenofovir-DF and should not be administered with additional tenofovir-DF. 

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Stribild should not be used in conjunction with protease inhibitors inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the coadministered antiretroviral products. Stribild should not be administered concurrently with products containing ritonavir or regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

Stribild is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Stribild should not be used in conjunction with protease inhibitors inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the coadministered antiretroviral products. Stribild should not be administered concurrently with products containing ritonavir or regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both products contain emtricitabine and tenofovir alafenamide and must not be administered with other products containing emtricitabine and tenofovir alafenamide. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and elvitegravir) is unlikely to be of clinical benefit.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing tenofovir-DF should not be coadministered with products containing tenofovir alafenamide. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and elvitegravir) 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. 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. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and raltegravir 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. In addition, nevirapine 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 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, Biktarvy contains emtricitabine and should not be administered with lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Biktarvy should not be administered concomitantly with medicinal products containing lamivudine used for the treatment of HBV infection.

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.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and coadministration with other antiretroviral agents is not recommended in the Genvoya product labels. Darunavir/cobicistat coformulations (Rezolsta; Prezcobix) contain cobicistat and should not be administered with other products containing cobicistat. Coadministration would be possible with unboosted darunavir (Prezista) in clinical situations requiring treatment intensification. 

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and coadministration with other antiretroviral agents is not recommended in the Stribild product labels. Darunavir/cobicistat coformulations (Rezolsta; Prezcobix) contain cobicistat and should not be administered with other products containing cobicistat. Coadministration would be possible with unboosted darunavir (Prezista) in clinical situations requiring treatment intensification. 

Coadministration has not been studied and is not recommended because it is expected to decrease darunavir/cobicistat exposure which may result in loss of therapeutic effect and development of resistance to darunavir. 

Coadministration has not been studied and is not recommended because it is expected to decrease darunavir/cobicistat exposure which may result in loss of therapeutic effect and development of resistance to darunavir. 

Darunavir/cobicistat coformulations (Rezolsta; Prezcobix) should not be administered concurrently with lopinavir co-formulated with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A4.

Darunavir/cobicistat coformulations (Rezolsta; Prezcobix) should not be administered concurrently with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A4.

Dovato (dolutegravir, lamivudine) and Triumeq (dolutegravir, abacavir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both Dovato and Triumeq contain dolutegravir and lamivudine and should not be taken with any other medicinal products also containing dolutegravir and lamivudine.

Dovato (dolutegravir/lamivudine) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

Dovato (dolutegravir/lamivudine) and Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Dovato (dolutegravir/lamivudine) and Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with additional lamivudine.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to raltegravir should be considered as coadministering two integrase inhibitors (i.e., raltegravir and dolutegravir) is unlikely to be of clinical benefit.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Triumeq contains abacavir and should not be taken with additional abacavir.

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. In addition, Triumeq (dolutegravir, abacavir, lamivudine) should not be taken with any other medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

Triumeq (dolutegravir, abacavir, lamivudine) and Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, Triumeq contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Triumeq (dolutegravir, abacavir, lamivudine) and Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, Triumeq contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine. Furthermore, coadministering two integrase inhibitors (i.e., elvitegravir and dolutegravir) is unlikely to be of clinical benefit.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Triumeq contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Triumeq contains lamivudine and should not be taken with additional lamivudine.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to raltegravir should be considered as coadministering two integrase inhibitors (i.e., raltegravir 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 must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and bictegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Genvoya (elvitegravir, cobicistat, 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. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and elvitegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV-1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and elvitegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Coadministration is not recommended as it may impair lenacapavir efficacy. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Coadministration with efavirenz (a moderate CYP3A4 and UGT inducer) decreased lenacapavir AUC and Cmax by 56% and 36%.

Coadministration has not been studied but is not recommended as it may impair lenacapavir efficacy. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4 and UGT1A1. Nevirapine induces CYP3A4. Coadministration with efavirenz (another moderate CYP3A4 and UGT inducer) decreased lenacapavir AUC and Cmax by 56% and 36%. A similar effect is expected with nevirapine.

The dolutegravir dose (50 mg) in Triumeq is insufficient when coadministered with some medications that may decrease dolutegravir concentrations. The European product label for Triumeq does not recommend coadministration with these medications. However, the US product label for Triumeq recommends that if additional dolutegravir is required, a dolutegravir 50 mg tablet, separated by 12 hours from Triumeq, should be taken.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with efavirenz is expected to decrease dolutegravir exposure. The European product label for Triumeq does not recommend coadministration with efavirenz. However, the US product label for Triumeq recommends that an additional dolutegravir 50 mg tablet, separated by 12 hours from Triumeq, should be taken. 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. Coadministration of lamivudine (150 mg twice daily) with efavirenz (600 mg once daily) increased lamivudine Cmin by 265%, but had no effect on lamivudine Cmax or AUC. Abacavir had no effect on efavirenz pharmacokinetics when abacavir, efavirenz and indinavir were coadministered. 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 (as an additional 50 mg tablet of dolutegravir administered approximately 12 hours after Triumeq) in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

Elvitegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less elvitegravir being absorbed. Divalent cations can be found in multivitamins. As the effect of cationic complexation cannot be excluded, it is recommended to separate the administration of elvitegravir/cobicistat and multivitamin preparations by at least 4 hours. Significant interactions are not expected with emtricitabine and tenofovir-DF.

Bictegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less bictegravir being absorbed. Divalent cations can be found in multivitamins. As the effect of cationic complexation cannot be excluded, it is recommended to administer bictegravir and multivitamins containing divalent cations simultaneously with food.

Coadministration has not been studied. As with other HIV integrase inhibitors, elvitegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced elvitegravir concentrations. Separating the administration of integrase inhibitors and ferrous fumarate by at least 4 hours is recommended. Significant interactions are not expected with cobicistat, emtricitabine and tenofovir-DF.

Caution is recommended when prescribing ferrous fumarate. Raltegravir binds to divalent cations such as iron and forms a complex at the level of the gastro-intestinal tract which results in less raltegravir being absorbed. The European product label for raltegravir states that taking iron salts at least two hours from the administration of raltegravir may allow to limit this effect. Note, drug-drug interaction studies with antacids containing divalent cations have shown a more pronounced reduction in raltegravir Cmin when raltegravir was administered once daily compared to a twice daily regimen. A similar effect for iron supplements cannot be excluded.

Genvoya (elvitegravir, cobicistat, 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 maraviroc (dosed at 150 mg twice daily) would be possible from a pharmacokinetic standpoint.

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 decreases lopinavir concentrations by 30-40%. Efavirenz should not be coadministered with once daily lopinavir/ritonavir. Lopinavir/ritonavir tablets should be increased to 500/125 mg twice daily; lopinavir/ritonavir oral solution should be increased to 533/133 mg twice daily. Monitor closely. TDM may be useful. Furthermore, a prolongation of the QT interval may occur with efavirenz treatment in carriers of CYP2B6*6/*6. Use with caution as both drugs have a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration decreased lopinavir AUC by 27%. Nevirapine should not be coadministered with once daily Lopinavir/ritonavir. Lopinavir/ritonavir tablets should be increased to 500/125 mg twice daily; lopinavir/ritonavir oral solution should be increased to 533/133 mg twice daily. Monitor closely. TDM may be useful.

Coadministration of efavirenz (600 mg once daily) and ritonavir (500 mg twice daily) increased the AUC of efavirenz (21%) and ritonavir (17%) and a higher frequency of adverse events (e.g., dizziness, nausea, paraesthesia) and laboratory abnormalities (elevated liver enzymes) were observed. The magnitude of the interaction is expected to be lower when ritonavir is dosed as a pharmacokinetic booster and is expected to result in a lower risk of adverse effects.

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. Nevirapine, an inducer of CYP3A4, could potentially decrease dolutegravir concentrations. The US Prescribing Information advises that coadministration should be avoided because there are insufficient data to make dosing recommendations. However, the European SPC recommends a dolutegravir dose of 50 mg twice daily with nevirapine, except in the presence of integrase class resistance when alternative combinations that do not include nevirapine should be considered.

Coadministration of ritonavir (100 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) increased lopinavir Cmax (28%) and AUC (46%), and Cmin (116%). Appropriate doses of additional ritonavir in combination with lopinavir/ritonavir with respect to safety and efficacy have not been established.

Coadministration has not been studied. Maraviroc is metabolized by CYP3A4. When coadministered with darunavir/cobicistat, maraviroc should be dosed at 150 mg twice daily. The European SmPC for maraviroc recommends when coadministering potent CYP3A inhibitors and maraviroc to patients with impaired renal function (creatinine clearance less than 80 ml/min), maraviroc should be reduced to 150 mg once daily. The US Prescribing Information recommends 150 mg twice daily for patients with creatinine clearance of 30-80 ml/min and contraindicates coadministration in patients with creatinine clearance less than 30 ml/min or on haemodialysis.

Coadministration of tenofovir-DF (300 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) had no significant effect on lopinavir/ritonavir PK parameters; tenofovir AUC increased by 32%, Cmin increased by 51%, and there was no change in Cmax. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir boosted protease inhibitor. No dose adjustment is recommended, but close monitoring of renal function and for tenofovir-associated adverse reactions is required.

Coadministration with ritonavir alone has not been studied. Coadministration of tenofovir-DF and ritonavir (100 mg twice daily with lopinavir, darunavir or saquinavir) had no significant effect on ritonavir concentrations. However, a higher risk of renal impairment has been reported in patients receiving tenofovir-DF in combination with a ritonavir boosted protease inhibitor. Close monitoring of renal function is required in these patients.

