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Drug Interactions between mitotane and vandetanib

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

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Interactions between your drugs

Moderate

mitotane vandetanib

Applies to: mitotane and vandetanib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of vandetanib, which is a substrate of the isoenzyme. In 16 healthy male subjects, coadministration of rifampin (600 mg/day on days 1 to 31) and vandetanib (single 300 mg oral dose on day 10) resulted in an approximately 40% decrease in vandetanib exposure (AUC) and almost 50% decrease in half-life (from 217.6 hours to 116.3 hours) compared to vandetanib administered alone. There was no significant change in the peak plasma concentration (Cmax) of vandetanib. In the presence of rifampin, the Cmax and AUC of a metabolite, N-desmethylvandetanib, increased by 414% and 266%, respectively. Rifampin also increased the Cmax and AUC of another metabolite, vandetanib N-oxide, by approximately 179% and 126%, respectively. However, the plasma concentrations of vandetanib N-oxide were very low throughout, thus the change in absolute plasma levels induced by rifampin was actually quite small. The clinical implications of these changes are unknown. The two metabolites have shown in vitro pharmacologic activity in cellular assays against vascular endothelial growth factor and epidermal growth factor, with N-desmethylvandetanib exhibiting similar potency to parent drug and vandetanib N-oxide exhibiting less than 1/50 the activity of the parent drug.

MANAGEMENT: Concomitant use of vandetanib with potent CYP450 3A4 inducers should generally be avoided.

References (2)
  1. Martin P, Oliver S, Robertson J, Kennedy SJ, Read J, Duvauchelle T (2011) "Pharmacokinetic drug interactions with vandetanib during cadministration with rifampicin or itraconazole." Drugs R D, 11, p. 37-51
  2. (2011) "Product Information. Vandetanib (vandetanib)." Astra-Zeneca Pharmaceuticals

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

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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