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Drug Interactions between midazolam and osimertinib

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

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Interactions between your drugs

Minor

midazolam osimertinib

Applies to: midazolam and osimertinib

Coadministration with osimertinib may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. In vitro, osimertinib has been shown to be a competitive inhibitor as well as inducer of CYP450 3A4. However, a clinically significant inhibitory effect on CYP450 3A4 has not been demonstrated in clinical drug interaction studies. In a pharmacokinetic study of 49 patients with non-small cell lung cancer, coadministration of osimertinib with the sensitive CYP450 3A4 substrate simvastatin decreased the area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of simvastatin by approximately 9% and 23%, respectively. These reductions are also not considered clinically significant. Based on these observations, osimertinib may be administered with CYP450 3A4 substrates without the need for increased clinical monitoring.

References (5)
  1. (2024) "Product Information. Tagrisso (osimertinib)." Astra-Zeneca Pharmaceuticals
  2. (2024) "Product Information. Tagrisso (osimertinib)." AstraZeneca Pharma Inc
  3. (2024) "Product Information. Tagrisso (osimertinib)." AstraZeneca UK Ltd
  4. (2024) "Product Information. Tagrisso (osimertinib)." AstraZeneca Pty Ltd, 6
  5. Harvey RD, Aransay NR, Isambert N, Lee J, Arkenau T, vansteenkiste j, Dickinson PA, bui k, Weilert D, So K, thomas k, Vishwanathan K (2018) "Effect of multiple-dose osimertinib on the pharmacokinetics of simvastatin and rosuvastatin" Br J Clin Pharmacol, 84, p. 2877-88

Drug and food interactions

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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