Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Severe bradycardia and heart block
Life-threatening cases of severe bradycardia and heart block have been observed when sofosbuvir containing regimens are used in combination with amiodarone. Bradycardia has generally occurred within hours to days, but cases with a longer time to onset have been observed mostly up to 2 weeks after initiating HCV treatment.

Amiodarone should only be used in patients on Vosevi 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 undergo cardiac monitoring in an in-patient setting for the first 48 hours of coadministration, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Due to the long half-life of amiodarone, cardiac monitoring as outlined above should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on Vosevi.

All patients with concurrent or recent use of amiodarone should 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 Vosevi 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.

Renal impairment

Safety data are limited in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) and ESRD requiring haemodialysis. Vosevi can be used in these patients with no dose adjustment when no other relevant treatment options are available (see sections 4.8, 5.1 and 5.2).

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) (see section 5.2).

Liver transplant patients

The safety and efficacy of Vosevi in the treatment of HCV infection in patients who are post-liver transplant have not been assessed. Treatment with Vosevi, in accordance with the recommended posology (see section 4.2), should be guided by an assessment of the potential benefits and risks for the individual patient.

Use with moderate P-gp inducers or moderate CYP inducers

Medicinal products that are moderate P-gp and/or moderate CYP inducers (e.g. efavirenz, modafinil, oxcarbazepine or rifapentine) may decrease sofosbuvir, velpatasvir and/or voxilaprevir plasma concentrations leading to reduced therapeutic effect of Vosevi. Co-administration of such medicinal products with Vosevi is not recommended (see section 4.5).

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 with Vosevi is not recommended (see section 4.5).

Use with certain HIV antiretroviral regimens

Vosevi 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 Vosevi and a pharmacokinetic enhancer has not been established. The potential risks and benefits associated with co-administration of Vosevi 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 Vosevi 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 Summary of Product Characteristics 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 treatment modified when necessary. The physician in charge of the diabetic care of the patient should be informed when DAA therapy is initiated.

Excipients

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose- galactose malabsorption should not take this medicinal product.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7    Effects on ability to drive and use machines

Vosevi has no or negligible influence on the ability to drive and use machines.