As with other HIV integrase inhibitors, bictegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced bictegravir concentrations. The simultaneous administration of ferrous fumarate (324 mg) and bictegravir with food did not significantly impair bictegravir exposure whereas exposure was decreased by 63% during simultaneous administration in fasted conditions. It is recommended to administer bictegravir and ferrous fumarate simultaneously with food.

Administration of ferrous fumarate (324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. Administer dolutegravir 2 hours before or 6 hours after ferrous fumarate. The US Prescribing information suggests that, alternatively, dolutegravir and supplements containing iron can be taken together with food. Medicinal products that reduce dolutegravir exposure (e.g. ferrous fumarate) should be avoided in the presence of integrase class resistance.

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No interaction is expected with lamivudine. Administration of ferrous fumarate (324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. When taken with food, Dovato and ferrous fumarate can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking ferrous fumarate.

Coadministration with Triumeq (dolutegravir/abacavir/lamivudine) has not been studied. No interaction is expected with abacavir or lamivudine. Administration of ferrous fumarate (324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. Triumeq and supplements containing iron can be taken together with food. If Triumeq is taken in a fasted state, iron supplements should be taken at least 2 hours after or 6 hours before Triumeq.

Coadministration has not been studied but darunavir/cobicistat is expected to increase tenofovir plasma concentrations (inhibition of P-gp). Darunavir/cobicistat and tenofovir disoproxil fumarate can be used without dose adjustments. However, monitoring of renal function may be indicated when darunavir/cobicistat is given in combination with tenofovir disoproxil fumarate, particularly in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents. 

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) 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 maraviroc (dosed at 150 mg twice daily) would be possible from a pharmacokinetic standpoint.

Coadministration has not been studied. As with other HIV integrase inhibitors, elvitegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced elvitegravir concentrations. Separating the administration of integrase inhibitors and ferrous fumarate by at least 4 hours is recommended. Significant interactions are not expected with cobicistat, emtricitabine and tenofovir alafenamide.

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No interaction is expected with lamivudine. Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir AUC by 33%. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Coadministration with dolutegravir/abacavir/lamivudine has not been studied. No interaction is expected with abacavir or lamivudine. Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir AUC by 33%. Triumeq and multivitamins can be taken together with food. If Triumeq is taken in a fasted state, multivitamins should be taken at least 2 hours after or 6 hours before Triumeq.

Decrease maraviroc dose to 150 mg twice daily when given with lopinavir/ritonavir or lopinavir/ritonavir/efavirenz. Coadministration of lopinavir/ritonavir (400/100 mg twice daily) and maraviroc (300 mg twice daily) increased maraviroc AUC (4.0-fold) and Cmax (2.0-fold). Lopinavir and ritonavir concentrations were not measured, but no effect is expected. The addition of efavirenz (600 mg once daily) to lopinavir/ritonavir/maraviroc reduced the increases in maraviroc AUC and Cmax to 2.5-fold and 1.3-fold, respectively. The European SmPC for maraviroc recommends when coadministering lopinavir/ritonavir and maraviroc to patients with impaired renal function (creatinine clearance less than 80 ml/min), maraviroc should be reduced to 150 mg once daily. The US Prescribing Information recommends 150 mg twice daily for patients with creatinine clearance of 30-80 ml/min and contraindicates coadministration in patients with creatinine clearance less than 30 ml/min or on haemodialysis.

Coadministration of ritonavir (100 mg twice daily) and a non-licensed dose of maraviroc (100 mg twice daily) increased maraviroc concentrations. The recommended dose of maraviroc when coadministered is 150 mg twice daily (except with tipranavir/ritonavir). The European SmPC for maraviroc recommends when coadministering potent CYP3A inhibitors and maraviroc to patients with impaired renal function (creatinine clearance less than 80 ml/min), maraviroc should be reduced to 150 mg once daily. The US Prescribing Information recommends 150 mg twice daily for patients with creatinine clearance of 30-80 ml/min and contraindicates coadministration in patients with creatinine clearance less than 30 ml/min or on haemodialysis.

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 lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration may increase bictegravir concentrations due to inhibition of CYP3A4 by lopinavir/ritonavir but this is unlikely to require dose modification. Coadministration of lopinavir/ritonavir and emtricitabine/tenofovir alafenamide had no significant effect on lopinavir and increased exposure of tenofovir alafenamide. 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.

The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with some medications that may decrease dolutegravir concentrations. An additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato (dolutegravir/lamivudine), is recommended with these medications.

