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Drug Interactions between brigatinib and cimetidine

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

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Interactions between your drugs

Moderate

cimetidine brigatinib

Applies to: cimetidine 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. "Product Information. Alunbrig (brigatinib)." Ariad Pharmaceuticals Inc (2017):

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Drug and food interactions

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

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Minor

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: cimetidine

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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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

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

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