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Drug Interactions between brexpiprazole and ivacaftor / lumacaftor

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

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Interactions between your drugs

Major

lumacaftor brexpiprazole

Applies to: ivacaftor / lumacaftor and brexpiprazole

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of brexpiprazole. In vitro and in vivo data indicate that brexpiprazole is metabolized primarily by CYP450 3A4 and 2D6. When a single 4 mg oral dose of brexpiprazole was administered to healthy study subjects treated with the potent CYP450 3A4 inducer rifampin at 600 mg twice daily for 12 days, mean brexpiprazole peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 31% and 73%, respectively, compared to administration of brexpiprazole alone. Reduced efficacy of brexpiprazole may occur.

MANAGEMENT: The prescribing information for brexpiprazole recommends doubling the usual dosage over 1 to 2 weeks following the addition of a potent CYP450 3A4 inducer. Additional dosage adjustments should be based on clinical evaluation. Upon discontinuation of the inducer, brexpiprazole dosage should be reduced to the original level over 1 to 2 weeks.

References

  1. (2023) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
  2. (2020) "Product Information. Rexulti (brexpiprazole)." Otsuka Pharmaceutical Co Ltd
  3. (2020) "Product Information. Rexulti (brexpiprazole)." Lundbeck Australia Pty Ltd

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Drug and food interactions

Moderate

ivacaftor food

Applies to: ivacaftor / lumacaftor

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
View all 4 references

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Moderate

brexpiprazole food

Applies to: brexpiprazole

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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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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