Maraviroc dose should be increased to 600 mg twice daily when co-administered with efavirenz in the ABSENCE of a PI or other potent CYP3A4 inhibitor. Maraviroc dose should be decreased to 150 mg twice daily when co-administered with efavirenz in the PRESENCE of a PI (other than tipranavir/ritonavir where the dose should be 600 mg twice daily). Coadministration of efavirenz alone decreased maraviroc exposure by ~50%. Coadministration with a boosted PI increased maraviroc exposure by up to 5.0-fold. The US Prescribing Information contraindicates coadministration in patients with creatinine clearance less than 30 ml/min or on haemodialysis.

Dovato (dolutegravir/lamivudine) 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 efavirenz would be possible from a pharmacokinetic standpoint. The European product label for Dovato recommends an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato, during coadministration with efavirenz. Coadministration of dolutegravir and efavirenz decreased dolutegravir AUC, Cmax and Cmin by 57%, 39% and 75%, respectively. There was no change in efavirenz when compared to historical controls. Coadministration of lamivudine (150 mg twice daily) with efavirenz (600 mg once daily) increased lamivudine Cmin by 265%, but had no effect on lamivudine Cmax or AUC. 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 (as an additional 50 mg tablet of dolutegravir administered approximately 12 hours after Dovato) in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

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 of ritonavir-boosted darunavir (or indinavir) would be possible from a pharmacokinetic standpoint. Coadministration of bictegravir and darunavir/cobicistat increased bictegravir AUC by 74%. A comparable increase in bictegravir exposure is anticipated when coadministered with darunavir/ritonavir. 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, darunavir/ritonavir increases tenofovir alafenamide (the prodrug of tenofovir) due to inhibition of intestinal P-gp thereby increasing the systemic concentration. Coadministration of darunavir/ritonavir (800/100 mg once daily) and tenofovir alafenamide (10 mg once daily) increased tenofovir AUC and Cmax by 105% and 142%, 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.

Raltegravir binds to divalent cations such as iron, calcium, magnesium and forms a complex at the level of the gastro-intestinal tract which results in less raltegravir being absorbed. Coadministration of raltegravir (400 mg single dose) with a Forceval multivitamin tablet (containing 108 mg calcium, 12 mg iron and 30 mg magnesium) did not significantly affect the pharmacokinetics of raltegravir (Cmax, Cmin and AUC decreased by 12%, 10% and 17%, respectively). However, since the content of divalent cations is variable among multivitamins preparations, caution is recommended when prescribing multivitamins. Administration of raltegravir 400 mg twice daily and multivitamins should be separated by at least 6 hours. Importantly, drug-drug interaction studies with antacids containing divalent cations have shown a more pronounced reduction in raltegravir Cmin when raltegravir was administered once daily compared to a twice daily regimen. A similar effect for multivitamins containing divalent cations cannot be excluded, therefore, twice daily administration of raltegravir should be preferred.

Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. Medicinal products that reduce dolutegravir exposure (e.g. multivitamins) should be avoided in the presence of integrase class resistance.

Dovato (dolutegravir/lamivudine) 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 nevirapine would be possible from a pharmacokinetic standpoint. The European product label for Dovato recommends an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato, during coadministration as nevirapine, an inducer of CYP3A4, could potentially decrease dolutegravir concentrations. Note, the bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such as nevirapine oral suspension.

Elvitegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less elvitegravir being absorbed. Divalent cations can be found in multivitamins. As the effect of cationic complexation cannot be excluded, it is recommended to separate the administration of elvitegravir/cobicistat and multivitamin preparations by at least 4 hours. Significant interactions are not expected with emtricitabine and tenofovir alafenamide.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with nevirapine is not recommended. Nevirapine, an inducer of CYP3A4, could potentially decrease dolutegravir concentrations. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with nevirapine would be possible from a pharmacokinetic standpoint if an additional dolutegravir 50 mg tablet, separated by 12 hours from Triumeq, is taken. Note, the bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such as nevirapine oral suspension.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 94% and 130%. This increase is not considered to be clinically relevant and does not warrant a dose adjustment. A similar effect is expected with lopinavir/ritonavir.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 94% and 130%. This increase is not considered to be clinically relevant and does not warrant a dose adjustment. A similar effect is expected with ritonavir.

Coadministration has not been studied. Rilpivirine is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase rilpivirine, although to an extent that is not considered to be clinically relevant. No a priori dose adjustment is needed.

Triumeq (dolutegravir, abacavir, lamivudine) 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 lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration of lopinavir/ritonavir and dolutegravir decreased dolutegravir AUC and C24 by 4% and 6% and had no effect on Cmax; there was no effect on lopinavir or ritonavir. Coadministration of lopinavir/ritonavir and abacavir decreased abacavir AUC by 32%. No change in the pharmacokinetics of lopinavir was observed with lamivudine in clinical studies.

