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Drug Interactions between axitinib and mitotane

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

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Interactions between your drugs

Major

mitotane axitinib

Applies to: mitotane and axitinib

GENERALLY AVOID: Coadministration with potent and moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of axitinib, which is primarily metabolized by the isoenzyme. In a study of 40 healthy, nonsmoking, male volunteers, administration of a single 5 mg dose of axitinib on day 8 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg/day for 9 days) resulted in a 71% decrease in mean axitinib peak plasma concentration (Cmax) and 79% decrease in mean systemic exposure. The extent to which other, less potent inducers of CYP450 3A4 may interact with axitinib is unknown.

MANAGEMENT: Concomitant use of axitinib with potent CYP450 3A4 inducers such as apalutamide, carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided. Although pharmacokinetic data are lacking, the manufacturer recommends that moderate CYP450 3A4 inducers should also be avoided if possible, including but not limited to bosentan, cenobamate, dabrafenib, dexamethasone, efavirenz, etravirine, lorlatinib, modafinil, nafcillin, pexidartinib, and sotorasib.

References (2)
  1. (2012) "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group
  2. Pithavala YK, Tortorici M, Toh M, et al. (2010) "Effect of rifampin on the pharmacokinetics of axitinib (AG-013736) in Japanese and Caucasian healthy volunteers." Cancer Chemother Pharmacol, 65, p. 563-70

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
Moderate

axitinib food

Applies to: axitinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.

References (1)
  1. (2012) "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group

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

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