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Drug Interactions between mitotane and Seroquel

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

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Interactions between your drugs

Major

mitotane QUEtiapine

Applies to: mitotane and Seroquel (quetiapine)

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of quetiapine, which is primarily metabolized by the isoenzyme. In 18 psychiatric patients receiving quetiapine 300 mg twice daily, addition of the potent CYP450 3A4 inducer carbamazepine (200 mg three times daily) decreased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 87%, respectively, and increased oral clearance (Cl/F) by 7.5-fold compared to quetiapine administered alone. The interaction has also been reported with phenytoin, another potent CYP450 3A4 inducer. In ten subjects with various affective disorders, coadministration of quetiapine (250 mg orally three times a day) with phenytoin (100 mg orally three times a day) decreased the mean steady-state Cmax, trough plasma concentration (Cmin) and AUC of quetiapine by 66%, 89% and 80%, respectively. The mean oral clearance increased by 5.5-fold.

MANAGEMENT: Increased dosages of quetiapine may be required during chronic treatment (greater than 7 to 14 days) with potent CYP450 3A4 inducers. The manufacturer recommends an increase of up to 5-fold the original dosage of quetiapine. Further adjustments should be made based on clinical response and tolerance. The safety of dosages above 800 mg/day has not been established in clinical trials. Continued treatment at higher dosages should only be considered following careful consideration of risks and benefits. When the CYP450 3A4 inducer is discontinued, the dosage of quetiapine should be reduced to the original level within 7 to 14 days.

References (5)
  1. (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
  2. (1997) "Quetiapine for schizophrenia." Med Lett Drugs Ther, 39, p. 117-8
  3. Wong YWJ, Yeh C, Thyrum PT (2001) "The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine." J Clin Psychopharmacol, 21, p. 89-93
  4. Grimm SW, Richtand NM, Winter HR, Stams KR, Reele SB (2006) "Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics." Br J Clin Pharmacol, 61, p. 58-69
  5. Cerner Multum, Inc. "Australian Product Information."

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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