Triumeq (dolutegravir/abacavir/lamivudine) 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 maraviroc (dosed at 300 mg twice daily) would be possible from a pharmacokinetic standpoint. Maraviroc is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations and no interaction is expected with abacavir. Coadministration of maraviroc (300 mg twice daily) and lamivudine/zidovudine (150/300 mg twice daily) increased lamivudine AUC (14%) and Cmax (16%), but is not considered to be clinically significant. Maraviroc concentrations were not measured, but no effect is expected.

Genvoya (elvitegravir, cobicistat, 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 zidovudine would be possible from a pharmacokinetic standpoint.

Dovato (dolutegravir/lamivudine) 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 rilpivirine would be possible from a pharmacokinetic standpoint. 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 interaction is expected with lamivudine.

Triumeq (dolutegravir, abacavir, lamivudine) is indicted 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 rilpivirine would be possible from a pharmacokinetic standpoint. 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 interaction is expected with abacavir or lamivudine.

Triumeq (dolutegravir, abacavir, lamivudine) 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 ritonavir would be possible from a pharmacokinetic standpoint. Based on studies with boosted PIs, ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of ritonavir. No interaction is expected with abacavir or lamivudine.

Triumeq (dolutegravir, abacavir, lamivudine) can be used 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 tenofovir-DF would be possible from a pharmacokinetic standpoint. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir, abacavir or lamivudine. 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 significant pharmacokinetic interaction was observed when tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) were coadministered. There was no change in AUC, Cmax or Cmin of tenofovir. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax. Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) had no effect on tenofovir AUC or Cmax, and abacavir AUC; abacavir Cmax increased by 12%.

Triumeq (dolutegravir, abacavir, lamivudine) can be used 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 zidovudine would be possible from a pharmacokinetic standpoint. Coadministration of single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) showed no clinically relevant changes in the pharmacokinetics of abacavir. Lamivudine AUC decreased by 15% and zidovudine AUC increased by 10% with concurrent abacavir. No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed with coadministration of zidovudine (200 mg, single dose) and lamivudine (300 mg single dose).

Dovato (dolutegravir/lamivudine) 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 ritonavir would be possible from a pharmacokinetic standpoint. Based on studies with boosted PIs, ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of ritonavir. No interaction is expected with lamivudine.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and is not recommended in the Biktarvy product label. However, in specific clinical situations where an intensification of HIV treatment is needed, the coadministration of rilpivirine would be possible from a pharmacokinetic standpoint.

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 abacavir would be possible from a pharmacokinetic standpoint.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) 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 of rilpivirine would be possible from a pharmacokinetic standpoint. Coadministration is expected to increase rilpivirine concentrations however no dose adjustment is required.

Dovato (dolutegravir/lamivudine) 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 tenofovir-DF would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with tenofovir. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir or lamivudine. 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. Coadministration of tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) had no effect on AUC, Cmax or Cmin of tenofovir. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) 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 abacavir would be possible from a pharmacokinetic standpoint. Based on metabolism and clearance a clinically significant interaction with elvitegravir/cobicistat or emtricitabine is unlikely. Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) had no effect on abacavir AUC but Cmax increased by 12%. A similar increase in abacavir Cmax may occur with elvitegravir/cobicistat/emtricitabine/tenofovir-DF. 

Coadministration with Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bictegravir is metabolised by CYP3A4 and UGT1A1; emtricitabine and tenofovir alafenamide are eliminated renally. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4 and could potentially increase bictegravir, although to an extent that is not considered to be clinically relevant. No a priori dose adjustment is needed.

Dovato (dolutegravir/lamivudine) 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 zidovudine would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with zidovudine. No interaction is expected with dolutegravir. No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed with coadministration of zidovudine (200 mg, single dose) and lamivudine (300 mg single dose).

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infections. 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 is expected to increase rilpivirine concentrations however no dose adjustment is required.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) 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 zidovudine would be possible from a pharmacokinetic standpoint.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Coadministration of oral lenacapavir (300 mg single dose) and cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 128% and 110%. This increase is not considered to be clinically relevant. Lenacapavir is a weak inhibitor of P-gp and coadministration with tenofovir alafenamide (a P-gp substrate) increased tenofovir alafenamide exposure by 32% and the respective tenofovir exposure by 47%. This increase is not considered to be clinically relevant.

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 zidovudine would be possible from a pharmacokinetic standpoint.

Coadministration has not been studied. Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, P-gp and UGT1A1. Coadministration of oral lenacapavir (300 single dose) and cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 128% and 110%. This increase is not considered to be clinically relevant. Lenacapavir is a weak inhibitor of P-gp and coadministration with tenofovir alafenamide (a P-gp substrate) increased tenofovir alafenamide exposure by 32% and the respective tenofovir exposure by 47%. This increase is not considered to be clinically relevant. A similar effect is expected with tenofovir-DF.

Coadministration has not been studied. Lenacapavir is a weak inhibitor of P-gp and coadministration with tenofovir alafenamide (a P-gp substrate) increased tenofovir alafenamide exposure by 32% and the respective tenofovir exposure by 47%. This increase is not considered to be clinically relevant. A similar effect is expected with tenofovir-DF.

