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Drug Interactions between mifepristone and Tepadina

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

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Interactions between your drugs

Major

thiotepa miFEPRIStone

Applies to: Tepadina (thiotepa) and mifepristone

GENERALLY AVOID: Coadministration with strong CYP450 3A4 inhibitors may increase plasma concentrations of thiotepa, and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by the isoenzyme. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure. Although clinical evidence is limited, strong CYP450 3A4 inhibitors may more significantly increase thiotepa exposure and reduce TEPA exposure, potentially resulting in more thiotepa-related adverse effects and reduced efficacy.

MANAGEMENT: The use of thiotepa in combination with strong CYP450 3A4 inhibitors should generally be avoided. If concomitant use of a strong CYP450 3A4 inhibitor is required, it is recommended that patients be carefully monitored for reduced efficacy and thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity.

References (5)
  1. de Jonge ME, Huitema AD, Holtkamp MJ, van Dam SM, Beijnen JH, Rodenhuis S (2005) "Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism" Cancer Chemother Pharmacol, 56, p. 370-8
  2. (2023) "Product Information. Thiotepa (thiotepa)." Meitheal Pharmaceuticals Inc.
  3. (2023) "Product Information. Tepadina (thiotepa)." Link Medical Products Pty Ltd T/A Link Pharmaceuticals, 3
  4. (2022) "Product Information. Thiotepa (thiotepa)." MSN Laboratories Europe Ltd
  5. (2021) "Product Information. Tepadina (thiotepa)." Adienne SA

Drug and food interactions

Moderate

miFEPRIStone food

Applies to: mifepristone

ADJUST DOSING INTERVAL: Food may significantly increase the plasma concentrations of mifepristone.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mifepristone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: When mifepristone is used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, it should be taken with food to achieve consistent plasma drug levels. Patients should be advised to avoid consuming grapefruit or grapefruit juice during treatment with mifepristone, as it may cause increased adverse effects such as headache, dizziness, fatigue, nausea, vomiting, cramping, diarrhea, hypokalemia, adrenal insufficiency, vaginal bleeding, arthralgia, peripheral edema, and hypertension. Because mifepristone is eliminated slowly from the body, the interaction with grapefruit juice may be observed for a prolonged period.

References (2)
  1. (2001) "Product Information. Mifeprex (mifepristone)." Danco Laboratories
  2. (2012) "Product Information. Korlym (mifepristone)." Corcept Therapeutics Incorporated

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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