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Drug Interactions between nefazodone and triazolam

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

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Interactions between your drugs

Major

triazolam nefazodone

Applies to: triazolam and nefazodone

CONTRAINDICATED: Coadministration with nefazodone may significantly increase the plasma concentrations of triazolam. The mechanism is nefazodone inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of triazolam. In healthy male volunteers, administration of triazolam (0.25 mg) with nefazodone (200 mg orally twice a day for 7 days) resulted in a 1.7-fold increase in mean triazolam peak plasma concentration (Cmax), a 3-fold increase in half-life, and a nearly 4-fold increase in systemic exposure (AUC) compared to administration without nefazodone. These changes were associated with increased sedation and impaired psychomotor performance. Triazolam did not affect the pharmacokinetics of nefazodone.

MANAGEMENT: A 75% reduction in the initial dosage of triazolam has been recommended when prescribed with nefazodone. However, because such a small dose is not generally achievable with commercially available formulations of triazolam, coadministration with nefazodone is considered contraindicated. Lorazepam, oxazepam, and temazepam are not metabolized by CYP450 3A4 and may be suitable alternatives in patients requiring nefazodone and a benzodiazepine.

References (7)
  1. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  2. (2001) "Product Information. Serzone (nefazodone)." Bristol-Myers Squibb
  3. Kroboth PD, Mcauley JW, Derry CL (1995) "Time-dependent sensitization to triazolam? An observation in three studies." J Clin Psychopharmacol, 15, p. 192-6
  4. Kroboth PD, Folan MM, Lush RM, Chaikin PC, Shukla UA, Barbhaiya R, Salazar DE (1995) "Coadministration of nefazodone and benzodiazepines: 1. pharmacodynamic assessment." J Clin Psychopharmacol, 15, p. 306-19
  5. Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS (1995) "Coadministration of nefazodone and benzodiazepines: 2. a pharmacokinetic interaction study with triazolam." J Clin Psychopharmacol, 15, p. 320-6
  6. Riesenman C (1995) "Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal." Pharmacotherapy, 15, s84-99
  7. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57

Drug and food interactions

Moderate

triazolam food

Applies to: triazolam

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References (7)
  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. 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
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 (4)
  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

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

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