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)

Gabapentin, pregabaline, leviracetam.

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.