Liverpool HEP Interactions

Potential Interaction

Ledipasvir/Sofosbuvir

Oxcarbazepine

Summary:

Coadministration with ledipasvir/sofosbuvir has not been formally studied and is not currently recommended. Induction of P-gp by oxcarbazepine may significantly decrease plasma concentrations of ledipasvir and sofosbuvir; 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 ledipasvir/sofosbuvir) and achieved a sustained virologic response. Although every effort to prevent concomitant use of ledipasvir/sofosbuvir 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:

Medicinal products that are moderate P-gp inducers in the intestine (e.g. oxcarbazepine) may decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of ledipasvir/sofosbuvir. Co-administration of such medicinal products is not recommended with ledipasvir/sofosbuvir. This interaction has not been studied but is expected to decrease exposure of ledipasvir and sofosbuvir due to induction of P-gp leading to reduced therapeutic effect of ledipasvir/sofosbuvir. GS-331007 is not expected to be affected.

Harvoni Summary of Product Characteristics, Gilead Sciences Ltd, January 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.

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 Ledipasvir/Sofosbuvir by clicking here.