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Drug Interactions between crizotinib and tolvaptan

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

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Interactions between your drugs

Moderate

tolvaptan crizotinib

Applies to: tolvaptan and crizotinib

GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of tolvaptan, which is almost exclusively metabolized by the isoenzyme. The interaction has been studied with ketoconazole, a potent CYP450 3A4 inhibitor. When a single 30 mg oral dose of tolvaptan was administered to 19 healthy volunteers following pretreatment with ketoconazole 200 mg/day for 3 days, tolvaptan peak plasma concentration (Cmax) increased by 3.5-fold and systemic exposure (AUC) increased by 5.4-fold, although 24-hour urine output increased by just 1.3-fold due to the saturable nature of tolvaptan's effect on urinary excretion rate. The impact of moderate CYP450 3A4 inhibitors has not been adequately assessed. According to the product labeling, grapefruit juice has been shown to increase tolvaptan exposure by 1.8-fold. However, the potency of grapefruit juice as an inhibitor of CYP450 3A4 depends on its strength, which was not specified.

MANAGEMENT: Concomitant use of tolvaptan with moderate CYP450 3A4 inhibitors should generally be avoided unless no alternatives exist and benefits outweigh potential risks. A lower dosage of tolvaptan should be considered. Serum sodium concentration and neurologic status should be closely monitored during coadministration. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death. Discontinuation or interruption of tolvaptan therapy should be considered in patients who develop too rapid a rise in serum sodium.

References

  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc

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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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Moderate

tolvaptan food

Applies to: tolvaptan

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.

References

  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American 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.

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