Sofosbuvir / Velpatasvir

Oxcarbazepine

Not recommended association.

Available pharmaceutical opinion

Document made available to the pharmacist to communicate a drug interaction to the doctor.

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Mechanism

Oxcarbazepine may induce CYP 3A4 and P-gp and decrease the plasma concentration of Sofosbuvir / Velpatasvir.

Sofosbuvir / Velpatasvir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Recommendations

Do not administer with potent P-gp inducers or with moderate to potent CYP2B6, 2C8 or 3A4 inducers.

Avoid this association. Use with caution if it can not be avoided.

Closely monitor clinical effectiveness.

See comments.

Alternative solution(s)

Oxcarbazepine

Pharmacodynamic effects

Recommendations

Choose an alternative if possible.

Alternative solution(s)

Gabapentin, pregabalin, levetiracetam, brivaracetam, or valproic acid

Monitor

Tests

TDM levels of DAAs

Pharmacokinetic parameters

Comment

The product monograph does not recommend co-administration with strong P-gp or moderate to strong inducers of CYP2B6, 2C8 or 3A4. However, a small number of cases have been reported in patients who remained on inducer AEDs during direct-acting antiviral (DAA) therapy for HCV and achieved a sustained virologic response (SVR). These cases appear to demonstrate that clinical cure can still be achieved in patients for whom co-administration cannot be avoided.

Case reports of patients who received standard doses of DDAs against HCV while being maintained on an inducing antiepileptic.

Ref #3710 : Another case report of five patients on anticonvulsant inducers (oxcarbazepine, phenytoin and eslicarbazepine) who started treatment with glecaprevir/pibrentasvir for 8 weeks (n=2), sofosbuvir/velpatasvir for 12 weeks (n=2) or ledipasvir/ sofosbuvir for 12 weeks (n=2). All five patients achieved SVR at 12 weeks. DAAs levels were not measured.

Ref #3711 : Another retrospective case series from six UK centers presents eleven patients on anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) and treated with standard DAA therapy (sofosbuvir/velpatasvir; n=6, ledipasvir /sofosbuvir; n=3, glecaprevir/pibrentasvir; n=2). RSV results were available for 9 patients (82%) with no virological failure and including one patient who had only completed 50% of his treatment.

Reference
  • 3250
    Sofosbuvir/Velpatasvir (Epclusa), Gilead Sciences, Ontario, Canada, 5 novembre 2020.
  • 3710
    Marcos-Fosch C, Cabezas J, Crespo J and M Buti. Anti-epileptic drugs and hepatitis C therapy: Real-world experience. J Hepatol, 2021, 75(4): 984-5.
  • 3711
    Boyle A, Marra F, Boothman H et al. Coadministration of hepatitis C direct-acting antivirals and enzyme-inducing antiepileptic drugs: real-world experience from a multi-centre case series. Journal of Hepatology, 2023; 78(S1): S1202.