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Drug Interactions between atazanavir / cobicistat and Korlym

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

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Interactions between your drugs

Major

miFEPRIStone atazanavir

Applies to: Korlym (mifepristone) and atazanavir / cobicistat

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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Major

miFEPRIStone cobicistat

Applies to: Korlym (mifepristone) and atazanavir / cobicistat

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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Drug and food interactions

Moderate

miFEPRIStone food

Applies to: Korlym (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

atazanavir food

Applies to: atazanavir / cobicistat

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):

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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.

See also

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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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