Drug-Drug Interaction

CARBAMAZEPINE; OXCARBAZEPINE/MONOAMINE OXIDASE INHIBITORS

MECHANISM OF ACTION
Carbamazepine and oxcarbazepine are structurally related to the tricyclic antidepressants, which may sensitize adrenergic receptors to amines that can accumulate extra neuronally as a result of MAO inhibition.

DISCUSSION
Carbamazepine's chemical structure is similar to that of the tricyclic antidepressants (TCAs).(1,2) TCA serum levels have been elevated by coadministration of isoniazid, a monoamine oxidase inhibitor. Because of these similarities, it has been hypothesized that MAOIs could inhibit the metabolism of carbamazepine.(1,4)

CLINICAL EFFECTS
Concurrent use of carbamazepine or oxcarbazepine with a MAOI may result in serotonin syndrome.

SEVERITY LEVEL
1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

PATIENT MANAGEMENT
The US manufacturer of carbamazepine states that MAOIs should be discontinued at least 14 days prior to initiation of carbamazepine therapy.(2)

PREDISPOSING FACTORS
None determined.

REFERENCES

  1. Ketter TA, Post RM, Parekh PI, Worthington K. Addition of monoamine .Ketter TA, Post RM, Parekh PI, Worthington K. Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression. J Clin Psychiatry 1995 Oct;56(10):471-5.
  2. Tegretol (carbamazepine) US prescribing information. Novartis .Tegretol (carbamazepine) US prescribing information. Novartis Pharmaceuticals Corporation December, 2007.
  3. Parnate (tranylcypromine sulfate) US prescribing information. .Parnate (tranylcypromine sulfate) US prescribing information. GlaxoSmithKline June, 2007.
  4. Barklage NE, Jefferson JW, Margolis D. Do monoamine oxidase inhibitors .Barklage NE, Jefferson JW, Margolis D. Do monoamine oxidase inhibitors alter carbamazepine blood levels?. J Clin Psychiatry 1992 Jul;53(7):258.
  5. Lydiard RB, White D, Harvey B, Taylor A. Lack of pharmacokinetic .Lydiard RB, White D, Harvey B, Taylor A. Lack of pharmacokinetic interaction between tranylcypromine and carbamazepine. J Clin Psychopharmacol 1987 Oct;7(5):360.
  6. Joffe RT, Post RM, Uhde TW. Lack of pharmacokinetic interaction of .Joffe RT, Post RM, Uhde TW. Lack of pharmacokinetic interaction of carbamazepine with tranylcypromine. Arch Gen Psychiatry 1985 Jul; 42(7):738.
  7. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir .Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John's wort. Lancet 2000 Feb 12;355(9203):547-8.
  8. Anonymous. From the Food and Drug Administration. JAMA 2000 Apr 5; .Anonymous. From the Food and Drug Administration. JAMA 2000 Apr 5; 283(13):1679.