Darunavir / ritonavir

Carbamazepine

Dose adjustment and closer monitoring may be required.

No pharmaceutical opinion available for this interaction.

Mechanism

Darunavir / ritonavir can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Carbamazepine.

Carbamazepine can induce the metabolism (CYP 3A4) and decrease the plasma concentration of Darunavir / ritonavir.

Darunavir / ritonavir

Pharmacodynamic effects

Probably without any clinical consequence.

Recommendations

No dosage adjustment recommended.

Alternative solution(s)

Carbamazepine

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

No a priori dosage adjustment is recommended.

Monitor for adverse effects.

Monitor drug levels and adjust the dose if necessary.

A decrease in dosage of 25 to 50% may be necessary.

See comments.

Alternative solution(s)

Gabapentin, pregabaline, leviracetam.

Monitor

Carbamazepine adverse effects : disorientation, ataxia, lethargy, drowsiness, nausea, vomiting, headache, diplopia, dizziness, leukopenia and hyponatremia.

Tests

Carbamazepine

Pharmacokinetic parameters
Parameters
Reference number
# patients
HIV
Dose
Frequency
AUC
Cmax
Cmin
Carbamazepine
2241
16
-
200 mg
BID
+ 45%
+ 43%
+ 54%
Darunavir / ritonavir
2241
16
-
600/100 mg
BID
- 1%
+ 4%
- 15%
Comment

Ref #2241: The active metabolite of carbamazepine has decreased: AUC and Cmax by 54% and Cmin by 52% .
The author concluded that carbamazepine may need to be reduced by 25-50% but no dose adjustment for DRV/r is recommended.

Ref #3570: TDM data were evaluated 11 HIV-positive patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months. All the TDM evaluations for carbamazepine and oxcarbazepine were within therapeutic ranges. TDM results of darunavir measured in these patients were comparable to those in the control group.

Ref #1304 : Reported case of a 20-year-old patient who developed vomiting, dizziness, elevated liver enzymes, and increased carbamazepine concentration by 87% following the addition of one dose of ritonavir 200 mg. Symptoms started within 12 hours after the first dose of ritonavir. In order to obtain a concentration within the therapeutic index, the dose of carbamazepine was reduced from 750 to 280 mg QD. Several other cases of acute toxicity to carbamazepine 2 to 4 days after the addition of ritonavir have been reported. See ritonavir + carbamazepine.

Ref #2090: Another case reported of a 50 year man who developed excessive drowsiness following the introduction of lopinavir/ritonavir and it was found that his serum carbamazepine concentration had increased by 46%. His antiretroviral therapy was then changed to nelfinavir 1250 mg BID but 3 days later the same symptoms appeared with 53% increase in carbamazepine. The symptoms of carbamazepine toxicity disappeared after a carbamazepine dose reduction of 33%. See lopinavir/ritonavir + carbamazepine.

Reference
  • 2386
    Darunavir (Prezista), Janssen, Ontario, Canada, 23 mai 2018.
  • 2241
    Sekar VJ, Tomaka F, Lavreys L et al. Pharmacokinetic interaction between darunavir in combinaison with low-dose ritonavir and carbamazepine. XVIIth International AIDS conference. Mexico 2008. Abstract TUPE0083.
  • 3570
    Cattaneo D, Baldelli S, Cozzi V, Fusi M, Atzori C, et al. Drug-Drug Interactions Between Antiretrovirals and Carbamazepine/Oxcarbazepine: A Real-Life Investigation. Ther Drug Monit. 2020 Apr; 42(2): 330-334.
  • 122
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 2988
    Carbamazepine (Tegretol), Novartis Pharma, Québec, Canada, 4 mai 2018.
  • 717
    Mateu-de Antonio J, Grau S, Gimeno-Bayon JL, Carmona A. Ritonavir-induced carbamazepine toxicity. Ann Pharmcother 2001;35:125-126.
  • 1304
    Kato Y, Fujii T, Mizoguchi N, et al. Potential interaction between ritonavir and carbamazepine. Pharmacother 2000;20(7):851-854.
  • 1312
    Garcia AB, Ibarra AL, Etessam JP, et al. Protease inhibitor-induced carbamazepine toxicity. Clin Neuropharmacol 2000;23(4):216-218.
  • 1599
    Liedtke MD, Lockhart SM, and Rathbun RC. Anticonvulsivant and antiretroviral interactions. Ann Pharmacother 2004;38:482-489.
  • 2090
    Bates D and Herman RJ. Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir. Ann Pharmacother 2006;40:1190-1195.
  • 2219
    Sandson N. An overview of Psychotropic Drug-Drug Interactions. Psychosomatics 2005;46(5) : 464-489.