• Home
  • A-B index
  • Pharmacological Index
  • Drug Classes
  • Active Ingredients
  • Companies
  • News
  • Epclusa
    / Gilead


    Active Ingredient *
    Sofosbuvir 400 mg
    Velpatasvir 100 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    28

    partial basket chart 62097

    Dosage

    The recommended dose of this formulation is one tablet, taken orally, once daily with or without food.
    Recommended treatment and duration for all HCV genotypes (Includes patients co-infected with human immunodeficiency virus (HIV) and patients with recurrent HCV post-liver transplant):
    Patients without cirrhosis and patients with compensated cirrhosis: 
    Epclusa for 12 weeks.
    Addition of ribavirin may be considered for genotype 3 infected patients with compensated cirrhosis.
    Patients with decompensated cirrhosis: Epclusa + ribavirin for 12 weeks.
    When used in combination with ribavirin, refer also to the Physicians Leaflet of the medicinal product containing ribavirin.
    The following dosing is recommended where ribavirin is divided in two daily doses and given with food:
    Guidance for ribavirin dosing when administered with Epclusa to patients with decompensated cirrhosis:
    Child-Pugh-Turcotte (CPT) Class B cirrhosis pre-transplant: 
    1,000 mg ribavirin per day for patients < 75 kg and 1,200 mg for those weighing ≥ 75 kg.
    CPT Class C cirrhosis pre-transplant andCPT Class B or C post-transplant:
    Starting dose of 600 mg, which can be titrated up to a maximum of 1,000/1,200 mg (1,000 mg for patients weighing < 75 kg and 1,200 mg for patients weighing ≥ 75 kg) if well tolerated. If the starting dose is not well tolerated, the dose should be reduced as clinically indicated based on haemoglobin levels.
    If ribavirin is used in genotype 3 infected patients with compensated cirrhosis (pre- or post-transplant) the recommended dose of ribavirin is 1,000/1,200 mg (1,000 mg for patients weighing < 75 kg and 1,200 mg for patients weighing ≥ 75 kg).
    For ribavirin dose modifications, refer to the Physicians Leaflet of the medicinal product containing ribavirin.
    Patients should be instructed that if vomiting occurs within 3 hours of dosing an additional tablet of Epclusa should be taken. If vomiting occurs more than 3 hours after dosing, no further dose of Epclusa is needed.
    If a dose of Epclusa is missed and it is within 18 hours of the normal time, patients should be instructed to take the tablet as soon as possible and then patients should take the next dose at the usual time. If it is after 18 hours then patients should be instructed to wait and take the next dose of Epclusa at the usual time. Patients should be instructed not to take a double dose of Epclusa.
    Patients who have previously failed therapy with an NS5A-containing regimen: Epclusa + ribavirin for 24 weeks may be considered.
    Elderly: No dose adjustment is warranted for elderly patients.
    Renal impairment: No dose adjustment of Epclusa is required for patients with mild or moderate renal impairment. The safety and efficacy of Epclusa has not been assessed in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²) or end stage renal disease (ESRD)
    requiring haemodialysis.
    Hepatic impairment: No dose adjustment of Epclusa is required for patients with mild, moderate, or severe hepatic impairment (CPT Class A, B, or C). Safety and efficacy of Epclusa have been assessed in patients with CPT Class B cirrhosis, but not in patients with CPT Class C cirrhosis.
    Paediatric population: The safety and efficacy of Epclusa in children and adolescents aged less than 18 years have not yet been established. No data are available.
    Method of administration: For oral use. Patients should be instructed to swallow the tablet whole with or without food. Due to the bitter taste, it is recommended that the film-coated tablet is not chewed or crushed.


    Indications

    Treatment of chronic hepatitis C virus (HCV) infection in adults.


    Contra-Indications

    Hypersensitivity to the active substances or to any of the excipients.
    Use with potent P gp and potent CYP inducers: Medicinal products that are potent P glycoprotein (P-gp) or potent cytochrome P450 (CYP) inducers (rifampicin, rifabutin, St. John’s wort [Hypericum perforatum], carbamazepine, phenobarbital and phenytoin).  Co administration will significantly decrease sofosbuvir or velpatasvir plasma concentrations and could result in loss of efficacy of this formulation.


