Indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 kg who have no antiretroviral treatment history or 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 and no known substitutions associated with resistance to the individual components of GENVOYA.

GENVOYA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of GENVOYA have not been established in patients coinfected with human immunodeficiency virus-1 (HIV-1) and HBV.

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of GENVOYA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue GENVOYA. If appropriate, anti-hepatitis B therapy may be warranted.

Prior to or when initiating GENVOYA, test patients for hepatitis B virus infection.

Prior to or when initiating GENVOYA, and during treatment with GENVOYA 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.

GENVOYA is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).

GENVOYA is not recommended in patients with:

• severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute) or
• end stage renal disease (ESRD; estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis

Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products; while most of these cases were characterized by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events.

Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.

Prior to or when initiating GENVOYA, and during treatment with GENVOYA 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.

Discontinue GENVOYA in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including emtricitabine, a component of GENVOYA. Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of GENVOYA, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals.

GENVOYA is a complete regimen for the treatment of HIV-1 infection; therefore, co-administration of GENVOYA with other antiretroviral medications for treatment of HIV-1 infection should be avoided.

The concomitant use of GENVOYA and other drugs may result in known or potentially significant drug interactions, some of which may lead to:

• Loss of therapeutic effect of GENVOYA and possible development of resistance
• Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events, from greater exposures of concomitant drugs metabolized by CYP3A
• Loss of therapeutic effect of concomitant drugs that utilize CYP3A to form active metabolites

Co-administration 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.

Co-administration 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: Alfuzosin, Carbamazepine, Phenobarbital, Phenytoin, Rifampin, Lurasidone, Pimozide, Dihydroergotamine, Ergotamine, Methylergonovine, Cisapride, St. John’s wort, Lovastatin, Simvastatin, Sildenafila when dosed as REVATIO for the treatment of pulmonary arterial hypertension, Triazolam and orally administered Midazolam.

Co-administration 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.

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.

Separate GENVOYA and antacid administration by at least 2 hours.

GENVOYA is not recommended to be co-administered with colchicine to patients with renal or hepatic impairment.

Co-administration of GENVOYA with rifabutin or rifapentine is not recommended.

Initiation of GENVOYA in patients taking quetiapine: Consider alternative antiretroviral therapy to avoid increases in quetiapine exposure. If co-administration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions.

Co-administration 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.

Co-administration with corticosteroids whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression.

Co-administration 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.

Plasma concentrations of drospirenone may be increased when co-administered with cobicistat-containing products. Clinical monitoring is recommended due to the potential for hyperkalemia.

Co-administration of salmeterol and GENVOYA is not recommended.

Avoid use of tadalafil during the initiation of GENVOYA. Stop tadalafil at least 24 hours prior to starting GENVOYA.

Patients with CL_cr between 50 mL/minute and 60 mL/minute: The dosage of clarithromycin should be reduced by 50%.

When administering with GENVOYA, the maximum daily dosage of ketoconazole or itraconazole should not exceed 200 mg per day.

Clinical monitoring is recommended and a dosage decrease of the beta blocker may be necessary when these agents are coadministered with GENVOYA.

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 co-administered with cobicistat containing products. Clinical monitoring is recommended due to the potential for hyperkalemia.

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.

Careful monitoring of therapeutic and adverse effects of fentanyl (including potentially fatal respiratory depression) is recommended with co-administration.

A dose decrease may be needed for tramadol with concomitant use.

GENVOYA is not recommended for use during pregnancy because of substantially lower exposures of cobicistat and elvitegravir during the second and third trimesters.

GENVOYA should not be initiated in pregnant individuals. An alternative regimen is recommended for individuals who become pregnant during therapy with GENVOYA.

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.

GoToSource

• Chronic hepatitis B virus. GoToSource

• Use in pediatric patients weighing less than 25 kg. GoToSource

Kidney damage, decreased bone mineral density, fat redistribution, immune reconstitution syndrome, lactic acidosis (buildup of lactic acid in the blood), severe hepatomegaly with steatosis and increases in serum cholesterol. GoToSource

Hepatitis B flares. GoToSource

Liver injury. GoToSource

Tubulointerstitial nephritis (inflammation of tubules of kidneys and the tissues that surround them) and fulminant fanconi syndrome (disorder of kidney tubule function). GoToSource

Upper respiratory tract infection, bronchitis, influenza-like illness, diarrhea, musculoskeletal pain and sinusitis. GoToSource

Lawsuits filed for bone loss, kidney failure and lactic acidosis.