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Drug Interactions between mitotane and osilodrostat

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

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Interactions between your drugs

Major

mitotane osilodrostat

Applies to: mitotane and osilodrostat

MONITOR CLOSELY: Coadministration with potent inducers of CYP450 3A4 and/or 2B6 may decrease the plasma concentrations of osilodrostat, which is partially metabolized by these isoenzymes. According to the product labeling, multiple CYP450 isoenzymes (CYP450 3A4, 2B6, and 2D6) and UDP-glucuronosyltransferases contribute to osilodrostat metabolism, and no single pathway contributes greater than 25% to the total clearance. Some of the known potent CYP450 3A4 and 2B6 inducers also induce UDP-glucuronosyltransferases. Pharmacokinetic data for osilodrostat in combination with a potent inducer of one or more of these pathways have not been reported. Reduced therapeutic efficacy of osilodrostat may occur during coadministration. On the other hand, discontinuation of a potent CYP450 3A4 and/or 2B6 inducer during treatment with osilodrostat may result in increased osilodrostat plasma concentrations and increased risk of adverse effects such as hypocortisolism (which may lead to life-threatening adrenal insufficiency), QT prolongation (which may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death), and elevated androgen and 11-deoxycorticosterone levels (the latter of which may activate mineralocorticoid receptors and cause hypokalemia, edema, and hypertension).

MANAGEMENT: An increase in the dosage of osilodrostat may be required during concomitant use of a potent CYP450 3A4 and/or 2B6 inducer. Dosage adjustments should be based on clinical response and tolerance. Patients should have regular monitoring of 24-hour urine free cortisol and serum or plasma cortisol during treatment, as well as regular evaluations of their signs and symptoms. A reduction in dosage of osilodrostat may be required if the potent CYP450 3A4 and/or 2B6 inducer is discontinued during treatment with osilodrostat.

References (3)
  1. (2020) "Product Information. Isturisa (osilodrostat)." Recordati Rare Diseases Inc
  2. (2022) "Product Information. Isturisa (osilodrostat)." (Obsolete) Recordati Rare Diseases Australia Pty Ltd, ISTURISA PI v1.1
  3. (2021) "Product Information. Isturisa (osilodrostat)." Recordati Rare Diseases UK Ltd

Drug and food interactions

Moderate

mitotane food

Applies to: mitotane

ADJUST DOSING INTERVAL: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

References (4)
  1. (2023) "Product Information. Lysodren (mitotane)." HRA Pharma America
  2. (2023) "Product Information. Lysodren (mitotane)." Medunik Canada
  3. (2023) "Product Information. Lysodren (mitotane)." HRA Pharma UK & Ireland Ltd
  4. Moolenaar AJ, van Slooten H, van Seters AP, Smeenk D (2023) Blood levels of o,p-DDD following administration in various vehicles after a single dose and during long-term treatment https://link.springer.com/article/10.1007/BF00258213

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Adrenal corticosteroid inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'adrenal corticosteroid inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'adrenal corticosteroid inhibitors' category:

  • mitotane
  • osilodrostat

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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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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