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Drug Interactions between Lysodren and osimertinib

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

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Interactions between your drugs

Major

mitotane osimertinib

Applies to: Lysodren (mitotane) and osimertinib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of osimertinib, which has been shown in vitro to be primarily metabolized by the isoenzyme. Reduced therapeutic efficacy of osimertinib should be anticipated. In a clinical pharmacokinetic study, the osimertinib systemic exposure (AUC) at steady state was reduced by 78% when given concomitantly with the potent CYP450 3A4 inducer rifampin (600 mg daily for 21 days). In addition, the AUC and peak plasma concentration (Cmax) of the pharmacologically active metabolite of osimertinib, AZ5104, also decreased by 82% and 78%, respectively.

MANAGEMENT: Concomitant use of osimertinib with potent CYP450 3A4 inducers should generally be avoided. However, if concomitant use is required, some authorities recommend increasing the dose of osimertinib to 160 mg daily during treatment with the potent 3A4 inducer and resumed at 80 mg daily, 3 weeks after discontinuation of the potent 3A4 inducer.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2015) "Product Information. Tagrisso (osimertinib)." Astra-Zeneca Pharmaceuticals

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Drug and food interactions

Moderate

mitotane food

Applies to: Lysodren (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

  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
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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.

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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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