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Drug Interaction Report

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

  • Ketalar (ketamine)
  • midazolam

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Interactions between your drugs

Major

ketamine midazolam

Applies to: Ketalar (ketamine), midazolam

MONITOR CLOSELY: Coadministration of ketamine with other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. In addition, opioid analgesics, barbiturates, and benzodiazepines may prolong the time to complete recovery from anesthesia.

MANAGEMENT: During concomitant use of ketamine with other CNS depressants, including alcohol, close monitoring of neurologic status and respiratory parameters, including respiratory rate and pulse oximetry, is recommended. Dosage adjustments should be considered according to the patient's clinical situation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Cerner Multum, Inc. "Australian Product Information." O 0
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. "Product Information. Ketalar (ketamine)." JHP Pharmaceuticals, Saddle River, NJ.

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Drug and food interactions

Moderate

ketamine food

Applies to: Ketalar (ketamine)

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

GENERALLY AVOID: Coadministration of oral ketamine with grapefruit juice may significantly increase the plasma concentrations of S(+) ketamine, the dextrorotatory enantiomer of ketamine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. When a single 0.2 mg/kg dose of S(+) ketamine was administered orally on study day 5 with grapefruit juice (200 mL three times daily for 5 days) in 12 healthy volunteers, mean S(+) ketamine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.1- and 3.0-fold, respectively, compared to administration with water. In addition, the elimination half-life of S(+) ketamine increased by 24% with grapefruit juice, and the ratio of the main metabolite norketamine to ketamine was decreased by 57%. The pharmacodynamics of ketamine were also altered by grapefruit juice. Specifically, self-rated relaxation was decreased and performance in the digit symbol substitution test was increased with grapefruit juice, but other behavioral or analgesic effects were not affected.

MANAGEMENT: Patients receiving ketamine should not drink alcohol. Caution is advised when ketamine is used in patients with acute alcohol intoxication or a history of chronic alcoholism. Following anesthesia with ketamine, patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination, such as driving or operating hazardous machinery, for at least 24 hours and until they know how the medication affects them. Patients treated with oral ketamine should also avoid consumption of grapefruit and grapefruit juice during treatment. Otherwise, dosage reductions of oral ketamine should be considered.

References

  1. Peltoniemi MA, Saari TI, Hagelberg NM, Laine K, Neuvonen PJ, Olkkola KT "S-ketamine concentrations are greatly increased by grapefruit juice." Eur J Clin Pharmacol 68 (2012): 979-86
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. "Product Information. Ketalar (ketamine)." JHP Pharmaceuticals, Saddle River, NJ.
View all 4 references

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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

  1. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther 58 (1995): 20-8
  2. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  4. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn, Kalamazoo, MI.
  5. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn, Kalamazoo, MI.
  6. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  7. "Product Information. Valium (diazepam)." Roche Laboratories, Nutley, NJ.
View all 7 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.

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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