Coadministration of abacavir and lopinavir/ritonavir has no effect on lopinavir or ritonavir pharmacokinetics, but appears to decrease abacavir exposure by ~30%. The clinical significance of this is unknown.

Genvoya (elvitegravir, cobicistat, 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 abacavir would be possible from a pharmacokinetic standpoint.

Dovato (dolutegravir/lamivudine) 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 lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with lopinavir/ritonavir. Coadministration of lopinavir and dolutegravir decreased dolutegravir AUC and C24 by 4% and 6% and had no effect on Cmax; there was no effect on lopinavir or ritonavir. No change in the pharmacokinetics of lopinavir was observed with stavudine and lamivudine in clinical studies.

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 maraviroc dosed at 300 mg twice daily would be possible from a pharmacokinetic standpoint. Maraviroc is metabolized by CYP3A4, however, bictegravir does not inhibit or induce CYP450 enzymes. A pharmacokinetic interaction between maraviroc and emtricitabine or tenofovir alafenamide is not expected.

Lenacapavir is mainly cleared as unchanged drug and is a substrate of CYP3A4, UGT1A1 and P-gp. Coadministration of oral lenacapavir (300 mg single dose) with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased lenacapavir AUC and Cmax by 94% and 130%. This increase is not considered to be clinically relevant and does not warrant a dose adjustment.

Dovato (dolutegravir/lamivudine) 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 maraviroc (dosed at 300 mg twice daily) would be possible from a pharmacokinetic standpoint. Maraviroc is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of maraviroc (300 mg twice daily) and lamivudine/zidovudine (150/300 mg twice daily) increased lamivudine AUC (14%) and Cmax (16%), but is not considered to be clinically significant. Maraviroc concentrations were not measured, but no effect is expected.

Triumeq (dolutegravir, abacavir, lamivudine) 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 dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) decreased dolutegravir Cmax, AUC, and C24 by 11%, 16% and 19%, respectively (n=9). Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively, and cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. No interaction is expected with abacavir or lamivudine.

No dose adjustment is required when rilpivirine is co-administered with lopinavir/ritonavir. Coadministration of rilpivirine (150 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) increased rilpivirine Cmax, AUC and Cmin by 29%, 52% and 74%, respectively. Lopinavir Cmax, AUC and Cmin decreased by 4%, 1% and 11%, respectively. [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.] Both lopinavir and rilpivirine have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; possible risk for rilpivirine). Although the product label for lopinavir advises caution when prescribing lopinavir with medicinal products which have the potential to increase the QT interval, there is no anticipated increased risk of QT prolongation when combining these drugs. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with lopinavir/ritonavir.

Dovato (dolutegravir/lamivudine) 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 with abacavir is needed, dolutegravir and lamivudine are available coformulated with abacavir as a fixed dose combination (Triumeq).

Coadministration has not been studied. The coadministration of maraviroc dosed at 300 mg twice daily would be possible from a pharmacokinetic standpoint. Maraviroc is metabolized by CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a moderate inhibitor of CYP3A4, however, no a priori dose adjustment of maraviroc is needed in the absence of boosted antiretroviral agents.

Dovato (dolutegravir/lamivudine) 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 dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) decreased dolutegravir Cmax, AUC, and C24 by 11%, 16% and 19%, respectively (n=9). Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively, and cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. No interaction is expected with lamivudine.

No clinically significant interaction is expected with nevirapine and ritonavir dosed as a pharmacokinetic booster. Coadministration of nevirapine (200 mg twice daily) with ritonavir (600 mg twice daily) caused no alteration in ritonavir AUC, Cmax or Cmin. The effect on nevirapine pharmacokinetics was not significant.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely.

Coadministration has not been studied. Lopinavir/ritonavir induces glucuronidation and therefore has the potential to reduce zidovudine plasma concentrations. The clinical significance of this potential interaction is considered low.

No change in the pharmacokinetics of lopinavir was observed when lopinavir/ritonavir was given alone or in combination with stavudine and lamivudine in clinical studies.

Lamivudine metabolism does not involve CYP3A, making interactions with protease inhibitors unlikely.

Coadministration of ritonavir (300 mg four times daily) and zidovudine (200 mg three times daily) had no effect on ritonavir AUC, Cmax or Cmin, but decreased zidovudine AUC and Cmax by 25% and 27% respectively. Dose alterations should not be necessary.

Tenofovir and nevirapine plasma levels remain unchanged when co-administered. Tenofovir-DF and nevirapine can be co-administered without dose adjustments.

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.

