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Drug Interactions between Cardioquin and mifepristone

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

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Interactions between your drugs

Major

quiNIDine miFEPRIStone

Applies to: Cardioquin (quinidine) and mifepristone

CONTRAINDICATED: Coadministration with mifepristone may significantly increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by mifepristone. When a single 80 mg dose of simvastatin, a sensitive CYP450 3A4 substrate, was administered following pretreatment with mifepristone 1200 mg once daily for 10 days, simvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 7- and 10-fold, respectively. Likewise, the Cmax and AUC of simvastatin acid, the pharmacologically active metabolite, increased by approximately 18- and 16-fold, respectively.

MANAGEMENT: When mifepristone is used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, concomitant use of CYP450 3A4 substrates with narrow therapeutic ranges and high first-pass effect is considered contraindicated. These drugs include lovastatin, simvastatin, cyclosporine, ergot derivatives, fentanyl, oral midazolam, triazolam, pimozide, quinidine, sildenafil, sirolimus, and tacrolimus. The contraindication does not apply when mifepristone is used on a limited basis to terminate a pregnancy, but caution and close monitoring are advisable. 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. (2001) "Product Information. Mifeprex (mifepristone)." Danco Laboratories
  2. He K, Woolf TF, Hollenberg PF (1999) "Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486)." J Pharmacol Exp Ther, 288, p. 791-7
  3. (2012) "Product Information. Korlym (mifepristone)." Corcept Therapeutics Incorporated

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Cardioquin (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL (1983) "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos, 4, p. 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F (1995) "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol, 48, p. 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 4 references

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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

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

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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

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