sofosbuvir, velpatasvir and voxilaprevir
Regulatory sources consulted
Approved indications
- Treatment of chronic HCV infection in adults without cirrhosis or with compensated cirrhosis, whether treatment-naive or previously treated with direct-acting antivirals, according to genotype and treatment history.
Contraindications
Absolute
- Hypersensitivity to sofosbuvir, velpatasvir, voxilaprevir, or excipients.
- Concomitant strong P-gp or CYP inducers such as carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin, or St John’s wort.
- Concomitant rosuvastatin, dabigatran, or ethinyl-estradiol-containing medicines.
Clinical warnings
- Assess HBV before starting because of reactivation risk. — CIMA/AEMPS, ficha técnica 1171223001
- Amiodarone may cause severe bradycardia; use only when no alternative exists and with monitoring. — CIMA/AEMPS, ficha técnica 1171223001
- It is not recommended in Child-Pugh B or C or in people with prior decompensation; hepatic decompensation and failure have been reported. — DailyMed, set_id 17ffc094-8ca7-45d2-80d8-fd043bc9a221
Drug interactions
- HighAmiodarone
Mechanism: It may cause potentially fatal bradycardia or heart block.
Recommendation: Use only when no alternative exists and monitor intensively.
CIMA/AEMPS, ficha técnica 1171223001
- HighStatins and transporter substrates
Mechanism: Voxilaprevir increases exposure of several substrates.
Recommendation: Review contraindications and dose limits for each statin.
CIMA/AEMPS, ficha técnica 1171223001
Adverse events
Common (≥1%)
Headache, diarrhea, and nausea
Rare but serious
HBV reactivation, severe bradycardia, and hepatic decompensation
Pregnancy and lactation
It is preferable to avoid during pregnancy and not use during breastfeeding.
Recent literature (PubMed)
The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS. NCT04695769. HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether riba