Clinical cure may still be achieved by patients with chronic hepatitis C virus (HCV) receiving direct acting antivirals (DAAs) and first generation anticonvulsants, according to a recent retrospective case series published in the Journal of Pharmacy Practice.

While DAAs have significantly improved the treatment of chronic HCV infection by eliciting higher rates of sustained virologic response (SVR) compared to other therapies, they also interact with a number of agents that could potentially limit their effectiveness and cause treatment resistance. In this case series, the authors focused on analyzing the interaction between first generation anticonvulsants (ie, phenytoin, carbamazepine, phenobarbital), which are potent inducers of CYP450 isoenzymes and drug transporters, and DAAs. Although the current recommendation is to avoid concomitant use of these agents, evidence surrounding this interaction is limited, leaving providers inadequate guidance on how to manage patients requiring both therapies.

In this retrospective report, 5 cases of patients with chronic HCV infection who successfully achieved clinical cure using standard doses of DAAs while receiving anticonvulsants with induction properties were presented. Clinical cure was defined as SVR 12 weeks after completing DAA therapy.

The authors reported that 80% of the patients had HCV genotype 1a and 20% had genotype 1b; 4 patients received glecaprevir/pibrentasvir for 8 weeks, while 1 patient received ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant therapy consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. The authors reported that SVR was achieved by all 5 patients despite the drug-drug interaction.


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“Postponing or avoiding HCV treatment based on a potential interaction without providing a solution is leading to progression of liver disease in this patient population,” the authors stated. They added, “Treating HCV infection with standard dose DAAs in patients maintained on first generation anticonvulsants requires careful consideration and a thorough, patient-specific evaluation of risk versus benefit.”

The authors concluded that additional studies should be conducted in order to better understand this interaction as well as provide more definitive guidance to practitioners met with this challenge.

Disclosure: Multiple authors declared conflicts of interest. Please refer to the original article for a full list of disclosures.

Reference

1.      Natali KM, Jimenez HR, Slim J. 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. J. Pharm. Pract. 2020. doi: 10.1177/0897190020977762.