genvoya

Testing: Prior to or when initiating GENVOYA test for hepatitis B virus infection. Prior to or when initiating GENVOYA, and during treatment on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. ( 2.1 ) Recommended dosage in adult and pediatric patients weighing at least 25 kg: One tablet taken orally once daily with food in patients with body weight at least 25 kg and a creatinine clearance greater than or equal to 30 mL per minute, or in adult patients with creatinine clearance less than 15 mL per minute who are receiving chronic hemodialysis. On days of hemodialysis, administer GENVOYA after hemodialysis. ( 2.2 ) Renal impairment: GENVOYA is not recommended in patients with estimated creatinine clearance of 15 to below 30 mL per minute, or below 15 mL per minute who are not receiving chronic hemodialysis. ( 2.3 ) Hepatic impairment: GENVOYA is not recommended in patients with severe hepatic impairment. ( 2.4 ) 2.1 Testing When Initiating and During Treatment with GENVOYA Prior to or when initiating GENVOYA, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1) ] . Prior to or when initiating GENVOYA, and during treatment with GENVOYA on a clinically appropriate schedule, assess serum…

The following adverse drug reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B [see Warnings and Precautions (5.1) ] Immune Reconstitution Syndrome [see Warnings and Precautions (5.3) ] New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.4) ] Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.5) ] Most common adverse reaction (incidence greater than or equal to 10%, all grades) is nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials in Treatment-Naïve Adults The primary safety assessment of GENVOYA was based on Week 144 pooled data from 1,733 subjects in two randomized, double-blind, active-controlled trials, Study 104 and Study 111, in antiretroviral treatment-naïve HIV-1 infected adult subjects. A total of 866 subjects received one tablet of GENVOYA once daily [see Clinical Studies (14.2) ] . The most common adverse reaction (all Grades) reported in at least 10% of…

Coadministration of GENVOYA is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These drugs and other contraindicated drugs (which may lead to reduced efficacy of GENVOYA and possible resistance) are listed below [see Drug Interactions (7.5) and Clinical Pharmacology (12.3) ] . Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine Herbal Products: St. John's wort ( Hypericum perforatum ) Lipid-modifying Agents: lomitapide, lovastatin, simvastatin Phosphodiesterase-5 (PDE-5) Inhibitor: sildenafil when administered as REVATIO ® for the treatment of pulmonary arterial hypertension Sedative/hypnotics: triazolam, orally administered midazolam Coadministration of GENVOYA is contraindicated with drugs that: Are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious adverse events. ( 4 ) Strongly induce CYP3A, which may lead to lower exposure of one or more components and loss of efficacy of GENVOYA and possible resistance. ( 4 )

No data are available on overdose of GENVOYA in patients. If overdose occurs, monitor the patient for evidence of toxicity. Treatment of overdose with GENVOYA consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Elvitegravir: Limited clinical experience is available at doses higher than the recommended dose of elvitegravir in GENVOYA. In one study, elvitegravir (administered with the CYP3A inhibitor cobicistat) equivalent to 2 times the therapeutic dose of 150 mg once daily for 10 days was administered to 42 healthy subjects. No severe adverse reactions were reported. The effects of higher doses are not known. As elvitegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Cobicistat: Limited clinical experience is available at doses higher than the recommended dose of cobicistat in GENVOYA. In two studies, a single dose of cobicistat 400 mg (2.7 times the dose in GENVOYA) was administered to a total of 60 healthy subjects. No severe adverse reactions were reported. The effects of higher doses are not known. As cobicistat is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Emtricitabine: Limited clinical experience is available at doses…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

