Drug-Drug Interaction

CARBAMAZEPINE/ISONIAZID

MECHANISM OF ACTION
Isoniazid may inhibit carbamazepine metabolism.

DISCUSSION
Several case reports have documented carbamazepine toxicity as shown by ataxia, nystagmus, lethargy, and somnolence during concurrent isoniazid.(1-10) Reports have also found isoniazid-induced hepatotoxicity during concurrent therapy.(1-5)

CLINICAL EFFECTS
Concurrent use of isoniazid may result in elevated levels of and toxicity from carbamazepine and possibly isoniazid-induced hepatotoxicity.

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

PATIENT MANAGEMENT
If both drugs are administered, monitor plasma carbamazepine levels and observe the patient for signs and symptoms of carbamazepine and isoniazid toxicity. Adjust the doses of the drugs accordingly.

PREDISPOSING FACTORS
None determined.

REFERENCES

  1. Wright JM, Stokes EF, Sweeney VP. Isoniazid-induced carbamazepine toxicity .Wright JM, Stokes EF, Sweeney VP. Isoniazid-induced carbamazepine toxicity and vice versa: a double drug interaction. N Engl J Med 1982 Nov 18; 307(21):1325-7.
  2. van der Grient AJ, Kelderman CS. Fatal liver cell necrosis after .van der Grient AJ, Kelderman CS. Fatal liver cell necrosis after short-term administration of isoniazid and rifampicin to a patient already under treatment with anti-epileptic agents. Ned Tijdschr Geneeskd 1983 May 21;127(21):931.
  3. Berkowitz FE, Henderson SL, Fajman N, Schoen B, Naughton M. Acute liver .Berkowitz FE, Henderson SL, Fajman N, Schoen B, Naughton M. Acute liver failure caused by isoniazid in a child receiving carbamazepine. Int J Tuberc Lung Dis 1998 Jul;2(7):603-6.
  4. Campos-Franco J, Gonzalez-Quintela A, Alende-Sixto MR. Isoniazid-induced .Campos-Franco J, Gonzalez-Quintela A, Alende-Sixto MR. Isoniazid-induced hyperacute liver failure in a young patient receiving carbamazepine. Eur J Intern Med 2004 Oct;15(6):396-397.
  5. Barbare JC, Lallement PY, Vorhauer W, Veyssier P. Hepatotoxicity of .Barbare JC, Lallement PY, Vorhauer W, Veyssier P. Hepatotoxicity of isoniazid: influence of carbamazepine?. Gastroenterol Clin Biol 1986 Jun-Jul;10(6-7):523-4.
  6. Fleenor ME, Harden JW, Curtis G. Interaction between carbamazepine and .Fleenor ME, Harden JW, Curtis G. Interaction between carbamazepine and antituberculosis agents. Chest 1991 Jun;99(6):1554.
  7. Poo Arguelles P, Samarra Riera JM, Gairi Tahull JM, Vernet Bori A. .Poo Arguelles P, Samarra Riera JM, Gairi Tahull JM, Vernet Bori A. Carbamazepine-tuberculostatics interaction. Med Clin (Barc) 1984 Dec 15; 83(20):867-8.
  8. Garcia B, Zaborras E, Areas V, Obeso G, Jimenez I, de Juana P, Bermejo T. .Garcia B, Zaborras E, Areas V, Obeso G, Jimenez I, de Juana P, Bermejo T. Interaction between isoniazid and carbamazepine potentiated by cimetidine. Ann Pharmacother 1992 Jun;26(6):841-2.
  9. Valsalan VC, Cooper GL. Carbamazepine intoxication caused by interaction .Valsalan VC, Cooper GL. Carbamazepine intoxication caused by interaction with isoniazid. Br Med J (Clin Res Ed) 1982 Jul 24;285(6337):261-2.
  10. Block SH. Carbamazepine-isoniazid interaction. Pediatrics 1982 Apr; .Block SH. Carbamazepine-isoniazid interaction. Pediatrics 1982 Apr; 69(4):494-5.