Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

In Phase 2 and 3 clinical studies, the proportion of patients who permanently discontinued treatment due to adverse reactions was 0.1% for patients receiving sofosbuvir/velpatasvir/voxilaprevir for 8 weeks. There were no patients receiving sofosbuvir/velpatasvir/voxilaprevir for 12 weeks who permanently discontinued treatment due to adverse reactions in the Phase 2 and 3 pivotal clinical studies.

Tabulated summary of adverse reactions

Assessment of adverse reactions for Vosevi is based on safety data from clinical studies and post- marketing experience. All adverse reactions are presented in Table 3. The adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000) or very rare (< 1/10,000).

Table 3: Adverse reactions identified with Vosevi
Frequency            Adverse reaction
Nervous system disorders:
Very common          headache
Gastrointestinal disorders:
Very common          diarrhoea, nausea
Common               abdominal pain, decreased appetite, vomiting
Skin and subcutaneous tissue disorders:
Common               rash
Uncommon             angioedemaa
Musculoskeletal and connective tissue disorders:
Common               myalgia
Uncommon             muscle spasm
Laboratory investigations:
Common               total bilirubin increased a. Adverse reaction identified through post-marketing surveillance for sofosbuvir/velpatasvir-containing products 

Description of selected adverse reactions

Cardiac arrhythmias
Cases of severe bradycardia and heart block have been observed when sofosbuvir containing regimens are used in combination with amiodarone and/or other medicinal products that lower heart rate (see sections 4.4 and 4.5).

Skin disorders
Frequency not known: Stevens-Johnson syndrome

Laboratory abnormalities
Total bilirubin
In the Phase 3 studies increases in total bilirubin less than or equal to 1.5 x the upper limit of normal were observed in 4% of patients without cirrhosis and 10% of patients with compensated cirrhosis, due to inhibition of OATP1B1 and OATP1B3 by voxilaprevir. Total bilirubin levels decreased after completing Vosevi treatment.

Patients with renal impairment

The safety of sofosbuvir in a fixed dose combination with either ledipasvir or velpatasvir has been studied in 154 patients with ESRD requiring dialysis (Study 4062 and Study 4063). In this setting, exposure of sofosbuvir metabolite GS-331007 is 20-fold increased, exceeding levels where adverse reactions have been observed in preclinical trials. In this limited clinical safety data set, the rate of adverse events and deaths was not clearly elevated from what is expected in ESRD patients.
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: DrugSafety.Israel@gilead.com.