GENVOYA should not be administered with other antiretroviral medications for treatment of HIV-1 infection. ( 7.1 ) GENVOYA can alter the concentration of drugs metabolized by CYP3A or CYP2D6. Drugs that induce CYP3A can alter the concentrations of one or more components of GENVOYA. Consult the full prescribing information prior to and during treatment for potential drug-drug interactions. ( 4 , 7.2 , 7.3 , 12.3 ) 7.1 Not Recommended with Other Antiretroviral Medications GENVOYA is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration of GENVOYA with other antiretroviral medications for treatment of HIV-1 infection should be avoided. Complete information regarding potential drug-drug interactions with other antiretroviral medications is not provided [see Contraindications (4) , Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . 7.2 Potential for GENVOYA to Affect Other Drugs Cobicistat, a component of GENVOYA, is an inhibitor of CYP3A and CYP2D6 and an inhibitor of the following transporters: P-glycoprotein (P-gp), BCRP, OATP1B1 and OATP1B3. Thus, coadministration of GENVOYA with drugs that are primarily metabolized by CYP3A or CYP2D6, or are substrates of P-gp, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs . Coadministration of GENVOYA with drugs that have active metabolite(s) formed by CYP3A may result in reduced plasma concentration of these active metabolite(s) (see Table 5 ). Elvitegravir is a modest inducer of CYP2C9 and may decrease the plasma concentrations of CYP2C9 substrates. TAF is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1. TAF is a weak inhibitor of CYP3A in vitro . TAF is not an inhibitor or inducer of CYP3A in vivo . 7.3 Potential for Other Drugs to Affect One or More Components of GENVOYA Elvitegravir and cobicistat, components of GENVOYA, are metabolized by CYP3A. Cobicistat is also metabolized, to a minor extent, by CYP2D6. 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 ). Coadministration of GENVOYA with other drugs that inhibit CYP3A may decrease the clearance and increase the plasma concentration of cobicistat. (see Table 5 ). TAF, a component of GENVOYA, is a substrate of P-gp, BCRP, OATP1B1 and OATP1B3. Drugs that inhibit P-gp and/or BCRP, such as cobicistat, may increase the absorption of TAF (see Table 13 ). However, when TAF is administered as a component of GENVOYA, its availability is increased by cobicistat and a further increase of TAF concentrations is not expected upon coadministration of an additional P-gp and/or BCRP inhibitor. Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF. 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. 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) ] . 7.5 Established and Other Potentially Significant Interactions Table 5 provides a listing of established or potentially clinically significant drug interactions [see Contraindications (4) ] . 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) ] . The table includes potentially significant interactions but is not all inclusive. Table 5 Established and Other Potentially Significant This table is not all inclusive. 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. Antiarrhythmics: e.g., amiodarone bepridil digoxin Indicates that a drug-drug interaction trial was conducted. 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. 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%. Anticoagulants: Direct Oral Anticoagulants (DOACs) apixaban rivaroxaban betrixaban dabigatran edoxaban ↑ apixaban Due to potentially increased bleeding risk, dosing recommendations for coadministration with GENVOYA depends on the apixaban dose. Refer to apixaban dosing instructions for coadministration with strong CYP3A and P-gp inhibitors in apixaban prescribing information. ↑ rivaroxaban ↑ betrixaban ↑ dabigatran ↑ edoxaban Coadministration of rivaroxaban with GENVOYA is not recommended because it may lead to an increased bleeding risk. Due to potentially increased bleeding risk, dosing recommendations for coadministration of betrixaban, dabigatran, or edoxaban with a P-gp inhibitor such as GENVOYA depends on DOAC indication and renal function. Refer to DOAC dosing instructions for coadministration with P-gp inhibitors in DOAC prescribing information. warfarin Effect on warfarin unknown Monitor the international normalized ratio (INR) upon coadministration of warfarin with GENVOYA. Anticonvulsants: carbamazepine phenobarbital phenytoin ↓ elvitegravir ↓ cobicistat ↓ TAF Coadministration with carbamazepine, phenobarbital, or phenytoin is contraindicated due to potential for loss of therapeutic effect and development of resistance. oxcarbazepine Alternative anticonvulsants should be considered when GENVOYA is administered with oxcarbazepine. ethosuximide ↑ ethosuximide Clinical monitoring is recommended upon coadministration of ethosuximide with GENVOYA. Antidepressants: Selective Serotonin Reuptake Inhibitors (SSRIs) e.g., paroxetine Tricyclic Antidepressants (TCAs) e.g., amitriptyline desipramine imipramine nortriptyline bupropion trazodone ↑ SSRIs (except sertraline) ↑ TCAs ↑ trazodone Careful dosage titration of the antidepressant and monitoring for antidepressant response are recommended when coadministered with GENVOYA. 