https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=13344

Darunavir / cobicistat

Carbamazepine

Contraindicated.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Darunavir / cobicistat may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Carbamazepine.

Darunavir / cobicistat

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Risk of a possible development of resistance to antiretroviral class.

Recommendations

Monitor for signs and symptoms of therapeutic failure.

Alternative solution(s)

–

Carbamazepine

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Contraindicated. Use alternative.

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

Darunavir plasma level

CD4+

Viral load HIV

Carbamazepine

Pharmacokinetic parameters

–

Comment

See carbamazepine + elvitegravir/cobicistat.

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
  • 3071
    Darunavir/cobicistat (Prezcobix), Janssen, Ontario, Canada, 7 avril 2017.
  • 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.
  • 3437
    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza), Janssen Inc, Ontario, Canada, 3 octobre 2018.