Renal Considerations in Renally Impaired Adults

Renal laboratory parameters remained stable


Study 112: Impact on renal laboratory parameters at Week 96 in virologically suppressed adults with renal impairment who switched to GENVOYA®

Study 112: Change in eGFRCG at
Weeks 24 and 961

eGFR data are not included in the FDA-approved Prescribing Information. The long-term clinical significance of changes in eGFR is not known.


Selected renal laboratory parameters at Week 961-3

UPCR data are not included in the FDA-approved Prescribing Information.
The long-term clinical significance of changes in UPCR and its clinical relevance are not known.

  • 5 adults discontinued treatment due to the development of renal adverse events2
  • 1 additional adult with eGFR ≥50 mL/min developed acute renal failure. Following a brief interruption, GENVOYA was resumed and this adult's renal function returned to baseline2
See the Study 112 Study Design

Warnings and precautions (cont'd):

  • 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.

There were 0 cases of proximal renal tubulopathy or Fanconi syndrome observed in adults taking GENVOYA through Week 961,2

Adults with impaired renal function are at increased risk of renal-related adverse reactions. Otherwise, the safety profile of GENVOYA in adults in this study was similar to that in adults with normal renal function2

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 (10%), 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.

*Reflects full study population. N=248.

eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); UPCR, urine protein to creatinine ratio.

References:

  1. Data on file. Gilead Sciences, Inc.
  2. GENVOYA [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2017.
  3. Pozniak A, Arribas JR, Gathe J, et al; for GS-US-292-0112 Study Team. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-infected patients with renal impairment: 48-week results from a single-arm, multicenter, open-label phase 3 study. J Acquir Immune Defic Syndr. 2016;71(5):530-537.