Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) contains tenofovir alafenamide and must not be administered with other products containing tenofovir alafenamide.

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.

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.

Coadministration is contraindicated as it is expected to markedly increase simvastatin concentrations which may cause myopathy, including rhabdomyolysis.

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.

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. 

Coadministration has not been studied. Plasma concentrations of pravastatin could possibly increase when coadministered with elvitegravir/cobicistat possibly via inhibition of OATP1B1. In the absence of pharmacokinetic data but in light of a case report of rhabdomyolysis in a patient using elvitegravir/cobicistat and pravastatin/fenofibrate it is recommended to start with the lowest dose of pravastatin and titrate up to the desired clinical effect while monitoring for safety. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Concentrations of atorvastatin are increased when coadministered with Genvoya (elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide). Atorvastatin is metabolized by CYP3A4. Coadministration of atorvastatin (10 mg single dose) and elvitegravir/cobicistat (150/150 mg once daily, administered with emtricitabine and tenofovir alafenamide as Genvoya) was studied in 16 subjects. Elvitegravir Cmax, AUC and Cmin decreased by 9%, 8% and 12%, respectively. Atorvastatin Cmax and AUC increased by 132% and 160%. If the use of atorvastatin is considered necessary, start with the lowest dose of atorvastatin and titrate carefully while monitoring for safety. A daily dose of 40 mg atorvastatin should not be exceeded with careful safety monitoring. (Note, American treatment guidelines recommend a maximum daily dose of 20 mg for atorvastatin.) Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion (OAT1, OAT3 mediate methotrexate transport in the kidney whereas MRP4 and BCRP mediate methotrexate efflux in the urine). As methotrexate is a substrate of BCRP, concentrations may increase due to inhibition of BCRP by cobicistat, however, the clinical relevance of this is unknown. There is no risk for competition for active renal transport mechanisms as emtricitabine is eliminated by other renal transporters. Methotrexate can cause tubular toxicity, however, coadministration of both drugs is unlikely to be of concern as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

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.

Coadministration has not been studied but based on metabolism and clearance there is little potential for an interaction. Methotrexate is predominantly eliminated unchanged via the kidneys, with minimal metabolism. Results of a clinical study evaluating the co-administration of high-dose of intravenous methotrexate for chemotherapy and NNRTIs showed that methotrexate half-life was not prolonged. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

Coadministration of rilpivirine (150 mg once daily) and atorvastatin (40 mg once daily) decreased rilpivirine Cmax, AUC and Cmin by 9%, 10% and 10%, respectively. Atorvastatin Cmax and AUC increased by 35% and 4%; Cmin decreased by 15%. Cmax, AUC and Cmin of 2-hydroxy atorvastatin increased by 58%, 39% and 32%, whilst Cmax and AUC of 4-hydroxy atorvastatin increased by 28% and 23%. 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.]

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.]

Coadministration with Genvoya has not been studied. Coadministration of rosuvastatin (10 mg single dose) and elvitegravir/cobicistat (150/150 mg once daily) decreased elvitegravir Cmax and Cmin by 6% and 2%, and increased AUC by 2% (n=10). Rosuvastatin AUC and Cmax increased by 38% and 89%, respectively. The increase in rosuvastatin exposure is transient and not considered clinically relevant. No dose modification is required. Emtricitabine and tenofovir alafenamide do not interact with rosuvastatin metabolism.

Coadministration of rilpivirine (25 mg once daily) and tenofovir alafenamide (25 mg once daily) had no significant effect on the pharmacokinetics of rilpivirine (AUC and Cmin increased by 1% and 13%, Cmax decreased by 7%). Tenofovir alafenamide Cmax and AUC were unchanged. Tenofovir Cmax, AUC and Cmin increased by 13%, 11% and 18%, respectively. No dose adjustment of tenofovir alafenamide or rilpivirine is required.