Drug-Drug Interaction

CARBAMAZEPINE/PROTEASE INHIBITORS

MECHANISM OF ACTION
Carbamazepine may induce the metabolism of the protease inhibitors at CYP P-450-3A4.(1-7) Ritonavir may inhibit the metabolism of carbamazepine by CYP P-450-3A4.(8,9)

DISCUSSION
In a study in 16 subjects, concurrent carbamazepine (200 mg twice daily) with darunavir/ritonavir (600/100 mg twice daily) had no significant effects on darunavir pharmacokinetics. The maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of carbamazepine increased by 43%, 45%, and 54%, respectively. The Cmax, AUC, and Cmin of carbamazepine epoxide decreased by 54%, 54%, and 52%, respectively.(10)

CLINICAL EFFECTS
The concurrent use of indinavir and carbamazepine may result in higher than anticipated carbamazepine levels, decreased indinavir plasma levels, and antiretroviral therapy failure.(1,2)

SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

PATIENT MANAGEMENT
Consider avoiding the concurrent use of carbamazepine and amprenavir, fosamprenavir, indinavir, lopinavir nelfinavir, or saquinavir. If concurrent therapy is warranted, carbamazepine and protease inhibitor levels, as well as antiretroviral response, should be closely monitored.

PREDISPOSING FACTORS
None determined.

REFERENCES

  1. Crixivan (indinavir sulfate) US prescribing information. Merck & Co., Inc. .Crixivan (indinavir sulfate) US prescribing information. Merck & Co., Inc. April, 2010.
  2. Hugen PW, Burger DM, Brinkman K, ter Hofstede HJ, Schuurman R, Koopmans .Hugen PW, Burger DM, Brinkman K, ter Hofstede HJ, Schuurman R, Koopmans PP, Hekster YA. Carbamazepine--indinavir interaction causes antiretroviral therapy failure. Ann Pharmacother 2000 Apr;34(4):465-70.
  3. Agenerase (amprenavir) Oral Solution US prescribing information. .Agenerase (amprenavir) Oral Solution US prescribing information. GlaxoSmithKline May, 2005.
  4. Lexiva (fosamprenavir calcium) US prescribing information. GlaxoSmithKline .Lexiva (fosamprenavir calcium) US prescribing information. GlaxoSmithKline April, 2010.
  5. Kaletra (lopinavir/ritonavir tablets) US prescribing information. Abbott .Kaletra (lopinavir/ritonavir tablets) US prescribing information. Abbott Laboratories April, 2010.
  6. Viracept (nelfinavir mesylate) US prescribing information. Agouron .Viracept (nelfinavir mesylate) US prescribing information. Agouron Pharmaceuticals, Inc. April, 2010.
  7. Invirase (saquinavir mesylate) US prescribing information. Roche .Invirase (saquinavir mesylate) US prescribing information. Roche Laboratories, Inc. April, 2010.
  8. Norvir (ritonavir) US prescribing information. Abbott Laboratories April, .Norvir (ritonavir) US prescribing information. Abbott Laboratories April, 2010.
  9. Berbel Garcia A, Latorre Ibarra A, Porta Etessam J, Martinez Salio A, .Berbel Garcia A, Latorre Ibarra A, Porta Etessam J, Martinez Salio A, Perez Martinez D, Siaz Diaz R, Toledo Heras M. Protease inhibitor-induced carbamazepine toxicity. Clin Neuropharmacol 2000 Jul-Aug;23(4):216-8.
  10. Prezista (darunavir) US prescribing information. Tibotec Inc. April, .Prezista (darunavir) US prescribing information. Tibotec Inc. April, 2010.
  11. Kato Y, Fujii T, Mizoguchi N, Takata N, Ueda K, Feldman MD, Kayser SR. .Kato Y, Fujii T, Mizoguchi N, Takata N, Ueda K, Feldman MD, Kayser SR. Potential interaction between ritonavir and carbamazepine. Pharmacotherapy 2000 Jul;20(7):851-4.