Epclusa Adverse Reactions

Summary of the safety profile: In pooled Phase 3 clinical studies of patients with genotype 1, 2, 3, 4, 5 or 6 HCV infection the proportion of patients who permanently discontinued treatment due to adverse events was 0.2% and the proportion of patients who experienced any severe adverse events was 3.2% for patients receiving sofosbuvir/velpatasvir for 12 weeks. In clinical studies, headache, fatigue and nausea were the most common (incidence ≥10%) treatment emergent adverse events reported in patients treated with 12 weeks of sofosbuvir/velpatasvir. These and other adverse events were reported at a similar frequency in placebo treated patients compared with sofosbuvir/velpatasvir treated patients in the Phase 3 pivotal clinical studies.
Tabulated summary of adverse reactions: Assessment of adverse reactions for sofosbuvir/velpatasvir is based on safety data from clinical studies and postmarketing experience. All adverse reactions are presented in Table 18. 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 18.)

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Patients with decompensated cirrhosis: The safety profile of sofosbuvir/velpatasvir has been evaluated in one open-label study in which patients with CPT Class B cirrhosis received sofosbuvir/velpatasvir for 12 weeks (n = 90), sofosbuvir/velpatasvir + RBV for 12 weeks (n = 87) or sofosbuvir/velpatasvir for 24 weeks (n = 90). The adverse events observed were consistent with expected clinical sequelae of decompensated liver disease, or the known toxicity profile of ribavirin for patients receiving sofosbuvir/velpatasvir in combination with ribavirin.
Among the 87 patients who were treated with sofosbuvir/velpatasvir + RBV for 12 weeks, decreases in haemoglobin to less than 10 g/dL and 8.5 g/dL during treatment were experienced by 23% and 7% patients, respectively. Ribavirin was discontinued in 15% of patients treated with sofosbuvir/velpatasvir + RBV for 12 weeks due to adverse events.
Patients with renal impairment: The safety of sofosbuvir/velpatasvir has been evaluated in a 12-week non-controlled study including 59 subjects with ESRD requiring dialysis (Study 4062). In this setting, exposure of sofosbuvir metabolite GS-331007 was 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.
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.
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.