CONTRAINDICATIONS & DDIs

Components of GENVOYA® can interact with other drugs1


Contraindications

Cobicistat, a component of GENVOYA, is an inhibitor of and is metabolized by CYP3A and CYP2D6. Elvitegravir is metabolized by CYP3A. Other drugs similarly metabolized when coadministered with GENVOYA can result in an increase or decrease of their plasma concentration levels. GENVOYA is contraindicated with these drugs due to a potential for serious and/or life-threatening events or loss of efficacy and development of possible resistance to GENVOYA.1

GENVOYA is contraindicated for coadministration with the following drugs1
Drug class Drug name
Alpha 1-adrenoreceptor antagonist Alfuzosin
Anticonvulsants Carbamazepine,* phenobarbital, phenytoin
Antimycobacterial Rifampin
Antipsychotics Lurasidone, pimozide
Ergot derivatives Dihydroergotamine, ergotamine, methylergonovine
GI motility agent Cisapride
Herbal products St. John’s wort
HMG-CoA reductase inhibitors Lovastatin, simvastatin
Phosphodiesterase-5 (PDE5) inhibitor Sildenafil when dosed as Revatio® for the treatment of pulmonary arterial hypertension
Sedative/hypnotics Triazolam, orally administered midazolam

*Indicates that a drug-drug interaction trial was conducted.
See Drug Interactions (7), Table 5 in full Prescribing Information for sildenafil when used for erectile dysfunction.
See Drug Interactions (7), Table 5 in full Prescribing Information for parenterally administered midazolam.

Drug interactions1

Drug interactions* Clinical considerations
CYP3A substrates GENVOYA can alter the concentration of drugs metabolized by CYP3A or CYP2D6. Do not use with drugs highly dependent on these factors for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events.
CYP3A inducers Drugs that induce CYP3A can decrease the concentrations of components of GENVOYA. Do not use with drugs that strongly induce CYP3A as this may lead to loss of efficacy and possible resistance to GENVOYA.
P-gp Drugs that inhibit CYP3A, P-gp, or BCRP can increase the plasma concentrations of components of GENVOYA. Drugs that induce CYP3A or P-gp can decrease the plasma concentrations of components of GENVOYA.
Drugs affecting renal function Coadministration of GENVOYA with drugs that reduce renal fuction or compete for active tubular secretion may increase concentrations of emtricitabine and tenofovir and the risk of adverse reactions.
Antacids Separate GENVOYA and antacid administration by at least 2 hours.

*This table is not all-inclusive.


Drug interactions

  • 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.


Consult the full Prescribing Information for GENVOYA for more information on potentially significant drug interactions, including clinical comments.


GENVOYA is a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products.1

Emtricitabine and tenofovir, components of GENVOYA, are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion. Drugs that reduce renal function or compete for active tubular secretion should not be administered with GENVOYA because they may increase concentrations of emtricitabine and tenofovir and the risk of adverse reactions.1

Important Safety Information

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • 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.

Contraindications

  • 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: In all patients, monitor serum creatinine, serum phosphorus, CrCl, urine glucose, and urine protein prior to initiating and during therapy as clinically appropriate. 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.

Adverse reactions

  • Common adverse reactions (incidence ≥5%; all grades) in clinical studies were nausea (11%), diarrhea (7%), headache (6%), and fatigue (5%).

Drug interactions

  • 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.

Indication

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.

View full Prescribing Information for GENVOYA and DESCOVY® including BOXED WARNINGS.

Reference:

  1. GENVOYA [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2017.