https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=13542
https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=13542
Document made available to the pharmacist to communicate a drug interaction to the doctor.
DOWNLOADPhenobarbital may induce P-gp and decrease the plasma concentration of Ledipasvir / Sofosbuvir.
Possible decrease of clinical efficacy.
Avoid this association. Use with caution if it can not be avoided.
Closely monitor clinical effectiveness.
See comments for further details.
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Choose an alternative if possible.
Gabapentin, pregabalin, valproic acid, clobazam, leviracetam, topiramate, lacosamide or lamotrigine.
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TDM levels of DAAs
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The product monograph does not recommend co-administration with strong P-gp inducers. 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 #3524 : In this retrospective case series of five patients on first generation anticonvulsants (carbamazepine, phenobarbital, phenytoin), four were treated with glecaprevir/pibrentasvir for 8 weeks and one with ledipasvir/sofosbuvir for 12 weeks. All five patients achieved SVR despite this drug interaction. The authors conclude that all efforts to prevent concomitant use with strong inducers should be made.
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.