The GENVOYA (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) label was updated to include the:
Safety, efficacy and pharmacokinetic data (Week 48) in HIV-1 positive patients with End Stage Renal Disease (creatine clearance less below 15 mL per minutes) who are receiving chronic hemodialysis from the Phase 3b Study GS-US-292-1825 entitled “A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis.”
Addition of hypersensitivity reactions to the Postmarketing Experience Section (Section 6.2)
A summary of the changes includes the following:
2 DOSAGE AND ADMINISTRATION
2.2 Recommended Dosage
2.3 Not Recommended in Patients with Severe Renal Impairment
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
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Virologically-Suppressed Adults with End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis
The safety of GENVOYA in subjects with end stage renal disease (ESRD) (estimated creatinine clearance of less than 15 mL/min) on chronic hemodialysis was assessed in 55 subjects (Study 1825). The most commonly reported adverse reaction (adverse event assessed as causally related by investigator and all grades) was nausea (7%). Serious adverse events were reported in 53% of subjects and the most common serious adverse events were pneumonia (13%), fluid overload (7%), hyperkalemia (7%) and osteomyelitis (7%). Overall 5% of subjects permanently discontinued treatment due to an adverse event.
6.2 Postmarketing Experience
The following events have been identified during post approval use of products containing TAF, including GENVOYA. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders
Angioedema, urticaria, and rash
12 CLINICAL PHARMACOLOGY
Patients with Renal Impairment
The pharmacokinetics of GENVOYA in HIV-1 infected subjects with mild or moderate renal impairment (estimated creatinine clearance between 30 and 69 mL per minute by Cockcroft-Gault method), and in HIV-1 infected subjects with ESRD (estimated creatinine clearance of less than 15 mL per minute by Cockcroft-Gault method) receiving chronic hemodialysis were evaluated in subsets of virologically suppressed subjects in respective open-label trials, Study 112 and Study 1825. The pharmacokinetics of elvitegravir, cobicistat, and tenofovir alafenamide were similar among healthy subjects, subjects with mild or moderate renal impairment, and subjects with ESRD receiving chronic hemodialysis; increases in emtricitabine and tenofovir exposures in subjects with renal impairment were not considered clinically relevant.
14 CLINICAL STUDIES
Study 1825: Virologically-suppressed adults with end stage renal disease (ESRD) receiving chronic hemodialysis
In Study 1825, the efficacy and safety of GENVOYA once daily were evaluated in an open-label clinical trial of 55 virologically-suppressed (HIV-1 RNA less than 50 copies per mL for at least 6 months before switching to GENVOYA) HIV-1 infected subjects with ESRD (estimated creatinine clearance of less than 15 mL per minute by Cockcroft-Gault method) receiving chronic hemodialysis for at least 6 months.
Subjects had a mean age of 48 years (range 23–64), 76% were male, 82% were Black, 18% were White, and 15% identified as Hispanic/Latino. The mean baseline CD4+ cell count was 545 cell per mm3 (range 205–1473). At Week 48, 82% (45/55) maintained HIV-1 RNA less than 50 copies per mL after switching to GENVOYA. Two subjects had HIV-1 RNA ≥ 50 copies per mL by Week 48. Seven subjects discontinued the study drug due to AE or other reasons while suppressed. One subject did not have an HIV-1 RNA measurement at Week 48.
The updated label will soon be available at drugs@fda or DailyMed