Sofosbuvir and Velpatasvir interacts in the following cases:
Safety data are limited in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²) and end stage renal disease (ESRD) requiring haemodialysis. Sofosbuvir/velpatasvir can be used in these patients with no dose adjustment when no other relevant treatment options are available.
Antacids e.g. aluminium or magnesium hydroxide; calcium carbonate.
It is recommended to separate antacid and Epclusa administration by 4 hours.
H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.
Co-administration with proton pump inhibitors is not recommended. If it is considered necessary to co-administer, then sofosbuvir/velpatasvir should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.
Clinical monitoring, looking for signs of bleeding and anaemia, is recommended when dabigatran etexilate is co-administered with sofosbuvir/velpatasvir. A coagulation test helps to identify patients with an increased bleeding risk due to increased dabigatran exposure.
Co-administration of sofosbuvir/velpatasvir with digoxin may increase the concentration of digoxin. Caution is warranted and therapeutic concentration monitoring of digoxin is recommended when co-administered with sofosbuvir/velpatasvir.
Co-administration of sofosbuvir/velpatasvir with oxcarbazepine is expected to decrease the concentration of sofosbuvir and velpatasvir, leading to reduced therapeutic effect of sofosbuvir/velpatasvir. Co-administration is not recommended.
Co-administration of sofosbuvir/velpatasvir with rifapentine is expected to decrease the concentration of sofosbuvir and velpatasvir, leading to reduced therapeutic effect of sofosbuvir/velpatasvir. Co-administration is not recommended.
Co-administration of sofosbuvir/velpatasvir with rosuvastatin increases the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis. Rosuvastatin, at a dose that does not exceed 10 mg, may be administered with sofosbuvir/velpatasvir.
Sofosbuvir/velpatasvir has 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/velpatasvir and a pharmacokinetic enhancer has not been established. The potential risks and benefits associated with co-administration of sofosbuvir/velpatasvir 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/velpatasvir 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.
The safety and efficacy of sofosbuvir/velpatasvir in the treatment of HCV infection in patients who are post-liver transplant have not been assessed. Treatment with sofosbuvir/velpatasvir in accordance with the recommended posology should be guided by an assessment of the potential benefits and risks for the individual patient.
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of sofosbuvir, velpatasvir or sofosbuvir/velpatasvir in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
It has not been possible to fully estimate exposure margins achieved for sofosbuvir in the rat relative to the exposure in humans at the recommended clinical dose.
Animal studies have shown a possible link to reproductive toxicity.
As a precautionary measure, sofosbuvir/velpatasvir use is not recommended during pregnancy.
It is unknown whether sofosbuvir, metabolites of sofosbuvir or velpatasvir are excreted in human milk.
Available pharmacokinetic data in animals have shown excretion of velpatasvir and metabolites of sofosbuvir in milk.
A risk to the newborns/infants cannot be excluded. Therefore, sofosbuvir/velpatasvir should not be used during breast-feeding.
No human data on the effect of sofosbuvir/velpatasvir on fertility are available. Animal studies do not indicate harmful effects of sofosbuvir or velpatasvir on fertility.
If ribavirin is co-administered with sofosbuvir/velpatasvir, refer to the Summary of Product Characterisitics for ribavirin for detailed recommendations regarding pregnancy, contraception, and breast-feeding.
Sofosbuvir/velpatasvir has no or negligible influence on the ability to drive and use machines.
The safety profile of sofosbuvir/velpatasvir has been determined in pooled Phase 3 clinical studies of patients with genotype 1, 2, 3, 4, 5 or 6 HCV infection and in the postmarketing setting. No adverse drug reactions to sofosbuvir/velpatasvir were identified from clinical studies. In the postmarketing setting, cases of severe bradycardia and heart block have been observed when SOF-containing products are used in combination with amiodarone, and HBV reactivation has been observed in patients coinfected with HCV/HBV following treatment with DAAs.
Assessment of adverse reactions for sofosbuvir/velpatasvir is based on safety data from clinical studies and postmarketing experience. All adverse reactions are presented in the following table. The adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000) or very rare (<1/10,000).
Adverse drug reactions identified with sofosbuvir/velpatasvir:
| Frequency | Adverse drug reaction |
|---|---|
| Gastrointestinal disorders | |
| Very common | vomitinga |
| Skin and subcutaneous tissue disorders | |
| Common | rashb |
| Uncommon | angioedemab |
a Adverse reaction was observed in paediatric patients aged 3 to < 6 years
b Adverse reaction identified through post-marketing surveillance for sofosbuvir/velpatasvir-containing products
Cases of severe bradycardia and heart block have been observed when sofosbuvir-containing regimens are used in combination with amiodarone and/or other medicinal products that lower heart rate.
Frequency not known: Stevens-Johnson syndrome
The adverse reactions observed were consistent with those observed in clinical studies of sofosbuvir/velpatasvir in adults. Vomiting was observed as a very common adverse drug reaction to sofosbuvir/velpatasvir in paediatric patients aged 3 to <6 years. The safety assessment of sofosbuvir/velpatasvir in paediatric patients aged 3 years and older is based on data from a Phase 2, open-label clinical study (study 1143) that enrolled 216 patients who were treated with sofosbuvir/velpatasvir for 12 weeks.
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