Biktarvy Adverse Reactions

Summary of the safety profile: The assessment of adverse reactions is based on safety data from across all Phase 2 and 3 studies with Biktarvy and from post-marketing experience. In clinical studies of treatment-naïve patients receiving Biktarvy, the most frequently reported adverse reactions in the double-blind phase (Week 144) were headache (5%), diarrhoea (5%) and nausea (4%).
Tabulated summary of adverse reactions: The adverse reactions in Table 3 are listed by system organ class and frequency. Frequencies are defined as follows: common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000). (See Table 3.)

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Description of selected adverse reactions: Metabolic parameters: Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see Precautions).
Immune Reactivation Syndrome: In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see Precautions).
Osteonecrosis: Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see Precautions).
Changes in serum creatinine: Bictegravir has been shown to increase serum creatinine due to inhibition of tubular secretion of creatinine, however these changes are not considered to be clinically relevant since they do not reflect a change in glomerular filtration rate. Increases in serum creatinine occurred by Week 4 of treatment and remained stable through Week 144. In Studies GS-US-380-1489 and GS-US-380-1490, median (Q1, Q3) serum creatinine increased by 0.11 (0.03, 0.19) mg/dL (9.7 [2.7, 16.8] μmol/L), 0.11 (0.04, 0.19) mg/dL (9.7 [3.5, 16.8] μmol/L), and 0.12 (0.06, 0.21) mg/dL (10.6 [5.3, 18.6] μmol/L) from baseline to Week 144 in the Biktarvy, abacavir/dolutegravir/lamivudine, and dolutegravir + emtricitabine/tenofovir alafenamide groups, respectively. There were no discontinuations due to renal adverse events through Week 144 in patients administered Biktarvy in clinical studies.
Changes in bilirubin: In Studies GS-US-380-1489 and GS-US-380-1490, total bilirubin increases were observed in 17% of treatment-naïve patients administered Biktarvy through Week 144. Increases were primarily Grade 1 (12%) and Grade 2 (4%) (≥1.0 to 2.5 x Upper Limit of Normal [ULN]), and were not associated with hepatic adverse reactions or other liver-related laboratory abnormalities. Five patients administered Biktarvy (1%) had grade 3 bilirubin increases that were not considered related to study drug. There were no discontinuations due to hepatic adverse events through Week 144 in Biktarvy clinical studies.
Other special populations: Patients co-infected with hepatitis B: In 16 HIV/HBV co-infected adults administered Biktarvy (8 HIV/HBV treatment-naïve adults in Study GS-US-380-1490; 8 HIV/HBV suppressed adults in Study GS-US-380-1878), the safety profile of Biktarvy was similar to that in patients with HIV-1 monoinfection (see Pharmacology: Pharmacodynamics under Actions).
Elderly: Studies GS-US-380-1844, GS-US-380-1878 and the dedicated Study GS-US-380-4449 in patients ≥65 years old (evaluation of 86 HIV-1 infected, virologically-suppressed subjects ≥65 years old) included 111 patients aged ≥65 years who received Biktarvy. In these patients, no differences in the safety profile of Biktarvy were observed.
Patients with renal impairment: The safety of emtricitabine + tenofovir alafenamide was evaluated in a single arm, open-label clinical study (GS-US-292-1825), in which 55 virologically-suppressed HIV-1 infected patients with end stage renal disease (eGFR_CG <15 mL/min) on chronic haemodialysis received emtricitabine + tenofovir alafenamide in combination with elvitegravir + cobicistat as a fixed-dose combination tablet for 96 weeks. In an extension phase of Study GS-US-292-1825, 10 patients switched to Biktarvy for 48 weeks. No additional adverse reactions were identified in patients with end stage renal disease on chronic haemodialysis in this study (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Post-marketing experience: In addition to adverse reactions from clinical studies, the following adverse reactions were identified during post-approval use of products containing tenofovir alafenamide (TAF). Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
Renal and urinary disorders: Acute renal failure, proximal renal tubulopathy, Fanconi syndrome.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.