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. Anti-gout: colchicine ↑ colchicine GENVOYA is not recommended to be coadministered with colchicine to patients with renal or hepatic impairment. Treatment of gout-flares – coadministration of colchicine in patients receiving GENVOYA: 0.6 mg (1 tablet) × 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Treatment course to be repeated no earlier than 3 days. Prophylaxis of gout-flares – coadministration of colchicine in patients receiving GENVOYA: If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day. Treatment of familial Mediterranean fever – coadministration of colchicine in patients receiving GENVOYA: Maximum daily dosage of 0.6 mg (may be given as 0.3 mg twice a day). Antimycobacterial: rifampin ↓ elvitegravir ↓ cobicistat ↓ TAF Coadministration with rifampin is contraindicated due to potential for loss of therapeutic effect and development of resistance. rifabutin rifapentine Coadministration of GENVOYA with rifabutin or rifapentine is not recommended. Antiplatelets: ticagrelor ↑ ticagrelor Coadminstration with ticagrelor is not recommended. clopidogrel ↓ clopidogrel active metabolite Coadministration with clopidogrel is not recommended due to protential reduction of the antiplatelet activity of clopidogrel. Antipsychotics: lurasidone ↑ lurasidone Coadministration with lurasidone is contraindicated due to potential for serious and/or life-threatening reactions. pimozide ↑ pimozide Coadministration with pimozide is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. quetiapine ↑ quetiapine Initiation of GENVOYA in patients taking quetiapine: Consider alternative antiretroviral therapy to avoid increases in quetiapine exposure. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring. Initiation of quetiapine in patients taking GENVOYA: Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine. Other antipsychotics e.g., perphenazine risperidone thioridazine ↑ antipsychotic A decrease in dose of the antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed when coadministered with GENVOYA. 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. 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. 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. Consider alternative corticosteroids. Coadministration with corticosteroids (all routes of administration) whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing's syndrome and adrenal suppression. 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. Endothelin Receptor Antagonists: bosentan ↑ bosentan Coadministration of bosentan in patients on GENVOYA: In patients who have been receiving GENVOYA for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. Coadministration of GENVOYA in patients on bosentan: Discontinue use of bosentan at least 36 hours prior to initiation of GENVOYA. After at least 10 days following the initiation of GENVOYA, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability. Ergot Derivatives: dihydroergotamine ergotamine methylergonovine ↑ ergot derivatives Coadministration is contraindicated due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues [see Contraindications (4) ] . Herbal Products: St. John's wort (Hypericum perforatum) ↓ elvitegravir ↓ cobicistat ↓ TAF Coadministration is contraindicated due to potential for loss of therapeutic effect and development of resistance . Hormonal Contraceptives: drospirenone/ethinyl estradiol levonorgestrel norgestimate/ethinyl estradiol ↑ drospirenone ↑ norgestimate ↑ levonorgestrel ↓ ethinyl estradiol Additional or alternative non-hormonal forms of contraception should be considered when estrogen based contraceptives are coadministered with GENVOYA. Plasma concentrations of drospirenone may be increased when coadministered with cobicistat-containing products. Clinical monitoring is recommended due