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  • Vosevi 400 mg/100 mg/100 mg
    / 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

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    Related information


    Dosage

    WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS
    COINFECTED WITH HCV AND HBV
    Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Vosevi. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAA) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

    The recommended dose of this drug is one tablet, taken orally, once daily with food.
    Recommended treatment durations for this drug for all HCV genotypes (DAA: direct-acting antiviral agent):
    DAA naïve patients without cirrhosis: 8 weeks.
    DAA naïve patients with compensated cirrhosis:  12 weeks, 8 weeks may be considered in genotype 3 infected patients.
    DAA experienced patients* without cirrhosis or with compensated cirrhosis: 12 weeks.
    *In clinical trials the DAA experienced patients had been exposed to combination regimens containing any of the following: daclatasvir, dasabuvir, elbasvir, grazoprevir, ledipasvir, ombitasvir, paritaprevir, sofosbuvir, velpatasvir, voxilaprevir (administered with sofosbuvir and velpatasvir for less than 12 weeks).
    Missed dose: If a dose of the drug  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 at the usual time. Patients should be instructed not to take a double dose of the drug.
    Patients should be instructed that if vomiting occurs within 4 hours of dosing an additional tablet should be taken. If vomiting occurs more than 4 hours after dosing, no further dose of the drug is needed.
    Elderly: No dose adjustment is warranted for elderly patients.
    Renal impairment: No dose adjustment is required for patients with mild or moderate renal impairment. The safety and efficacy of this drug 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 is required for patients with mild hepatic impairment (Child-Pugh-Turcotte [CPT] Class A). This drug is not recommended in patients with moderate or severe hepatic impairment (CPT Class B or C).
    Paediatric population: The safety and efficacy of this drug in children and adolescents aged less than 18 years have not yet been established. No data are available.
    See prescribing information for full details.


    Indications

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


    Contra-Indications

    Hypersensitivity to the active substances or to any of the excipients.
    Concomitant use with medicinal products that are strong P-glycoprotein (P-gp) and/or strong cytochrome P450 (CYP) inducers (e.g. rifampicin, rifabutin, St. John’s wort [Hypericum perforatum], carbamazepine, phenobarbital and phenytoin).
    Concomitant use with rosuvastatin or dabigatran etexilate.
    Concomitant use with ethinylestradiol-containing medicinal products such as combined oral contraceptives or contraceptive vaginal rings.


    Special Precautions

    Severe bradycardia and heart block: Cases of severe bradycardia and heart block have been observed when sofosbuvir used in combination with another DAA, is used with concomitant amiodarone with or without other medicinal products that lower heart rate. The mechanism is not established.
    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 drug when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated.
    Should concomitant use of amiodarone be considered necessary, it is recommended that patients are closely monitored when initiating this drug.  Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for 48 hours in an appropriate clinical setting.
    Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on this drug.
    All patients receiving this drug in combination with amiodarone with or without other medicinal products that lower heart rate should also be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.
    HCV/HBV co-infection: There are no data on the use of this drug in patients with HCV/hepatitis B virus (HBV) co-infection. Cases of HBV reactivation, some of them fatal, have been reported during or after treatment with DAAs. HBV screening should be performed in all patients before initiation of treatment. HCV/HBV co-infected patients are at risk of HBV reactivation, and should therefore be monitored and managed according to current clinical guidelines.
    Hepatic impairment: No dose adjustment of Vosevi is required for patients with mild hepatic impairment (CPT Class A). Vosevi is not recommended in patients with moderate or severe hepatic impairment (CPT Class B or C).
    Liver transplant patients: The safety and efficacy of this drug in the treatment of HCV infection in patients who are post-liver transplant have not been assessed.
    Use with strong OATP1B inhibitors: Medicinal products that are strong OATP1B inhibitors (e.g. ciclosporin) may substantially increase voxilaprevir plasma concentrations, the safety of which has not been established. Co-administration of strong OATP1B inhibitors is not recommended.
    Use with certain HIV antiretroviral regimens: This agent has been shown to increase tenofovir exposure when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir disoproxil fumarate in the setting of this drug and a pharmacokinetic enhancer has not been established. The potential risks and benefits associated with co-administration of this drug with the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. darunavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving this drug 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. Refer to tenofovir disoproxil fumarate, emtricitabine/tenofovir disoproxil fumarate, or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate Prescribing Information for recommendations on renal monitoring.
    Use in diabetic patients: Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV DAA treatment. Glucose levels of diabetic patients initiating DAA 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 DAA therapy is initiated.
    See prescribing information for full details.


