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Drug Interactions between mefloquine and selpercatinib

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

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Interactions between your drugs

Major

mefloquine selpercatinib

Applies to: mefloquine and selpercatinib

MONITOR CLOSELY: Selpercatinib can cause concentration-dependent prolongation of the QT interval. 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. Based on findings from a thorough QT study in healthy subjects, the largest mean increase in QTc is predicted to be 10.6 msec (upper 90% confidence interval: 12.1 msec) at the mean steady-state maximum concentration (Cmax) observed in patients administered selpercatinib 160 mg twice daily. In clinical trials, an increase in QTcF interval to >500 msec was measured in 6% of patients and an increase in the QTcF interval of at least 60 msec over baseline was measured in 15% of patients. Selpercatinib has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. 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, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if selpercatinib is used in combination with other drugs that can prolong the QT interval. An electrocardiogram and serum electrolyte levels should be obtained prior to initiating selpercatinib therapy and periodically during treatment as appropriate based on individual risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and/or hypocalcemia before starting treatment and during treatment, as they may be risk factors for ventricular arrhythmias. Selpercatinib treatment should be discontinued, interrupted, or dosage reduced based on severity of QT prolongation and/or development of arrhythmia in accordance with the product labeling. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company

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Drug and food interactions

Major

selpercatinib food

Applies to: selpercatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selpercatinib. 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 has been reported for other CYP450 3A4 inhibitors. When selpercatinib was coadministered with multiple doses of itraconazole, a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Based on pharmacokinetic modeling, administration of selpercatinib with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem, fluconazole, or verapamil is predicted to increase selpercatinib Cmax by 46% to 76% and AUC by 60% to 99%. 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 selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).

MANAGEMENT: Patients should limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company

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Moderate

mefloquine food

Applies to: mefloquine

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of mefloquine. The proposed mechanism is increased drug solubility in the presence of food. In 20 healthy volunteers, administration of a single 750 mg oral dose of mefloquine 30 minutes following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of mefloquine by 73% and 40%, respectively, compared to administration in the fasting state. The Cmax and AUC of the carboxylic acid metabolite were also increased by 35% and 33%, respectively, compared to fasting. In addition, the time to reach peak plasma concentration (Tmax) of mefloquine was significantly shorter after food intake (17 hours) than in the fasting state (36 hours). There was no difference in the elimination half-life of mefloquine and metabolite, or the Tmax for the metabolite.

MANAGEMENT: To ensure maximal oral absorption, mefloquine should be administered immediately after a meal with at least 8 ounces of water.

References

  1. (2021) "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
  2. Schmidt LE, Dalhoff K (2002) "Food-drug interactions." Drugs, 62, p. 1481-502

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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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