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Drug Interactions between Alecensa and brigatinib

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

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Interactions between your drugs

Moderate

alectinib brigatinib

Applies to: Alecensa (alectinib) and brigatinib

MONITOR: Coadministration of brigatinib with other agents that can also slow the heart rate may potentiate the risk of severe bradycardia. In one clinical trial, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients who received brigatinib 90 mg and 7.6% of patients who had the dosage increased from 90 mgto 180 mg. Grade 2 bradycardia occurred in 0.9% of patients in the 90 mg group.

MANAGEMENT: Caution is advised if brigatinib is used concomitantly with beta-blockers, calcium channel blockers, digitalis, or other drugs that can slow the heart rate or atrioventricular conduction such as alectinib, atazanavir, fingolimod, flecainide, ivabradine, lacosamide, lithium, mefloquine, moricizine, propafenone, succinylcholine, thalidomide, H2-receptor antagonists, tricyclic antidepressants, and anticholinesterase or cholinergic agents. Heart rate and blood pressure should be monitored frequently, and patients should be advised to seek medical attention if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. For symptomatic bradycardia, withhold brigatinib until recovery to asymptomatic bradycardia or to a resting heart rate >=60 bpm, then resume brigatinib (at the same or reduced dose depending on whether concomitant medication is discontinued or dose-adjusted) or permanently discontinue in accordance with the recommendations in the product labeling.

References (1)
  1. (2017) "Product Information. Alunbrig (brigatinib)." Ariad Pharmaceuticals Inc

Drug and food interactions

Moderate

alectinib food

Applies to: Alecensa (alectinib)

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of alectinib and its major active metabolite, M4. According to the manufacturer, a high-fat, high-calorie meal increased the combined systemic exposure (AUC) of alectinib and M4 by 3.1-fold following oral administration of a single 600 mg dose of alectinib.

MANAGEMENT: To ensure maximal oral absorption, alectinib should be administered with food.

References (1)
  1. (2015) "Product Information. Alecensa (alectinib)." Genentech
Moderate

brigatinib food

Applies to: brigatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of brigatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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. Itraconazole, a potent CYP450 3A4 inhibitor, has been shown to double brigatinib systemic exposure (AUC) in healthy volunteers. Increased exposure to brigatinib may increase the risk of adverse effects such as nausea, vomiting, diarrhea, hypertension, bradycardia, hyperglycemia, visual disturbances, lymphopenia, anemia, and elevations in pancreatic enzymes and creatine phosphokinase.

Food does not significantly affect the oral bioavailability of brigatinib. When brigatinib was administered to healthy volunteers after a high-fat meal (920 calories; 59 g fat, 58 g carbohydrates, 40 g proteins), brigatinib peak plasma concentration (Cmax) decreased by 13% and systemic exposure (AUC) did not change compared to administration after overnight fasting.

MANAGEMENT: Brigatinib may be taken with or without food. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with brigatinib.

References (1)
  1. (2017) "Product Information. Alunbrig (brigatinib)." Ariad Pharmaceuticals Inc

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Multikinase inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

  • Alecensa (alectinib)
  • brigatinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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

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

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