Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study

Ther Drug Monit. 2024 Jun 1;46(3):277-280. doi: 10.1097/FTD.0000000000001179. Epub 2024 Apr 26.

Abstract

Background: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations.

Methods: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia.

Results: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses.

Conclusions: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Publication types

  • Case Reports

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use
  • Carbamazepine* / pharmacokinetics
  • Carbamazepine* / therapeutic use
  • Darunavir* / pharmacokinetics
  • Darunavir* / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Interactions*
  • Drug Monitoring / methods
  • HIV Infections* / drug therapy
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Oxazines / pharmacokinetics
  • Oxazines / therapeutic use
  • Piperazines / pharmacokinetics
  • Piperazines / therapeutic use
  • Pyridones / blood
  • Pyridones / pharmacokinetics
  • Pyridones / therapeutic use
  • Ritonavir / administration & dosage
  • Ritonavir / therapeutic use
  • Trigeminal Neuralgia / drug therapy

Substances

  • Darunavir
  • Carbamazepine
  • Ritonavir
  • Anticonvulsants
  • dolutegravir
  • Pyridones
  • Heterocyclic Compounds, 3-Ring
  • Piperazines
  • Oxazines
  • Anti-HIV Agents