Warfarin with Mitotane Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Mitotane
- Lysodren®
- Mitotane
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 29, 2023
Interaction Effect
Decreased warfarin effectiveness
Interaction Summary
Concomitant administration of mitotane and warfarin may result in decreased warfarin exposure. Concurrent administration of warfarin and mitotane has been reported to result in a reduction in the hypoprothrombinemic effects of warfarin, necessitating increased warfarin doses to maintain therapeutic prothrombin times . If coadministration is clinically necessary, monitor patients for changes in dosing requirements . It is speculated that the mitotane, being related to organochlorine insecticides, may have accelerated warfarin metabolism secondary to microsomal enzyme induction.
Severity
Moderate
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant administration of mitotane and warfarin may result in decreased warfarin exposure. Monitor patients for changes in dosing requirements during coadministration.
Mechanism Of Interaction
Induction of CYP3A4-mediated warfarin metabolism by mitotane
Literature Reports
A) After being admitted to the hospital with stage IV adrenal carcinoma and hip pain, Doppler studies revealed a left ileofemoral thrombus in a 58-year old woman. Streptokinase was instituted for 72 hours, followed by heparin therapy for eight days. Mitotane therapy was started on the sixth hospital day and was gradually titrated to a maintenance dose of 4 grams. Glucocorticoids, mineralocorticoids, oxycodone, acetaminophen, prochlorperazine, and clonidine were also given intermittently. After starting therapy with warfarin on the fourth hospital day, the patient's condition stabilized. The patient was discharged taking alternating daily warfarin doses of 5 mg and 2.5 mg. The patient's prothrombin times continued to be low during the three months after initiation of warfarin therapy, so warfarin doses were gradually increased to 12.5 mg per day. After experiencing a traumatic hematoma, the warfarin dose was decreased to a dose of 10 mg per day. Approximately six weeks later, the patient was admitted to the hospital with hematemesis, gingival bleeding, and lethargy which led to coma. A CT scan revealed hemorrhage of a metastatic tumor. Prothrombin times were measured at 74.6/11.3. The patient died that evening. The authors speculated that the increasing warfarin requirement in this patient was related to concomitant administration of mitotane, which was given at 4 grams per day throughout the patient's course. The mechanism of action was postulated to be mitotane acceleration of warfarin metabolism .
Warfarin Overview
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Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.
Mitotane Overview
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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.
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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.