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Drug Interactions between mifepristone and Xenleta

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

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Interactions between your drugs

Major

miFEPRIStone lefamulin

Applies to: mifepristone and Xenleta (lefamulin)

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."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2012) "Product Information. Korlym (mifepristone)." Corcept Therapeutics Incorporated
View all 4 references

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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

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

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Moderate

lefamulin food

Applies to: Xenleta (lefamulin)

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of lefamulin. When a single 600 mg oral dose of lefamulin was administered with a high-calorie, high-fat breakfast (800 to 1000 calories; approximately 50% from fat), lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 23% and 18%, respectively.

GENERALLY AVOID: Grapefruit juice may increase the oral bioavailability of lefamulin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, ketoconazole. When oral lefamulin was administered with oral ketoconazole, mean lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 58% and 165%, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to lefamulin may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Lefamulin tablets should be taken at least one hour before or two hours after a meal. Patients should preferably avoid or limit the consumption of grapefruit and grapefruit juice during treatment with lefamulin.

References

  1. (2019) "Product Information. Xenleta (lefamulin)." Nabriva Therapeutics US, Inc.

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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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