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Drug Interactions between crizotinib and Mebaral

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

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Interactions between your drugs

Moderate

mephobarbital crizotinib

Applies to: Mebaral (mephobarbital) and crizotinib

MONITOR: Coadministration with CYP450 3A4 inducers may decrease plasma concentrations and pharmacologic effects of crizotinib, which is primarily metabolized by the isoenzyme. In study subjects, administration of a single 250 mg oral dose of crizotinib during treatment with the strong CYP450 3A4 inducer rifampin (600 mg once daily) resulted in an approximately 69% decrease in crizotinib peak plasma concentration (Cmax) and an 82% decrease in systemic exposure (AUC) compared to crizotinib administered alone. Crizotinib steady state Cmax and AUCinf decreased by 79% and 84%, respectively, following repeated coadministration of crizotinib (250 mg twice daily) and rifampin (600 mg once daily) compared to crizotinib alone. The extent to which mild to moderate CYP450 3A4 inducers may interact with crizotinib is unknown.

MANAGEMENT: Caution and clinical monitoring should be considered if CYP450 3A4 inducers such as efavirenz are used with crizotinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group
  3. Cerner Multum, Inc. (2015) "Canadian Product Information."

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Drug and food interactions

Major

crizotinib food

Applies to: crizotinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.

References

  1. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group

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Major

mephobarbital food

Applies to: Mebaral (mephobarbital)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 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.

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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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