Vemlidy Adverse Reactions

Summary of the safety profile: Assessment of adverse reactions is based on pooled safety data from 2 controlled Phase 3 studies (GS-US-320-0108 and GS-US-320-0110; "Study 108" and "Study 110", respectively) in which 866 HBV infected viremic patients with elevated serum ALT levels received 25 mg tenofovir alafenamide once daily in a double-blind fashion through Week 96 (median duration of blinded study drug exposure of 104 weeks) and from post-marketing experience. The most frequently reported adverse reactions were headache (12%), nausea (6%), and fatigue (6%). After Week 96, patients either remained on their original blinded treatment or received open-label tenofovir alafenamide. Changes in lipid laboratory tests were observed in Study 108 and Study 110. No additional adverse reactions to tenofovir alafenamide were identified from Week 96 through Week 144 in the double-blind phase and in the subset of subjects receiving open-label tenofovir alafenamide treatment (see Pharmacology: Pharmacodynamics under Actions).
In an ongoing double-blind, randomized, active-controlled study (GS-US-320-4018; "Study 4018") in virologically suppressed subjects who switched from tenofovir disoproxil to 25 mg tenofovir alafenamide (N=243), changes in lipid laboratory tests were observed. No additional adverse reactions to tenofovir alafenamide were identified through Week 48.
Tabulated summary of adverse reactions: The following adverse drug reactions have been identified with tenofovir alafenamide in patients with chronic hepatitis B (Table 8). The adverse reactions are listed as follows by body system organ class and frequency based on the Week 96 analysis. Frequencies are defined as follows: very common (≥1/10), common (≥1/100 to <1/10) or uncommon (≥1/1,000 to <1/100). (See Table 8.)

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Changes in lipid laboratory tests: In a pooled analysis of Studies 108 and 110, median changes in fasting lipid parameters from baseline to Week 96 were observed in both treatment groups. In the tenofovir alafenamide group, decreases in median fasting total cholesterol and HDL, and increases in median fasting direct LDL and triglycerides were observed, while the tenofovir disoproxil group demonstrated median reductions in all parameters (see Table 4). In patients randomised initially to tenofovir alafenamide and switched to receive open-label tenofovir alafenamide at Week 96, the median (Q1, Q3) changes from double-blind baseline to Week 144 were as follows (mg/dL): total cholesterol was 0 (-16, 18); LDL was 8 (-6, 24); HDL was -5 (-12, 2); triglycerides were 11 (-11, 40); total cholesterol to HDL ratio was 0.3 (0.0, 0.7). In patients randomised initially to tenofovir disoproxil and switched to open-label tenofovir alafenamide at Week 96, the median (Q1, Q3) changes from double-blind baseline to Week 144 were as follows (mg/dL): total cholesterol was 1 (-17, 20); LDL was 9 (-5, 26); HDL was -8 (-15, -1); triglycerides were 14 (-10, 43); total cholesterol to HDL ratio was 0.4 (0.0, 1.0).
In the open-label phase of Studies 108 and 110, where patients switched to open-label tenofovir alafenamide at Week 96, lipid parameters at Week 144 in patients who remained on tenofovir alafenamide were similar to those at Week 96, whereas median increases in fasting total cholesterol, direct LDL, HDL, and triglycerides were observed in patients who switched from tenofovir disoproxil to tenofovir alafenamide at Week 96. In the open label phase, median (Q1, Q3) change from Week 96 to Week 144 in total cholesterol to HDL ratio was 0.0 (-0.2, 0.4) in patients who remained on tenofovir alafenamide and 0.2 (-0.2, 0.6) in patients who switched from tenofovir disoproxil to tenofovir alafenamide at Week 96.
In Study 4018, median changes in fasting lipid parameters from baseline to Week 48 were observed in both treatment groups. In the group that switched from tenofovir disoproxil to tenofovir alafenamide, increases in median fasting total cholesterol, LDL, HDL, and triglycerides were observed, while the group continuing treatment with tenofovir disoproxil demonstrated reductions in median fasting total cholesterol, HDL, and triglycerides, and a minimal median increase in LDL (p < 0.001 for the difference between treatment groups in all parameters). Median (Q1, Q3) change from baseline at Week 48 in total cholesterol to HDL ratio was 0.2 (-0.1, 0.5) in the tenofovir alafenamide group and 0.0 (-0.3, 0.3) in the tenofovir disoproxil group (p < 0.001 for the difference between treatment groups).
Metabolic parameters: Body weight and levels of blood lipids and glucose may increase during therapy.
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.