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Drug Interactions between cobicistat / darunavir and Mifeprex

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

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Interactions between your drugs

Major

miFEPRIStone cobicistat

Applies to: Mifeprex (mifepristone) and cobicistat / darunavir

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of mifepristone, which is primarily metabolized by the isoenzyme. The clinical impact of this interaction has not been studied.

MANAGEMENT: Due to its potent antiglucocorticoid effects and potential to cause dose-related prolongation of the QT interval, extreme caution is advised when mifepristone is prescribed in combination with strong CYP450 3A4 inhibitors such as, but not limited to, itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, conivaptan, delavirdine, nefazodone, telithromycin, and protease inhibitors. When used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, the dosage of mifepristone should be limited to 300 mg/day and used only when necessary.

References

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

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Moderate

miFEPRIStone darunavir

Applies to: Mifeprex (mifepristone) and cobicistat / darunavir

MONITOR: Coadministration of mifepristone with a drug that is both a substrate as well as inhibitor of CYP450 3A4 may result in increased plasma concentrations of both drugs. Mifepristone itself is also a substrate and moderate inhibitor of CYP450 3A4. Theoretically, competitive and/or noncompetitive metabolic inhibition may occur. Because mifepristone is associated with dose-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Due to its potent antiglucocorticoid effects and potential to cause dose-related prolongation of the QT interval, caution is advised if mifepristone is prescribed in combination with a CYP450 3A4 inhibitor, particularly when used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome. When the coadministered drug is also a CYP450 3A4 substrate, clinical and/or laboratory monitoring may be appropriate following the addition or withdrawal of mifepristone, and the dosage adjusted as necessary. Because mifepristone is eliminated slowly from the body, drug interactions may be observed for a prolonged period following discontinuation (approximately 2 to 3 weeks if mifepristone had been administered chronically to steady state).

References

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

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Drug and food interactions

Moderate

miFEPRIStone food

Applies to: Mifeprex (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

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

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Moderate

darunavir food

Applies to: cobicistat / darunavir

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):

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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.