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Drug Interactions between mitotane and roflumilast

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

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Interactions between your drugs

Moderate

mitotane roflumilast

Applies to: mitotane and roflumilast

GENERALLY AVOID: Coadministration with potent CYP450 inducers may significantly reduce the systemic exposure to roflumilast and its pharmacologically active N-oxide metabolite, the former of which is metabolized by CYP450 1A2 and 3A4, and the latter of which is metabolized by CYP450 2C19 and 3A4. In 15 healthy volunteers, administration of a single 500 mcg oral dose of roflumilast in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 11 days) resulted in a 68% reduction of roflumilast peak plasma concentration (Cmax) and 80% reduction of systemic exposure (AUC) compared to administration of roflumilast alone. In addition, rifampin increased the Cmax of roflumilast N-oxide by 30% and decreased its AUC and half-life by 56% and 2.5-fold (from 24 to 9.9 hours), respectively. Total phosphodiesterase 4 inhibitory activity (i.e., combined effect of both roflumilast and roflumilast N-oxide) decreased by 58% in association with these changes.

MANAGEMENT: Due to the potential for reduced therapeutic effectiveness of roflumilast, concomitant use with potent CYP450 enzyme inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort is not recommended.

References (2)
  1. Nassr N, Huennemeyer A, Herzog R, et al. (2009) "Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects." Br J Clin Pharmacol, 68, p. 580-7
  2. (2011) "Product Information. Daliresp (roflumilast)." 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
Minor

roflumilast food

Applies to: roflumilast

Food intake does not affect the total exposure to roflumilast and its pharmacologically active N-oxide metabolite, but delays the time to maximum concentration (Tmax) of roflumilast by one hour and reduces its peak plasma concentration (Cmax) by approximately 40%. The Tmax and Cmax of
roflumilast N-oxide are unaffected. Roflumilast may be taken with or without food.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2011) "Product Information. Daxas (roflumilast)." Nycomed Inc
  3. (2011) "Product Information. Daliresp (roflumilast)." Astra-Zeneca Pharmaceuticals

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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