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Drug Interactions between macimorelin and pacritinib

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

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Interactions between your drugs

Major

macimorelin pacritinib

Applies to: macimorelin and pacritinib

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

pacritinib food

Applies to: pacritinib

GENERALLY AVOID: Theoretically, coadministration with grapefruit juice may increase the plasma concentrations of pacritinib, which is primarily metabolized by CYP450 3A4. 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 the potent CYP450 3A4 inhibitor, clarithromycin. In a clinical drug interaction study, a single dose of pacritinib (400 mg) was administered following treatment with clarithromycin (500 mg twice daily for 5 days). The peak plasma concentration (Cmax) and systemic exposure (AUC) of pacritinib increased by 30% and 80%, respectively, compared to pacritinib administered alone. Longer treatment with clarithromycin that results in maximal CYP450 3A4 inhibition may increase pacritinib exposure even higher. 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 pacritinib may increase the risk of adverse effects such as diarrhea, thrombocytopenia, infection, and QT prolongation.

Pacritinib pharmacokinetics were not significantly affected when administered with a high-fat meal.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid consumption of grapefruit or grapefruit juice during treatment with pacritinib. Pacritinib may be administered with or without food.

References (1)
  1. (2022) "Product Information. Vonjo (pacritinib)." CTI BioPharma Corp.
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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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