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Severe bradycardia and heart block: Cases of severe bradycardia and heart block have been observed when sofosbuvir used in combination with another direct acting antiviral (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 Sofosbuvir and Velpatasvir tablets 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 Sofosbuvir and Velpatasvir tablets. 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 Sofosbuvir and Velpatasvir tablets.
All patients receiving Sofosbuvir and Velpatasvir tablets 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.
Patients who have previously failed therapy with an NS5A-containing regimen: There are no clinical data to support the efficacy of sofosbuvir/velpatasvir for the treatment of patients who have failed treatment with a regimen containing another NS5A inhibitor. However, on the basis of NS5A resistance associated variants (RAVs) typically seen in patients who have failed therapy with other NS5A inhibitor containing regimens, the in vitro pharmacology of velpatasvir, and the outcomes of sofosbuvir/velpatasvir treatment in NS5A-naïve patients with baseline NS5A RAVs enrolled into the ASTRAL-studies, treatment with Sofosbuvir and Velpatasvir tablets + 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: No dose adjustment of Sofosbuvir and Velpatasvir tablets is required for patients with mild or moderate renal impairment. The safety of Sofosbuvir and Velpatasvir tablets has not been assessed in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) or ESRD requiring haemodialysis. When Sofosbuvir and Velpatasvir tablets are used in combination with ribavirin refer also to the prescribing information for ribavirin for patients with creatinine clearance < 50 mL/min (see Pharmacology: Pharmacokinetics under Actions).
Use with moderate P-gp inducers or moderate CYP inducers: Medicinal products that are moderate P-gp or moderate CYP inducers (e.g. oxcarbazepine, modafinil or efavirenz) may decrease sofosbuvir or velpatasvir plasma concentrations leading to reduced therapeutic effect of Sofosbuvir and Velpatasvir tablets. Co-administration of such medicinal products with Sofosbuvir and Velpatasvir tablets is not recommended (see Interactions).
Use with certain HIV antiretroviral regimens: Sofosbuvir and Velpatasvir tablets have been shown to increase tenofovir exposure, especially 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 Sofosbuvir and Velpatasvir tablets and a pharmacokinetic enhancer has not been established. The potential risks and benefits associated with co-administration of Sofosbuvir and Velpatasvir tablets 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. atazanavir or darunavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving Sofosbuvir and Velpatasvir tablets 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.
HCV/HBV (hepatitis B virus) co-infection: There are no data on the use of Sofosbuvir and Velpatasvir tablets in patients with HCV/HBV co-infection. Clearance of HCV may lead to increased replication of HBV in patients who are HCV/HBV co-infected. HBV levels should be monitored during treatment with Sofosbuvir and Velpatasvir tablets, and during post-treatment follow-up.
CPT Class C cirrhosis: Safety and efficacy of Sofosbuvir and Velpatasvir tablets has not been assessed in patients with CPT Class C cirrhosis (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
Liver transplant patients: The safety and efficacy of Sofosbuvir and Velpatasvir tablets in the treatment of HCV infection in patients who are post-liver transplant have not been assessed. Treatment with Sofosbuvir and Velpatasvir tablets in accordance with the recommended posology (see Dosage & Administration) should be guided by an assessment of the potential benefits and risks for the individual patient. (See Table 16.)
Click on icon to see table/diagram/imageEffects on ability to drive and use machines: Sofosbuvir and Velpatasvir tablets has no or negligible influence on the ability to drive and use machines.