    Side Effects

    Very common: Headache, diarrhea, nausea.
    Common:
     Abdominal pain, decreased appetite, vomiting, rash, myalgia, total bilirubin increased.
    See prescribing information for full details.


    Drug interactions

    Potential for this drug to affect other medicinal products: Velpatasvir and voxilaprevir are inhibitors of drug transporters P-gp, breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3. Co-administration of this drug with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products. Medicinal products that are sensitive substrates of these transporters and for which elevated plasma levels are associated with serious events are contraindicated . Dabigatran etexilate (P-gp substrate) and rosuvastatin (OATP1B and BCRP substrate) are contraindicated.
    Potential for other medicinal products to affect this drug: Sofosbuvir, velpatasvir and voxilaprevir are substrates of drug transporters P-gp and BCRP. Velpatasvir and voxilaprevir are substrates of drug transporters OATP1B1 and OATP1B3. slow metabolic turnover of velpatasvir primarily by CYP2B6, CYP2C8 and CYP3A4 and of voxilaprevir primarily by CYP3A4 was observed.
    Medicinal products that may decrease plasma exposure of this drug:
    Medicinal products that are strong inducers of P-gp or strong inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g. rifampicin, rifabutin, St. John’s wort, carbamazepine, phenobarbital and phenytoin) may decrease plasma concentrations of sofosbuvir, velpatasvir and/or voxilaprevir leading to reduced therapeutic effect of this drug. The use of such medicinal products with this drug is contraindicated.
    Medicinal products that are moderate P-gp inducers or moderate CYP inducers (e.g. oxcarbazepine, rifapentine, modafinil or efavirenz) may decrease sofosbuvir, velpatasvir and/or voxilaprevir plasma concentrations leading to reduced therapeutic effect of this drug. Co-administration with such medicinal products is not recommended.
    Medicinal products that may increase plasma exposure of this drug: Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir, velpatasvir or voxilaprevir plasma concentrations. Medicinal products that inhibit OATP1B, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentrations of velpatasvir or voxilaprevir. The use of strong inhibitors of OATP1B (e.g. ciclosporin) with this drug is not recommended. Clinically significant medicinal product interactions with this drugmediated by P-gp, BCRP and CYP inhibitors are not expected. This drug may be co-administered with P-gp, BCRP and CYP inhibitors.
    Pharmacodynamic interactions
    Patients treated with vitamin K antagonists: As liver function may change during treatment with Vosevi, close monitoring of International Normalised Ratio (INR) values is recommended.
    Impact of DAA therapy on drugs metabolized by the liver: The pharmacokinetics of drugs that are metabolized by the liver (e.g. immunosuppressive agents such as calcineurin inhibitors) may be impacted by changes in liver function during DAA therapy, related to clearance of HCV.
    Patients treated with ethinylestradiol-containing medicinal products: Concomitant use with ethinylestradiol-containing medicinal products may increase the risk of alanine aminotransferase (ALT) elevations and is contraindicated.
    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, voxilaprevir or this drug in pregnant women. As a precautionary measure, Vosevi use is not recommended during pregnancy.
    LactationIt is unknown whether sofosbuvir, metabolites of sofosbuvir, velpatasvir or voxilaprevir are excreted in human milk. A risk to the newborns/infants cannot be excluded. Therefore, Vosevi should not be used during breast-feeding.
    See prescribing information for full details.


    Overdose

    The highest documented doses of sofosbuvir, velpatasvir and voxilaprevir were single doses of 1,200 mg, 500 mg, and 900 mg, respectively. In healthy volunteer studies with sofosbuvir and velpatasvir, 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 most common adverse reactions in patients receiving voxilaprevir 900 mg were diarrhoea (34%), nausea (17%) and headache (9%).
    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 drug 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 or voxilaprevir since velpatasvir and voxilaprevir are highly bound to plasma proteins.


    Important notes

    Storage: No special storage conditions, recommended to store at room temperature.


    Manufacturer
    Gilead Sciences Ireland UC, Ireland
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