Vosevi Adverse Reactions

Summary of the safety profile: In Phase 2 and 3 clinical trials, 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 postmarketing experience. All adverse reactions are presented in Table 14. The adverse reactions are listed as follows 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). (See Table 14.)

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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 Precautions and Interactions).
Skin disorders: Frequency not known: Stevens-Johnson syndrome.
Hepatobiliary disorders: Postmarketing experience: Hepatic decompensation, hepatic failure with NS3/4A protease inhibitor-containing regimens (see Precautions).
Laboratory abnormalities: Total bilirubin: In the Phase 3 trials 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. Healthcare professionals are asked to report any suspected adverse reactions.