Coadministration of carbamazepine (300 mg, twice daily) with sofosbuvir (400 mg, single dose) decreased sofosbuvir both Cmax and AUC by 48%. GS-331007 Cmax increased by 4% while AUC decreased by 1%. Drugs that are inducers of P-gp and/or moderate to potent inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g., carbamazepine) may significantly decrease plasma concentrations of velpatasvir, leading to potentially reduced therapeutic effect of sofosbuvir/velpatasvir. The use of these agents with sofosbuvir/velpatasvir is not recommended.

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.

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.

A case was reported of a 50-year-old man with HCV infection and epilepsy, stabilized on carbamazepine 400 mg twice daily, lacosamide 200 mg daily, and zonisamide 300 mg daily. On the last occasion his physician had attempted to switch from carbamazepine, he had experienced a seizure. He was initiated on sofosbuvir/velpatasvir for 12 weeks, and given ketoconazole 200 mg daily as a pharmacokinetic booster. Two doses of sofosbuvir/velpatasvir and three doses of ketoconazole were missed, resulting in a high viral load in week 4, however, by week 6 his viral load was undetectable and he achieved SVR12. His epilepsy was stable, with no seizures.

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.