to the potential for hyperkalemia. The effects of increases in the concentration of the progestational component norgestimate are not fully known and can include increased risk of insulin resistance, dyslipidemia, acne, and venous thrombosis. The potential risks and benefits associated with coadministration of norgestimate/ethinyl estradiol with GENVOYA should be considered, particularly in patients who have risk factors for these events. The effect of GENVOYA on other hormonal contraceptives (e.g., contraceptive patch, contraceptive vaginal ring, or injectable contraceptives) or oral contraceptives containing progestogens other than drospirenone, levonorgestrel, or norgestimate has not been studied; therefore, alternative (non-hormonal) methods of contraception can be considered. Immuno-suppressants: e.g., cyclosporine (CsA) sirolimus tacrolimus ↑ immuno-suppressants ↑ elvitegravir (with CsA) ↑ cobicistat (with CsA) Therapeutic monitoring of the immunosuppressive agents is recommended upon coadministration with GENVOYA. Monitor for adverse events associated with GENVOYA when coadministered with cyclosporine. 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. 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. Other Lipid-modifying Agents: lomitapide ↑ lomitapide Coadministration with lomitapide is contraindicated due to potential for markedly increased transaminases. Narcotic Analgesics: buprenorphine/ naloxone ↑ buprenorphine ↑ norbuprenorphine ↓ naloxone No dosage adjustment of buprenorphine/naloxone is required upon coadministration with GENVOYA. Patients should be closely monitored for sedation and cognitive effects. fentanyl ↑ fentanyl Careful monitoring of therapeutic and adverse effects of fentanyl (including potentially fatal respiratory depression) is recommended with coadministration. tramadol ↑ tramadol A dose decrease may be needed for tramadol with concomitant use. Inhaled Beta Agonist: salmeterol ↑ salmeterol Coadministration of salmeterol and GENVOYA is not recommended. Coadministration of salmeterol with GENVOYA may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia. Medications or Oral Supplements Containing Polyvalent Cations (e.g., Mg, Al, Ca, Fe, Zn): calcium or iron supplements, including multivitamins cation-containing antacids or laxatives sucralfate buffered medications ↓ elvitegravir Separate GENVOYA and administration of medications, antacids, or oral supplements containing polyvalent cations by at least 2 hours. Phosphodiesterase-5 (PDE5) Inhibitors: sildenafil tadalafil vardenafil ↑ PDE5 inhibitors Use of PDE-5 inhibitors for pulmonary arterial hypertension (PAH): Coadministration of sildenafil with GENVOYA is contraindicated when used for treatment of PAH, due to potential for PDE-5 inhibitor associated adverse reactions, including hypotension, syncope, visual disturbances, and priapism. The following dose adjustments are recommended for the use of tadalafil with GENVOYA: Coadministration of tadalafil in patients on GENVOYA: In patients receiving GENVOYA for at least 1 week, start tadalafil at 20 mg once daily. Increase tadalafil dose to 40 mg once daily based upon individual tolerability. Coadministration of GENVOYA in patients on tadalafil: Avoid use of tadalafil during the initiation of GENVOYA. Stop tadalafil at least 24 hours prior to starting GENVOYA. After at least one week following initiation of GENVOYA, resume tadalafil at 20 mg once daily. Increase tadalafil dose to 40 mg once daily based upon individual tolerability. Use of PDE-5 inhibitors for erectile dysfunction: Sildenafil at a single dose not exceeding 25 mg in 48 hours, vardenafil at a single dose not exceeding 2.5 mg in 72 hours, or tadalafil at a single dose not exceeding 10 mg in 72 hours can be used with increased monitoring for PDE-5 inhibitor associated with adverse events. 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. Coadministration of parenteral midazolam with GENVOYA should be done in a setting that ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. buspirone zolpidem With other sedative/hypnotics, dose reduction may be necessary and clinical monitoring is recommended. 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. Drug Interactions GENVOYA may interact with many drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or non-prescription medication or herbal products including St. John's wort [see Contraindications (4) and Drug Interactions (7) ] .