Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
Assessment of adverse reactions is based on clinical study data and postmarketing data. In pooled safety data from 2 controlled Phase 3 studies (GS-US-320-0108 and GS-US-320-0110; “Study 108” and “Study 110”, respectively), the most frequently reported adverse reactions at Week 96 analysis were headache (12%), nausea (6%), and fatigue (6%). After Week 96, patients either remained on their original blinded treatment up to Week 144 or received open-label tenofovir alafenamide.

The safety profile of tenofovir alafenamide was similar in virologically suppressed patients switching from tenofovir disoproxil to tenofovir alafenamide in Study 108, Study 110 and a controlled Phase 3 study GS-US-320-4018 (“Study 4018”). Changes in lipid laboratory tests were observed in these studies following a switch from tenofovir disoproxil (see section 5.1).

Tabulated summary of adverse reactions

The following adverse reactions have been identified with tenofovir alafenamide in patients with CHB (Table 2). The adverse reactions are listed below 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).

Table 2: Adverse Reactions Identified with Tenofovir Alafenamide

System organ class
Frequency            Adverse reaction
Nervous system disorders
Very common          Headache
Common               Dizziness
Gastrointestinal disorders
Common               Diarrhoea, vomiting, nausea, abdominal pain, abdominal distension, flatulence Hepatobiliary disorders
Common               Increased ALT
Skin and subcutaneous tissue disorders
Common               Rash, pruritus
Uncommon             Angioedema1, urticaria1
Musculoskeletal and connective tissue disorders
Common               Arthralgia
General disorders and administration site conditions
Common               Fatigue
1 Adverse reaction identified through post-marketing surveillance for tenofovir alafenamide-containing products.


In the open-label Phase 2 study (GS-US-320-4035; “Study 4035”) to evaluate the efficacy and safety of switching from another antiviral regimen to tenofovir alafenamide in virologically suppressed HBV infected patients, small median increases in fasting total cholesterol, direct low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides from baseline to Week 96 were observed in patients with moderate or severe renal impairment (Part A Cohort 1) and subjects with moderate or severe hepatic impairment (Part B), consistent with changes observed in Studies 108 and 110. Small median decreases in total cholesterol, LDL and triglycerides were observed in patientswith ESRD on hemodialysis in Part A Cohort 2, while small median increases were observed in HDL from baseline to Week 96. Median (Q1, Q3) change from baseline at Week 96 in total cholesterol to HDL ratio was 0.1 (-0.4, 0.4) in the moderate or severe renal impairment group, and -0.4 (-0.8,-0.1) in patientswith ESRD on hemodialysis and 0.1 (-0.2, 0.4) in patientswith moderate or severe hepatic impairment.

Metabolic parameters
Body weight and levels of blood lipids and glucose may increase during therapy.

Special populations
In Study 4035 in virologically suppressed patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault method 15 to 59 mL/min; Part A, Cohort 1, N = 78), end stage renal disease (ESRD) (eGFR < 15 mL/min) on haemodialysis (Part A, Cohort 2, N = 15), and/or moderate to severe hepatic impairment (Child-Pugh Class B or C at screening or by history; Part B, N = 31) who switched from another antiviral regimen to tenofovir alafenamide, no additional adverse reactions to tenofovir alafenamide were identified through Week 96.

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.

You can report any side effects to the Ministry of Health by clicking on the link "Report side effects due to medical treatment" that is located on the Ministry of Health homepage (www.health.gov.il) which redirects to the online form for reporting side effects or by clicking on the link: https://sideeffects.health.gov.il.


You can also report any side effects directly to the registration holder via email: Safety_FC@gilead.com .