Virso Special Precautions

General: VIRSO is not recommended for administration as monotherapy and should be prescribed in combination with other medicinal products for the treatment of hepatitis C infection. If the other medicinal products used in combination with VIRSO are permanently discontinued, VIRSO should also be discontinued (see Recommended dose under Dosage & Administration and Instruction for Use under Cautions for Usage). Consult the Summary of Product Characteristics for co prescribed medicinal products before starting therapy with VIRSO.
Severe bradycardia and heart block: Cases of severe bradycardia and heart block have been observed when sofosbuvir is used in combination with another direct-acting antiviral (DAAs, including daclatasvir, simeprevir and ledipasvir) and concomitant amiodarone with or without other drugs 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 VIRSO and another DAA when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.
Should concomitant use of amiodarone be considered necessary it is recommended that patients are closely monitored when initiating VIRSO and another DAA. 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 VIRSO in combination with and another DAA.
All patients receiving VIRSO and another DAA in combination with amiodarone with or without other drugs 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.
Treatment-experienced patients with genotype 1 and 4 HCV infection: Sofosbuvir has not been studied in a Phase 3 study in treatment experienced patients with genotype 1 and 4 HCV infection. The optimal treatment duration in this population has not been established (see also Recommended dose under Dosage & Administration, Instruction for Use under Cautions for Usage and Pharmacology: Pharmacodynamics under Actions).
Consideration should be given to treating these patients, and potentially extending the duration of therapy with sofosbuvir, peginterferon alfa and ribavirin beyond 12 weeks and up to 24 weeks; especially for those subgroups who have one or more factors historically associated with lower response rates to interferon based therapies (advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non-CC genotype).
Treatment of patients with genotype 5 or 6 HCV infection: There is very limited data regarding the use of Sofosbuvir in patients with genotype 5 and 6 HCV infection (see Pharmacology: Pharmacodynamics under Actions). Available data on subjects with genotype 5 or 6 HCV infection are insufficient for dosing recommendations.
Interferon-free therapy for genotype 1 HCV infection: Interferon free regimens for patients with genotype 1 HCV infection with sofosbuvir have not been investigated in Phase 3 studies (see Pharmacology: Pharmacodynamics under Actions). The optimal regimen and treatment duration have not been established. Such regimens should only be used for patients that are intolerant to or ineligible for interferon therapy, and are in urgent need of treatment.
Co-administration with other direct-acting antivirals against HCV: VIRSO should only be co administered with other direct acting antiviral medicinal products if the benefit is considered to outweigh the risks based upon available data. There are no data to support the co administration of sofosbuvir and telaprevir or boceprevir. Such co administration is not recommended (see also Interactions).
Use with moderate P-gp inducers: Medicinal products that are moderate P-gp inducers in the intestine (e.g. oxcarbazepine and modafinil) may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of VIRSO. Co administration of such medicinal products is not recommended with sofosbuvir (see Interactions).
Renal impairment: The safety of sofosbuvir has not been assessed in subjects with severe renal impairment (eGFR <30 mL/min/1.73 m²) or ESRD requiring haemodialysis. Furthermore, the appropriate dose has not been established. When VIRSO is used in combination with ribavirin or peginterferon alfa/ribavirin, refer also to the Summary of Product Characteristics for ribavirin for patients with creatinine clearance (CrCl) <50 mL/min (see also Pharmacology: Pharmacokinetics under Actions).
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.
Post-liver transplant patients: The safety and efficacy of VIRSO have not been established in post-liver transplant patients.
Use in Pregnancy: Pregnancy and concomitant use with ribavirin: When VIRSO is used in combination with ribavirin or peginterferon alfa/ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and for a period of time after the treatment as recommended in the Summary of Product Characteristics for ribavirin. Refer to the Summary of Product Characteristics for ribavirin for additional information.
Use in Children: VIRSO is not recommended for use in children and adolescents under 18 years of age because the safety and efficacy have not been established in this population.
Use in Elderly: Clinical studies of sofosbuvir included 65 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. In general, caution should be exercised when administering sofosbuvir in elderly patients reflecting the greater frequency of anaemia, decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
Effect on ability to drive and use machine: Sofosbuvir has moderate influence on the ability to drive and use machines. Patients should be informed that fatigue and disturbance in attention, dizziness and blurred vision have been reported during treatment with sofosbuvir in combination with peginterferon alfa and ribavirin.