Glecaprevir / Pibrentasvir

Carbamazepine

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

Carbamazepine may induce CYP 3A4 and P-gp and decrease the plasma concentration of Glecaprevir / Pibrentasvir.

Glecaprevir / Pibrentasvir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Recommendations

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

Closely monitor clinical effectiveness.

See comments.

Alternative solution(s)

Carbamazepine

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
Parameters
Reference number
# patients
HCV
Dose
Frequency
AUC
Cmax
Glecaprevir / Pibrentasvir
3709
10
-
300/120 mg
x 1
- 66%/- 51%
- 67%/- 50%
Carbamazepine
3709
10
-
200 mg
BID
+ 2%
- 4%
Comment

The product monograph does not recommend co-administration with strong P-gp and CYP 3A4 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.

Reference
  • 3373
    Glecaprevir/Pibrentasvir (Maviret), Abbvie, Québec, Canada, 30 octobre 2020.
  • 3709
    Kosloski MP, Li H, Wang S, Mensa F, Kort J et al. Characterizing complex and competing drug-drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine. Clin Transl Sci . 2023 Apr; 16(4): 593-605.
  • 3524
    Natali KM, Jimenez HR, and J Slim. 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. Journal of Pharmacy Practice. 2022, 35(3): 495-499.
  • 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.