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Drug Interactions between cabozantinib and Samsca

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

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Interactions between your drugs

Moderate

tolvaptan cabozantinib

Applies to: Samsca (tolvaptan) and cabozantinib

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the oral bioavailability of tolvaptan, which has been shown in vitro to be a substrate of the efflux transporter. Pharmacokinetic and clinical data are not available, however.

MANAGEMENT: Caution is advised if tolvaptan is prescribed in combination with P-glycoprotein inhibitors, especially potent ones such as amiodarone, cyclosporine, or quinidine. Serum sodium concentration and neurologic status should be closely monitored, and the tolvaptan dosage adjusted accordingly. 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. "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc (2009):

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Drug and food interactions

Moderate

tolvaptan food

Applies to: Samsca (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. "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc (2009):

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Moderate

cabozantinib food

Applies to: cabozantinib

ADJUST DOSING INTERVAL: Food may alter the oral bioavailability of cabozantinib. When healthy subjects were given a single 140 mg oral dose with a high-fat meal, cabozantinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 41% and 57%, respectively, relative to administration under fasting conditions. In clinical studies, patients were administered cabozantinib without food.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of cabozantinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Cabozantinib should be administered at least one hour before or two hours after a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.

References

  1. "Product Information. Cometriq (cabozantinib)." Exelixis Inc (2012):

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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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