Based on the results of in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low. The coadministration of emtricitabine, didanosine and efavirenz was studied in 9 treatment naive, HIV+ patients. When compared to historical data for each drug alone, the pharmacokinetics of emtricitabine were not affected, didanosine AUC and Cmax were higher than expected and efavirenz Cmax, Cmin and AUC were lower than expected. However, efavirenz concentrations may have been underestimated as dosing was delayed by 12 hours for ease of sampling.

Based on the results of in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low.

Based on the results of in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low. Nevirapine trough concentrations in 7 HIV+ subjects receiving nevirapine (200 mg twice daily) with tenofovir/emtricitabine were comparable to historical values.

Based on the results of in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low.

No significant pharmacokinetic interaction was observed in clinical studies. A high rate of virological failure and emergence of resistance reported when lamivudine was combined with tenofovir and abacavir as a once daily regimen. Note, the bioavailability of lamivudine solution has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such as abacavir oral solution.

Clinical studies have shown no clinically significant interactions between abacavir and zidovudine.

Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) had no effect on tenofovir AUC or Cmax, and abacavir AUC; abacavir Cmax increased by 12%. A high rate of virological failure and emergence of resistance have been reported when lamivudine was combined with tenofovir-DF and abacavir as a once daily regimen.

Coadministration of zidovudine (200 mg single dose) and lamivudine (300 mg twice daily) to 12 asymptomatic HIV-infected adult patients increased zidovudine Cmax and AUC by 28% and 13%. Zidovudine had no effect on the pharmacokinetics of lamivudine. No dose adjustments are necessary.

No significant pharmacokinetic interaction was observed when tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) were coadministered. There was no change in AUC, Cmax or Cmin of tenofovir. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax. High rate of virological failure and emergence of resistance reported when lamivudine was combined with tenofovir-DF and abacavir as a once daily regimen.

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

No significant interactions were observed between emtricitabine and 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.

No significant interactions were observed when emtricitabine (200 mg once daily for 7 days) and zidovudine (300 mg once daily for 7 days) was studied in 27 HIV-negative subjects.

No significant interaction expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

No significant interaction expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

Coadministration of maraviroc (300 mg twice daily) and lamivudine/zidovudine (150/300 mg twice daily) increased lamivudine AUC (14%) and Cmax (16%), but is not considered to be clinically significant. Maraviroc concentrations were not measured, but no effect is expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

Coadministration of maraviroc (300 mg twice daily) and tenofovir-DF (300 mg once daily) had no significant effect on maraviroc AUC or Cmax. Tenofovir concentrations were not measured, but no effect is expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

Coadministration of maraviroc (300 mg twice daily) and lamivudine/zidovudine (150/300 mg twice daily) had no effect on zidovudine AUC and decreased Cmax by 8%. Maraviroc concentrations were not measured, but no effect is expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

The recommended dose of maraviroc when coadministered with nevirapine is 300 mg twice daily. When compared to historical data, coadministration of a single dose of maraviroc (300 mg) to HIV+ subjects stable on a nevirapine containing regimen had no effect on maraviroc AUC and increased Cmax by 54%. Nevirapine concentrations were not measured, but no effect is expected.

Coadministration increased abacavir AUC and Cmax by 3% and 6%, respectively; Cmin decreased by 17%. Studies are required to relate the change in plasma abacavir exposure to the active intracellular carbovir triphosphate.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely.

In drug interaction studies, raltegravir (400 mg twice daily) did not have a clinically meaningful effect on the pharmacokinetics of lamivudine. No dose adjustment is required with twice daily or once daily raltegravir.

Coadministration of tenofovir-DF and raltegravir (400 mg twice daily) increased raltegravir AUC (49%) and Cmax (64%), but had no effect on Cmin; tenofovir AUC, Cmax and Cmin decreased by 10%, 23% and 13%, respectively. The safety profile observed in patients who used atazanavir and/or tenofovir-DF (both agents that increase raltegravir concentrations) was generally similar to that of patients who did not use these agents. No dose adjustment is required with twice daily or once daily raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of NNRTIs. No dose adjustment is required with twice daily or once daily raltegravir.

No dose adjustment is required when efavirenz is coadministered with twice daily or once daily raltegravir. Efavirenz (600 mg once daily) did not have a clinically meaningful effect on the pharmacokinetics of raltegravir. Coadministration with raltegravir (400 mg single dose) decreased raltegravir AUC, C12 and Cmax by 36%, 21% and 36%, respectively. Coadministration with raltegravir (1,200 mg single dose) decreased raltegravir AUC, C24 and Cmax by 14%, 6% and 9%, respectively.

Coadministration of raltegravir (400 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) had no effect on raltegravir AUC or Cmax (5.3 vs 5.4 mg/L.h and 1698 vs 1687 ng/ml, alone vs combination respectively) but decreased raltegravir Cmin by 30% (49.4 vs 34.4 ng/ml). Lopinavir and ritonavir pharmacokinetics were similar when given alone or with raltegravir. Raltegravir Cmin remained above the estimated IC95 of 15 ng/ml, suggesting that no dose adjustments are required for either drug.

