Liverpool HIV Interactions

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Potential Interaction

Dolutegravir (DTG)

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by oxcarbazepine. Interaction studies with dolutegravir and rifampicin (a strong inducer) showed that the effect of induction on dolutegravir concentrations can be overcome by administering an additional 50 mg dose of dolutegravir. The US Prescribing Information for dolutegravir advises to avoid coadministration with oxcarbazepine due to insufficient data to make dosing recommendations. However, the European SPC recommends that dolutegravir be dosed at 50 mg twice daily, but that alternative combinations should be used where possible in INSTI-resistant patients. This dose adjustment should be maintained for approximately 2 weeks after stopping oxcarbazepine as the inducing effect may persist after discontinuation of a strong inducer. Limited data from a small number of patients showed TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges and trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs.

Description:

Coadministration with oxcarbazepine, phenytoin or phenobarbital has not been studied but is expected to decreased dolutegravir exposure due to induction of UGT1A1 and CYP3A. A similar reduction in exposure as observed with carbamazepine is expected (AUC, Cmax and Ctrough decreased by 49%, 33% and 73%). The recommended adult dose of dolutegravir is 50 mg twice daily when co-administered with these metabolic inducers. In paediatric patients the weight-based once daily dose should be administered twice daily. Alternative combinations that do not include these metabolic inducers should be used where possible in INI-resistant patients.

Tivicay Summary of Product Characteristics, ViiV Healthcare, March 2019.

Coadministration may decrease dolutegravir concentrations. Avoid coadministration with dolutegravir because there are insufficient data to make dosing recommendations.

Tivicay US Prescribing Information, ViiV Healthcare, July 2019.

The drug-drug interactions between antiretrovirals and carbamazepine or oxcarbazepine were evaluated in a clinical setting using therapeutic drug monitoring (TDM) trough concentrations collected from HIV+ patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. Eleven HIV-positive patients prescribed carbamazepine (n=7) or oxcarbazepine (n=4) were identified. All the TDM evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges. Trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs (191 ± 78 versus 1096 ± 510 ng/mL). Co-administration of carbamazepine or oxcarbazepine with dolutegravir should be avoided owing to the potential risk of virological failure; the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.

Drug-drug interactions between antiretrovirals and carbamazepine/oxcarbazepine: a real-life investigation. Cattaneo D, Baldelli S, Cozzi V, et al. Ther Drug Monit. 2020;42(2):330-334.