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.

See comments.

Recommendations

No dosage adjustment recommended.

Monitor for clinical efficacy.

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)

As clinically indicated : brivaracetam, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, rufinamide, topiramate, vigabatrin, zonisamide.

Monitor

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

Tests

Carbamazepine

Darunavir plasma level

CD4+

Viral load HIV

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.