Coadministration of raltegravir (400 mg single dose) and  low dose ritonavir had no significant effect on raltegravir pharmacokinetics (AUC decreased by 16%, Cmax decreased by 24%, no change in Cmin). No dose adjustment required for twice daily or once daily raltegravir.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely.

Coadministration of raltegravir (400 mg twice daily) and maraviroc (300 mg twice daily) decreased maraviroc AUC (14%), Cmax (21%) and Cmin (10%). Raltegravir AUC, Cmax and Cmin were decreased by 37%, 33% and 28%, respectively. The maraviroc average concentration was greater than 100 ng/ml (the apparent threshold for increased risk of virologic failure) in all subjects. The 28% decrease in raltegravir Cmin was not considered clinically relevant. No dose adjustments are required for twice daily or once daily raltegravir, or for maraviroc.

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with emtricitabine.

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

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

Coadministration has not been studied but based on very limited data for metabolism and clearance, a clinically significant interaction 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 needed for either drug. [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 relevant drug-drug interaction is expected when rilpivirine is co-administered with maraviroc.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of NNRTIs. No dose adjustment is required.

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with abacavir.

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with lamivudine.

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with zidovudine.

Coadministration has not been studied but may increase rilpivirine concentrations. However, no dose adjustment is required. Rilpivirine is not expected to affect the plasma concentrations of ritonavir.

Coadministration with ritonavir alone has not been studied. Based on studies with boosted PIs, ritonavir is not expected to significantly affect dolutegravir pharmacokinetics. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of ritonavir. No dosage adjustment is necessary.

Based on metabolism and clearance, a pharmacokinetic interaction is unlikely. [Dolutegravir is available coformulated with lamivudine for the treatment of HIV-1 infection where there is no known or suspected resistance to the integrase inhibitor class, or to lamivudine.]

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.

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. Maraviroc is metabolized by CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Lopinavir/ritonavir has no clinically significant effect on the pharmacokinetics of dolutegravir. Coadministration of lopinavir/ritonavir (400/100 mg twice daily) and dolutegravir (30 mg once daily had no effect on dolutegravir Cmax, and decreased AUC and Ctrough by 3% and 6%. Coadministration with lopinavir/ritonavir and etravirine had no significant effect on dolutegravir exposure (AUC, Cmax and Ctrough increased by 10%, 7% and 28%, respectively). When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of lopinavir or ritonavir. No dose adjustment is necessary.

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

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

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lenacapavir is mainly cleared as unchanged drug.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maraviroc is metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is mainly glucuronidated by UGT1A1. Cabotegravir does not inhibit or induce UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Efavirenz is a moderate inducer. Based on drug-drug interaction studies with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure is expected not to be clinically relevant. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dose adjustment is required with oral cabotegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nevirapine is a weak inducer. Based on drug-drug interaction studies with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure is expected not to be clinically relevant. No dose adjustment is required with oral cabotegravir. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) did not significantly alter cabotegravir and rilpivirine pharmacokinetics (n=11). Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively; rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively. No dose adjustment is required.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Coadministration of dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) decreased dolutegravir Cmax, AUC, and C24 by 11%, 16% and 19%, respectively (n=9). Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively, and cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. Dolutegravir and darunavir/cobicistat can be administered without dose adjustments.

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

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

Some clinical trials with darunavir/ritonavir suggest that raltegravir may cause a modest decrease in darunavir plasma concentrations however this effect does not appear to be clinically relevant. Raltegravir and darunavir/cobicistat can be administered without dose adjustments.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Darunavir/cobicistat do not inhibit UGT enzymes. Cabotegravir is not expected to alter concentrations of other antiretroviral products. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir used to boost lopinavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products. 

Coadministration has not been studied. Coadministration of rilpivirine and darunavir/cobicistat is expected to increase the plasma concentration of rilpivirine. However since the expected increase in rilpivirine concentrations is not considered clinically relevant, no dose adjustment is required when coadministering rilpivirine with darunavir/cobicistat. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as emtricitabine is primarily renally excreted. Darunavir/cobicistat is unlikely to inhibit OCTs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as lamivudine is primarily renally excreted. Darunavir/cobicistat is unlikely to inhibit OCTs at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as zidovudine is primarily renally excreted.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Both cabotegravir and lenacapavir do not have any inhibitory or inducing effects on UGT1A1 in the range of clinically significant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent CYP3A4. Lenacapavir is mainly cleared as unchanged drug and is a substrate of UGT1A1. Lenacapavir is a moderate inhibitor of CYP3A4, however, no significant effect is expected on dolutegravir as CYP3A4 plays a minor role in its metabolism. No interaction is expected with lamivudine and abacavir.