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Drug Interactions between macimorelin and selpercatinib

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

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Interactions between your drugs

Major

macimorelin selpercatinib

Applies to: macimorelin and selpercatinib

GENERALLY AVOID: Macimorelin can cause 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. In a dedicated thorough QT study consisting of 60 healthy subjects, a mean baseline- and placebo-adjusted change in QTcF of 9.6 msec was observed 4 hours following administration of a supratherapeutic dose of macimorelin 2 mg/kg (4 times the recommended dose), which occurred after the mean maximum macimorelin plasma concentration (0.5 hour). A similar increase in the QTcF interval was also observed in a single-ascending dose study, which included three dose levels: 0.5 mg/kg; 1 mg/kg (2 times the recommended dose); and 2 mg/kg (4 times the recommended dose). All three doses levels produced a similar magnitude of QTcF prolongation as reported in the thorough QT study, suggesting an absence of dose-dependent changes. The mechanism for the observed QTcF prolongation is unknown. 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). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of macimorelin with other drugs that can prolong the QT interval should generally be avoided. A sufficient washout period following discontinuation of these drugs is recommended prior to macimorelin administration. Patients treated with any medication that can cause QT prolongation 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)
  1. (2018) "Product Information. Macrilen (macimorelin)." Aeterna Zentaris

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 a single dose of selpercatinib (160 mg) was coadministered with multiple doses of itraconazole (200 mg once daily), 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 multiple doses of selpercatinib (160 mg twice daily) with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem (60 mg three times daily), fluconazole (200 mg once daily), or verapamil (80 mg three times daily) 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: Until further information is available, it may be advisable for patients to limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.

References (4)
  1. (2024) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
  2. (2023) "Product Information. Retevmo (selpercatinib)." Eli Lilly Australia Pty Ltd, vA1.0
  3. (2024) "Product Information. Retsevmo (selpercatinib)." Eli Lilly and Company Ltd
  4. (2024) "Product Information. Retevmo (selpercatinib)." Loxo Oncology Inc
Moderate

macimorelin food

Applies to: macimorelin

ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of macimorelin. According to the product labeling, administration with a liquid meal decreased macimorelin peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 49%, respectively, compared to administration under fasting conditions (i.e., for at least 8 hours).

MANAGEMENT: Macimorelin should be administered after fasting for at least 8 hours.

References (1)
  1. (2018) "Product Information. Macrilen (macimorelin)." Aeterna Zentaris

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

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