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Drug Interactions between brigatinib and fluvoxamine

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

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Interactions between your drugs

Moderate

fluvoxaMINE brigatinib

Applies to: fluvoxamine and brigatinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of brigatinib, which is partially metabolized by the isoenzyme. When a single 90 mg dose of brigatinib was administered with the potent CYP450 3A4 inhibitor itraconazole (200 mg twice daily), brigatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 21% and 101%, respectively, compared to brigatinib administered alone. Simulations from a physiologically-based pharmacokinetic model predict a moderate CYP450 3A4 inhibitor may increase the AUC of brigatinib by approximately 40%. It is not known to what extent brigatinib may interact with weak CYP450 3A4 inhibitors.

MANAGEMENT: If coadministration with CYP450 3A4 inhibitors is needed, patients should be closely monitored for increased adverse reactions such as nausea, vomiting, diarrhea, hypertension, bradycardia, hyperglycemia, visual disturbances, lymphopenia, anemia, and elevations in pancreatic enzymes and creatine phosphokinase.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2017) "Product Information. Alunbrig (brigatinib)." Ariad Pharmaceuticals Inc

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Drug and food interactions

Moderate

fluvoxaMINE food

Applies to: fluvoxamine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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

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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.