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Drug Interactions between carbamazepine and nefazodone

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

carBAMazepine nefazodone

Applies to: carbamazepine and nefazodone

CONTRAINDICATED: Coadministration of carbamazepine and nefazodone may result in significantly decreased plasma concentrations of nefazodone and its active metabolite, hydroxynefazodone, and increased plasma concentrations of carbamazepine. The proposed mechanism is carbamazepine induction of nefazodone and hydroxynefazodone metabolism via CYP450 3A4, and nefazodone inhibition of carbamazepine metabolism via the same isoenzyme. In 12 healthy subjects administered carbamazepine 200 mg twice daily with nefazodone 200 mg twice daily to steady state, an approximately 85% reduction in peak plasma concentration (Cmax) and nearly 95% reduction in systemic exposure (AUC) were reported for both nefazodone and hydroxynefazodone, which would likely lead to therapeutic failure in a clinical setting. Carbamazepine Cmax and AUC were increased by 23%. Case reports have described carbamazepine toxicity following the initiation of nefazodone therapy, necessitating a reduction in carbamazepine dosage or discontinuation of nefazodone.

MANAGEMENT: Concomitant use of nefazodone and carbamazepine is considered contraindicated.

References

  1. (2001) "Product Information. Serzone (nefazodone)." Bristol-Myers Squibb
  2. Nemeroff CB, Devane CL, Pollock BG (1996) "Newer antidepressants and the cytochrome p450 system." Am J Psychiatry, 153, p. 311-20
  3. Ashton AK, Wolin RE (1996) "Nefazodone-induced carbamazepine toxicity." Am J Psychiatry, 153, p. 733
  4. Yong JN (1997) "Nefazodone and neurotoxicity." J Clin Psychiatry, 58, p. 365
  5. Laroudie C, Salazar DE, Cosson JP, Cheuvart B, Istin B, Girault J, Ingrand I, Decourt JP (2000) "Carbamazepine-nefazodone interaction in healthy subjects." J Clin Psychopharmacol, 20, p. 46-53
  6. Roth L, Bertschy G (2001) "Nefazodone may inhibit the metabolism of carbamazepine: three case reports." Eur Psychiatry, 16, p. 320-1
View all 6 references

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: carbamazepine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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Moderate

nefazodone food

Applies to: nefazodone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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