    Special Precautions

    Products containing sofosbuvir.
    Severe bradycardia and heart block: The concomitant use of amiodarone was limited through the clinical development of sofosbuvir plus DAAs. Cases are potentially life threatening, therefore amiodarone should only be used in patients on this formulation when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated.
    Patients who have previously failed therapy with an NS5A-containing regimen:  treatment with Epclusa + RBV for 24 weeks can be considered for patients who have failed therapy on an NS5A-containing regimen and who are deemed at high risk for clinical disease progression and who do not have alternative treatment options.
    Renal impairment: The safety of this formulation has not been assessed in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) or ESRD requiring haemodialysis.  When this formulation is used in combination with ribavirin refer also to the Physicians Leaflet for ribavirin for patients with creatinine clearance < 50 mL/min.
    Use with moderate P-gp inducers or moderate CYP inducers: Co-administration of such medicinal products with Epclusa is not recommended.
    Use with certain HIV antiretroviral regimens: Patients receiving Epclusa
    concomitantly with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovir-associated adverse reactions.
    Use in diabetic patients: Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV direct-acting antiviral treatment. Glucose levels of diabetic patients initiating direct-acting antiviral therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when direct-acting antiviral therapy is initiated.
    HCV/HBV (hepatitis B virus) co-infection: Cases of hepatitis B virus (HBV) reactivation, some of them fatal, have been reported during or after treatment with direct-acting antiviral agents. HBV screening should be performed in all patients before initiation of treatment. HBV/HCV co-infected patients are at risk of HBV reactivation, and should therefore be monitored and managed according to current clinical guidelines.
    CPT Class C cirrhosis: Safety and efficacy of this formulation has not been assessed in patients with CPT Class C cirrhosis.
    Liver transplant patients: The safety and efficacy of this formulation in the treatment of HCV infection in patients who are post-liver transplant have not been assessed.
    See prescribing information for full details.


    Side Effects

    Most common: Headache, fatigue and nausea.
    See prescribing information for full details.


    Drug interactions

    As this drug contains sofosbuvir and velpatasvir, any interactions that have been identified with these active substances individually may occur with this drug.
    Potential for this formulation to affect other medicinal products: Velpatasvir is an inhibitor of drug transporter P-gp, breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3. Co-administration of Epclusa with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products. See Table 3 at the attached doctor’s leaflet for examples of interactions with sensitive substrates of P-gp (digoxin), BCRP (rosuvastatin), and OATP (pravastatin).
    Potential for other medicinal products to affect this drug: Sofosbuvir and velpatasvir are substrates of drug transporters P-gp and BCRP. Velpatasvir is also a substrate of drug transporter OATP1B. In vitro, slow metabolic turnover of velpatasvir by CYP2B6, CYP2C8 and CYP3A4 was observed. Medicinal products that are potent inducers of P-gp or potent inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g. rifampicin, rifabutin, St. John’s wort, carbamazepine, phenobarbital and phenytoin) may decrease plasma concentrations of sofosbuvir or velpatasvir leading to reduced therapeutic effect of sofosbuvir/velpatasvir. The use of such medicinal products with Epclusa is contraindicated. Medicinal products that are moderate P-gp inducers or moderate CYP inducers (e.g. oxcarbazepine, modafinil or efavirenz) may decrease sofosbuvir or velpatasvir plasma concentration leading to reduced therapeutic effect of Epclusa.
    Co-administration with such medicinal products is not recommended with Epclusa.
    Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir or velpatasvir plasma concentrations. Medicinal products that inhibit OATP, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentration of velpatasvir. Clinically significant medicinal product interactions with Epclusa mediated by P-gp, BCRP, OATP, or CYP450 inhibitors are not expected; Epclusa may be co-administered with P-gp, BCRP, OATP and CYP inhibitors.
    Patients treated with vitamin K antagonists: As liver function may change during treatment with Epclusa, a close monitoring of International Normalised Ratio (INR) values is recommended.
    Interactions between Epclusa and other medicinal products: Please refer to Table 3 at the attached doctor’s leaflet.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of sofosbuvir, velpatasvir in pregnant women. As a precautionary measure, Epclusa use is not recommended during pregnancy.
    Lactation: It is unknown whether sofosbuvir, metabolites of sofosbuvir or velpatasvir are excreted in human milk. A risk to the newborns/infants cannot be excluded. Therefore, Epclusa should not be used during breast-feeding.
    See prescribing information for full details.


    Overdose

    The highest documented doses of sofosbuvir and velpatasvir were a single dose of 1,200 mg and a single dose of 500 mg, respectively. In these healthy volunteer studies, there were no untoward effects observed at these dose levels, and adverse events were similar in frequency and severity to those reported in the placebo groups. The effects of higher doses/exposures are not known.
    No specific antidote is available for overdose with this drug.  If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with  this formulation consists of general supportive measures including monitoring of vital signs, as well as observation of the clinical status of the patient. Haemodialysis can efficiently remove the predominant circulating metabolite of sofosbuvir, GS-331007, with an extraction ratio of 53%. Haemodialysis is unlikely to result in significant removal of velpatasvir, since velpatasvir is highly bound to plasma protein.


    Important notes

    Storage: Do not store above 30°C. After first opening, use within 1 month.


    Manufacturer
    Gilead Sciences Ireland UC, Ireland
    CLOSE