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Drug Interactions between Erythrocot and Mifeprex

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

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Interactions between your drugs

Major

erythromycin miFEPRIStone

Applies to: Erythrocot (erythromycin) and Mifeprex (mifepristone)

GENERALLY AVOID: Mifepristone may prolong the QTc interval in a dose-related manner. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Mifepristone and its metabolites have been found to inhibit the hERG-encoded cardiac potassium channels responsible for the rapid delayed rectifier K+ (IKr) repolarizing current. However, there is little or no experience with high exposure, concomitant dosing with other QT-prolonging drugs, or potassium channel variants resulting in a long QT interval. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Since mifepristone can commonly cause hypokalemia during prolonged use, this should also be considered during coadministration with other QT-prolonging drugs. In a study of patients with Cushing's syndrome, hypokalemia was observed in 44% of subjects treated with mifepristone. The hypokalemia responded to treatment with potassium supplementation and/or mineralocorticoid antagonist therapy (e.g., spironolactone or eplerenone).

MANAGEMENT: When mifepristone is used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, coadministration with other drugs that can prolong the QT interval should generally be avoided. Caution is recommended if no alternatives exist and concomitant use is required. Serum potassium should be assessed prior to starting mifepristone and 1 to 2 weeks following initiation of therapy or an increase in dosage, and periodically as needed. Hypokalemia must be corrected prior to initiation of mifepristone. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hypokalemia such as fatigue, weakness, myalgia, muscle cramps, numbness, tingling, abdominal pain, constipation, palpitation, and irregular heart rhythm. 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. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Korlym (mifepristone)." Corcept Therapeutics Incorporated (2012):
View all 4 references

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Drug and food interactions

Moderate

erythromycin food

Applies to: Erythrocot (erythromycin)

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

References

  1. Welling PG, Huang H, Hewitt PF, Lyons LL "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci 67 (1978): 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci 68 (1979): 150-5
  3. Welling PG "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm 5 (1977): 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol 18 (1978): 194-202
  5. Malmborg AS "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother 5 (1979): 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol 29 (1989): 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol 56 (2001): 799-803
View all 7 references

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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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Minor

erythromycin food

Applies to: Erythrocot (erythromycin)

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

References

  1. Morasso MI, Chavez J, Gai MN, Arancibia A "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol 28 (1990): 426-9

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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.

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