Liverpool HEP Interactions

Potential Interaction

Sofosbuvir/Velpatasvir

Oxcarbazepine

Summary:

Coadministration has not been formally studied and is not currently recommended. Concentrations of velpatasvir and sofosbuvir may decrease due to induction of P-gp and/or CYPs 2B6, 2C8 and 3A4 by oxcarbazepine; this may lead to reduced therapeutic effect and potential virological failure. Note - there are a small number of cases reported of patients who have remained on an inducing antiepileptic during HCV DAA therapy (including with sofosbuvir/velpatasvir) and achieved a sustained virologic response. Although every effort to prevent concomitant use of sofosbuvir/velpatasvir and inducers should be made, these cases have demonstrated that clinical cure may still be achieved in patients where coadministration cannot be avoided. Therapeutic drug level monitoring could be considered, where available.

Description:

Interaction not studied. Medicinal products that are moderate P-gp or moderate CYP inducers (e.g. oxcarbazepine) may decrease sofosbuvir or velpatasvir plasma concentrations leading to reduced therapeutic effect of Epclusa. Co-administration of such medicinal products with Epclusa is not recommended.

Epclusa Summary of Product Characteristics, Gilead Sciences Ltd., March 2021.

Five patients on inducing antiepileptic agents (including oxcarbazepine, phenytoin and eslicarbazepine) initiated standard doses of DAA therapy with glecaprevir/pibrentasvir for 8 weeks (n=2), sofosbuvir/velpatasvir for 12 weeks (n=2) and ledipasvir/sofosbuvir for 12 weeks (n=1). Plasma DAA levels were not analysed. All patients achieved SVR12 and no adverse events or dose modifications were reported.

Anti-epileptic drugs and hepatitis C therapy: Real-world experience. Marcos-Fosch C, Cabezas J, Crespo J et al., J Hepatol, 2021, 75(4): 984-5.

A retrospective case series of 5 patients on inducing antiepileptic agents (including carbamazepine, phenytoin, and phenobarbital) initiated standard doses of DAA therapy with glecaprevir/pibrentasvir for 8 weeks (n=4) and ledipasvir/sofosbuvir for 12 weeks (n=1). Plasma DAA levels were not analysed. All patients achieved SVR12 and no adverse events or dose modifications were reported.

When coadministration cannot be avoided: real world experience of direct acting antivirals for the treatment of hepatitis C virus infection in patients on first generation anticonvulsants. Natali KM, Jimenez HR, & Slim J. J Pharm Pract 2022, 35(3):495-499.

A case was reported of a 42-year-old female patient with HCV infection and severe bilateral trigeminal neuralgia and multiple sclerosis. Her pain was treated with oxcarbazepine 900 mg, three times daily. Other treatments for her pain had been unsuccessful. Her HCV was treated with sofosbuvir/velpatasvir for 12 weeks, with the addition of ketoconazole 400 mg daily as a pharmacokinetic booster. Four doses of sofosbuvir/velpatasvir were missed due to complications with her trigeminal neuralgia, but she achieved SVR12.

Successful treatment of hepatitis C virus infection in patients on anti-epileptics or mood stabilizers using pharmacokinetic enhancers. J Yin, L Hill, M Mansour et al. Br J Clin Pharmacol, 2023, Online ahead of print

Coadministration of DAAs and enzyme-inducing anti-epileptic drugs was studied in a retroactive case series across six centres in the UK. Eleven patients with chronic treatment-naïve HCV infection were treated with standard courses of DAAs (12 weeks of sofosbuvir/velpatasvir; n=6, 8 weeks ledipasvir/sofosbuvir; n=3, 8 weeks glecaprevir/pibrentasvir; n=2). Coadministered enzyme inducing anti-epileptics included carbamazepine (n=6), phenytoin (n=3), oxcarbazepine (n=1), and phenobarbitone (n=1). SVR results were available for 9 patients (82%), with no virological failures, including one patient who completed 50% of the DAA course. Of the 2 patients that did not attend for SVR bloods, 1 had an end of treatment response. These results should help inform treatment decisions in patients taking enzyme-inducing anti-epileptic drugs.

Coadministration of hepatitis C direct-acting antivirals and enzyme-inducing antiepileptic drugs: real-world experience from a multi-centre case series. Boyle A, Marra F, Boothman H et al. Journal of Hepatology, 2023; 78(S1): S1202.

View all available interactions with Sofosbuvir/Velpatasvir by clicking here.