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Drug Interactions between disulfiram and midazolam

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

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Interactions between your drugs

Moderate

midazolam disulfiram

Applies to: midazolam and disulfiram

ADJUST DOSE: The combination of disulfiram and benzodiazepines may increase CNS depression. The mechanism may relate to the inhibition of hepatic oxidation of benzodiazepines by disulfiram. Diazepam and chlordiazepoxide may interact with disulfiram to a greater extent than other benzodiazepines. However, the interaction has also been reported with temazepam, even though it is metabolized by glucuronidation.

MANAGEMENT: The benzodiazepine dosage may require reduction. Patients should be monitored for excessive and prolonged sedation.

References (3)
  1. MacLeod SM, Sellers EM, Giles HG, et al. (1978) "Interaction of disulfiram with benzodiazepines." Clin Pharmacol Ther, 24, p. 583-9
  2. Sellers EM, Giles HG, Greenblatt DJ, Naranjo CA (1980) "Differential effects on benzodiazepine disposition by disulfiram and ethanol." Arzneimittelforschung, 30, p. 882-6
  3. Hardman M, Biniwale A, Clarke CE (1994) "Temazepam toxicity precipitated by disulfiram." Lancet, 344, p. 1231-2

Drug and food interactions

Major

disulfiram food

Applies to: disulfiram

CONTRAINDICATED: Consumption of ethanol during treatment with disulfiram may cause flushing, nausea, blurred vision, dyspnea, tachypnea, tachycardia, and hypotension. Death has been reported. The mechanism is probably related to inhibition of aldehyde dehydrogenase, the enzyme responsible for the oxidation of acetaldehyde to acetyl CoA. Accumulation of acetaldehyde probably results.

MANAGEMENT: Ethanol should be avoided in patients receiving disulfiram.

References (3)
  1. Jones RO (1949) "Death following the ingestion of alcohol in an antabuse treated patient." Can Med Assoc J, 60, p. 609-12
  2. Stoll D, King LE (1980) "Disulfiram-alcohol skin reaction to beer-containing shampoo." JAMA, 244, p. 2045
  3. van Ieperen L (1984) "Sudden death during disulfiram-ethanol reaction." S Afr Med J, 66, p. 165
Moderate

midazolam food

Applies to: midazolam

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

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.

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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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