Mitotane with Midazolam Interaction Details
Brand Names Associated with Mitotane
- Lysodren®
- Mitotane
Brand Names Associated with Midazolam
- Midazolam
- Versed®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 29, 2023
Interaction Effect
Decreased midazolam exposure
Interaction Summary
Coadministration of mitotane, a hepatic enzyme inducer, and midazolam, a CYP3A4 substrate , has resulted in reduced midazolam exposure in a pharmacokinetic study (n=11) . Caution should be used when using mitotane with drugs susceptible to hepatic enzyme induction . Monitor patient response to midazolam therapy and make dosage adjustments as necessary to maintain efficacy .
Severity
Moderate
Onset
Rapid
Evidence
Established
How To Manage Interaction
Caution should be used when using mitotane with drugs susceptible to hepatic enzyme induction, such as midazolam . Coadministration of mitotane and oral midazolam may result in decreased midazolam exposure . Monitor patient response to midazolam therapy and make dosage adjustments as necessary to maintain efficacy .
Mechanism Of Interaction
Induction of CYP3A4-mediated midazolam metabolism
Literature Reports
A) Midazolam exposure was markedly reduced when midazolam and mitotane were coadministered in an uncontrolled pharmacokinetic study (n=11). Four patients were on mitotane with doses ranging from 0.5 g/day alternating with 1 g/day to 10.5 g/day; 2 of these patients were also on sunitinib. The mitotane concentrations in these 4 patients ranged from 4.9 to 17.8 mg/L. Another 7 patients received multiple-doses of sunitinib 37.5 to 50 mg/day alone. After administration of a single-dose of midazolam 7.5 mg orally in all 11 patients, the mean AUC for midazolam and 1-OH midazolam was 7.6 microgram x hr/L (95% confidence interval (CI), 5.5 to 9.7 microgram x hr/L) and 409.6 microgram x hr/L (95% CI, 290.5 to 528.7 microgram x hr/L), respectively, when administered to patients on mitotane (n=4) compared with 139 microgram x hr/L (95% CI, 95.1 to 182.9 microgram x hr/L) and 35 microgram x hr/L (95% CI, 26.4 to 43.6 microgram x hr/L), respectively, when administered to patients on sunitinib alone (n=7) .
Mitotane Overview
-
Mitotane is used to treat cancer of the adrenal gland that can not be treated with surgery. Mitotane is in a class of medications called antineoplastic agents. It works by slowing growth or reducing the size of the tumor.
Midazolam Overview
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Midazolam is given to children before medical procedures or before anesthesia for surgery to cause drowsiness, relieve anxiety, and prevent any memory of the event. Midazolam is in a class of medications called benzodiazepines. It works by slowing activity in the brain to allow relaxation and sleep.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.