EPCLUSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPCLUSA (EPCLUSA).
EPCLUSA is a fixed-dose combination of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor. Sofosbuvir inhibits HCV RNA replication by acting as a chain terminator, while velpatasvir inhibits HCV replication by binding to NS5A and disrupting viral RNA replication and assembly.
| Metabolism | Sofosbuvir is metabolized in the liver to its active metabolite (GS-461203) via cathepsin A (CatA) and CES1, followed by phosphorylation. Velpatasvir is metabolized primarily by CYP2B6, CYP2C8, and CYP3A4. |
| Excretion | Sofosbuvir: 80% renal (as inactive metabolite GS-331007), 14% fecal; Velpatasvir: 94% fecal, 0.4% renal. |
| Half-life | Sofosbuvir: 0.4 hr (parent), 27 hr (GS-331007); Velpatasvir: 15 hr. Clinical context: once-daily dosing achieves steady-state in ~1 week. |
| Protein binding | Sofosbuvir: 61-65% (human plasma proteins); Velpatasvir: >99.5% (mainly albumin, alpha-1 acid glycoprotein). |
| Volume of Distribution | Sofosbuvir: ~69 L (calculated as Vd/F); Velpatasvir: ~130 L (calculated as Vd/F). Not typically expressed per kg; indicates extensive tissue distribution. |
| Bioavailability | Sofosbuvir: ~92% (oral, with food); Velpatasvir: ~25% (fasted), increased with high-fat meal (up to 2-fold). |
| Onset of Action | Oral: clinical effect (HCV RNA decline) detectable within 6 hours; maximal suppression by 2-4 weeks. |
| Duration of Action | Sustained virologic response (SVR) after 12-week course; duration of therapy 12-24 weeks depending on cirrhosis/ prior treatment. |
400 mg sofosbuvir / 100 mg velpatasvir orally once daily with or without food for 12 weeks.
| Dosage form | PELLETS |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Safety and efficacy not established for GFR <30 mL/min or hemodialysis; use with caution and consider alternative therapy. |
| Liver impairment | No dose adjustment for mild or moderate hepatic impairment (Child-Pugh A or B). Not recommended for use in severe hepatic impairment (Child-Pugh C) due to higher exposures of velpatasvir. |
| Pediatric use | For patients ≥6 years old or weighing ≥17 kg: fixed-dose combination (400 mg/100 mg) once daily with or without food, regardless of weight, for 12 weeks. Safety and efficacy not established for children <6 years or weighing <17 kg. |
| Geriatric use | No specific dose adjustment required based on age; use same dosing as younger adults, with monitoring for comorbidities and potential drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EPCLUSA (EPCLUSA).
| Breastfeeding | No data on the presence of sofosbuvir or velpatasvir in human milk, effects on the breastfed infant, or milk production. Because of the potential for adverse effects in the breastfed infant, breastfeeding is not recommended during treatment and for 6 months after the last dose, especially if ribavirin is co-administered. M/P ratio: unknown. |
| Teratogenic Risk | EPCLUSA (sofosbuvir/velpatasvir) is contraindicated in pregnancy due to the teratogenic risk associated with ribavirin (if used in combination). In the absence of ribavirin, there are no adequate human data; animal studies show no evidence of teratogenicity at clinically relevant exposures. However, due to the potential for ribavirin co-administration in some HCV regimens, pregnancy must be excluded before initiation and avoided during treatment and for 6 months after in females of childbearing potential. |
■ FDA Black Box Warning
Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV. Test all patients for evidence of current or prior HBV infection before initiating treatment. Monitor for HBV reactivation during and after treatment.
| Serious Effects |
["Concomitant use with amiodarone (risk of symptomatic bradycardia)","Concomitant use with strong P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort)"]
| Precautions | ["Risk of HBV reactivation in patients coinfected with HCV and HBV","Increased risk of bradycardia when used with amiodarone, especially in patients on beta-blockers or with cardiac comorbidities","Possible decreased therapeutic effect with strong P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort)","Not recommended in patients with severe renal impairment (eGFR <30 mL/min) or end-stage renal disease requiring dialysis"] |
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| Fetal Monitoring | Pregnancy testing before initiation, monthly during treatment, and 6 months after completion. Monitor liver function tests (LFTs) and HCV RNA levels periodically. In case of accidental exposure during pregnancy, report to the pregnancy registry (1-800-593-2214). |
| Fertility Effects | No effects on female or male fertility observed in animal studies. Ribavirin, if co-administered, causes significant teratogenicity and may impair spermatogenesis; males must use contraception for 6 months after treatment. |