Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Effect on Concentration ↑ = Increase, ↓ = Decrease Clinical Comment Alpha 1-adrenoreceptor antagonist: alfuzosin ↑ alfuzosin Coadministration with alfuzosin is contraindicated due to potential for serious and/or life-threatening reactions such as hypotension.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Lipid-modifying Agents: HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Sedative/hypnotic: midazolam (oral) triazolam ↑ midazolam ↑ triazolam Coadministration with triazolam or orally administered midazolam is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Coadministration of triazolam or orally administered midazolam with GENVOYA may cause large increases in the concentrations of these benzodiazepines.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Lipid-modifying Agents: HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Sedative/hypnotic: midazolam (oral) triazolam ↑ midazolam ↑ triazolam Coadministration with triazolam or orally administered midazolam is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Coadministration of triazolam or orally administered midazolam with GENVOYA may cause large increases in the concentrations of these benzodiazepines.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Caution is warranted and clinical monitoring is recommended upon coadministration of calcium channel blockers with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
disopyramide flecainide systemic lidocaine mexiletine propafenone quinidine ↑ antiarrhythmics ↑ digoxin Caution is warranted and therapeutic concentration monitoring, if available, is recommended for antiarrhythmics when coadministered with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Caution is warranted and clinical monitoring is recommended upon coadministration of calcium channel blockers with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Caution is warranted and clinical monitoring is recommended upon coadministration of calcium channel blockers with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Caution is warranted and clinical monitoring is recommended upon coadministration of calcium channel blockers with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
The drug interactions described are based on studies conducted with either GENVOYA, the components of GENVOYA (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as individual agents and/or in combination, or are predicted drug interactions that may occur with GENVOYA [for magnitude of interaction, see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
atorvastatin ↑ atorvastatin Initiate atorvastatin with the lowest starting dose of atorvastatin and titrate carefully while monitoring for safety (e.g., myopathy). Do not exceed a dosage of atorvastatin 20 mg daily.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Antibacterials: clarithromycin telithromycin ↑ clarithromycin ↑ telithromycin ↑ cobicistat Patients with CL cr greater than or equal to 60 mL/minute: No dosage adjustment of clarithromycin is required. Patients with CL cr between 50 mL/minute and 60 mL/minute: The dosage of clarithromycin should be reduced by 50%.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Triazolam and orally administered midazolam are extensively metabolized by CYP3A.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Elvitegravir is a modest inducer of CYP2C9 and may decrease the plasma concentrations of CYP2C9 substrates. 7.3 Potential for Other Drugs to Affect One or More Components of GENVOYA Elvitegravir and cobicistat, components of GENVOYA, are metabolized by CYP3A. Drugs that induce CYP3A activity are expected to increase the clearance of elvitegravir and cobicistat, resulting in decreased plasma concentration of cobicistat, elvitegravir, and TAF, which may lead to loss of therapeutic effect of GENVOYA and development of resistance (see Table 5 ).
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Triazolam and orally administered midazolam are extensively metabolized by CYP3A.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
ethosuximide ↑ ethosuximide Clinical monitoring is recommended upon coadministration of ethosuximide with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Triazolam and orally administered midazolam are extensively metabolized by CYP3A.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Antifungals: itraconazole ketoconazole voriconazole ↑ elvitegravir ↑ cobicistat ↑ itraconazole ↑ ketoconazole ↑ voriconazole When administering with GENVOYA, the maximum daily dosage of ketoconazole or itraconazole should not exceed 200 mg per day.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Antifungals: itraconazole ketoconazole voriconazole ↑ elvitegravir ↑ cobicistat ↑ itraconazole ↑ ketoconazole ↑ voriconazole When administering with GENVOYA, the maximum daily dosage of ketoconazole or itraconazole should not exceed 200 mg per day.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone ↓ elvitegravir ↓ cobicistat ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to elvitegravir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Beta-Blockers: e.g., metoprolol timolol ↑ beta-blockers Clinical monitoring is recommended and a dosage decrease of the beta blocker may be necessary when these agents are coadministered with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone ↓ elvitegravir ↓ cobicistat ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to elvitegravir. Alternative corticosteroids including beclomethasone and prednisolone (whose PK and/or PD are less affected by strong CYP3A inhibitors relative to other studied steroids) should be considered, particularly for long-term use.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Antibacterials: clarithromycin telithromycin ↑ clarithromycin ↑ telithromycin ↑ cobicistat Patients with CL cr greater than or equal to 60 mL/minute: No dosage adjustment of clarithromycin is required.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.4 Drugs Affecting Renal Function Because emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of GENVOYA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. The drug interactions described are based on studies conducted with either GENVOYA, the components of GENVOYA (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as individual agents and/or in combination, or are predicted drug interactions that may occur with GENVOYA [for magnitude of interaction, see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Beta-Blockers: e.g., metoprolol timolol ↑ beta-blockers Clinical monitoring is recommended and a dosage decrease of the beta blocker may be necessary when these agents are coadministered with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone ↓ elvitegravir ↓ cobicistat ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to elvitegravir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Antifungals: itraconazole ketoconazole voriconazole ↑ elvitegravir ↑ cobicistat ↑ itraconazole ↑ ketoconazole ↑ voriconazole When administering with GENVOYA, the maximum daily dosage of ketoconazole or itraconazole should not exceed 200 mg per day. An assessment of benefit/risk ratio is recommended to justify use of voriconazole with GENVOYA.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
7.6 Drugs without Clinically Significant Interactions with GENVOYA Based on drug interaction studies conducted with the components of GENVOYA, no clinically significant drug interactions have been observed or are expected when GENVOYA is combined with the following drugs: famciclovir, famotidine, ledipasvir, methadone, omeprazole, prasugrel (active metabolite), sertraline, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide