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Drug Interactions between felbamate and Odomzo

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

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Interactions between your drugs

Moderate

felbamate sonidegib

Applies to: felbamate and Odomzo (sonidegib)

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of sonidegib, which is primarily metabolized by the isoenzyme. In 16 healthy volunteers, administration of a single 800 mg dose of sonidegib five days after starting treatment with the potent CYP450 3A4 inducer rifampin (600 mg daily for 14 days) decreased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 54% and 72%, respectively, compared to administration of sonidegib alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that sonidegib steady-state AUC would decrease 56% in cancer patients taking sonidegib 200 mg once daily with the moderate CYP450 3A4 inducer efavirenz for 14 days, and 69% when coadministered with efavirenz for 4 months. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of sonidegib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

References

  1. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

felbamate food

Applies to: felbamate

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

sonidegib food

Applies to: Odomzo (sonidegib)

ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of sonidegib. According to the product labeling, administration of sonidegib with a high-fat meal (approximately 1000 calories; 50% from fat) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 7.4- to 7.8-fold.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of sonidegib. 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. Increased exposure to sonidegib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, nausea, vomiting, diarrhea, anorexia, weight loss, alopecia, pruritus, and dysgeusia.

MANAGEMENT: Sonidegib should be administered on an empty stomach, at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with sonidegib.

References

  1. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

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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.