Liverpool HEP Interactions

Potential Interaction

Sofosbuvir

Primidone

Summary:

Coadministration is not currently recommended. Phenobarbital, a major metabolite of primidone, is a potent inducer of P-gp and may significantly decrease sofosbuvir concentrations. This may result in loss of efficacy 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) and achieved a sustained virologic response. Although every effort to prevent concomitant use of sofosbuvir and potent 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:

Six patients on inducing antiepileptic agents (including carbamazepine, phenytoin, and phenobarbital) initiated DAA therapy with sofosbuvir 400 mg QD and daclatasvir 60 mg BID (n=2) or 60 mg TID (n=4) for 12 -24 weeks, guided by therapeutic drug level monitoring. One patient initially received DAC 60 mg BID but, due to low daclatasvir exposure, the dose was increased to 60 mg TID. SVR 12 was achieved in all patients with no serious adverse events reported. Despite the increased dose of daclatasvir, exposure of daclatasvir was 69% lower when compared with reference values of HCV-infected patients without cirrhosis on 60 mg QD. No reduction in sofosbuvir exposure in patients on carbamazepine 400 mg/day and phenobarbital 100 mg/day was observed. However, a 3-fold lower sofosbuvir exposure was observed for carbamazepine ≥1,000 mg/day compared with reference values (no dose adjustment was made). For 2 patients, sofosbuvir data were not evaluable.

Successful HCV treatment of patients on contraindicated anti-epileptic drugs: Role of drug level monitoring. van Seyen M, Smolders EJ, van Wijngaarden P et al., J Hep, 2019, 70:548-77.

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.

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