Important Safety Information
BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF
- 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 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 (FTC) 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.
- Coadministration: Do not use with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Do not use with drugs that strongly induce CYP3A as this may lead to loss of efficacy and possible resistance to GENVOYA. Do not use with alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, lurasidone, pimozide, dihydroergotamine, ergotamine, methylergonovine, cisapride, lovastatin, simvastatin, sildenafil for pulmonary arterial hypertension, triazolam, oral midazolam, or St. John's wort.
Warnings and precautions
- Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during GENVOYA therapy and monitor for adverse reactions.
- Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
- New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of GENVOYA, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate GENVOYA in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue GENVOYA in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
Renal monitoring: Prior to and during therapy, as clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients, and also assess serum phosphorus in patients with chronic kidney disease. If serum creatinine increases >0.4 mg/dL from baseline, closely monitor for renal safety.
- Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue GENVOYA if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
- Common adverse reactions (incidence ≥5%; all grades) in clinical studies were nausea (11%), diarrhea (7%), headache (6%), and fatigue (5%).
- Prescribing information: Consult the full prescribing information for GENVOYA for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
- Metabolism: GENVOYA can increase the concentration of drugs metabolized by CYP3A, CYP2D6, P-gp, BCRP, OATP1B1, or OATP1B3. Drugs that inhibit CYP3A, P-gp, or BCRP can increase the concentrations of components of GENVOYA. Drugs that induce CYP3A or P-gp can decrease the concentrations of components of GENVOYA.
- Drugs affecting renal function: Coadministration of GENVOYA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.
Dosage and administration
- Dosage: Patients 12 years and older who weigh ≥35 kg: 1 tablet taken orally once daily with food.
- Renal impairment: Not recommended in patients with CrCl <30 mL/min.
- Hepatic impairment: Not recommended in patients with severe hepatic impairment.
- Testing prior to initiation: Test patients for HBV infection.
- Testing prior to initiation and during treatment: Assess serum creatinine, serum phosphorus, CrCl, urine glucose, and urine protein as clinically appropriate.
Pregnancy and lactation
- Pregnancy: There is insufficient human data on the use of GENVOYA during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
- Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.
GENVOYA is indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years and older (≥35 kg) who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in patients who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen for ≥6 months with no history of treatment failure and no known resistance to any component of GENVOYA.