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Drug Interactions between cabozantinib and Tegretol XR

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

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Interactions between your drugs

Major

carBAMazepine cabozantinib

Applies to: Tegretol XR (carbamazepine) and cabozantinib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of cabozantinib, which is a substrate of the isoenzyme. In healthy subjects, administration of the potent CYP450 3A4 inducer rifampin (600 mg daily for 31 days) decreased single-dose cabozantinib plasma exposure (AUC) by 77%. Reduced therapeutic efficacy of cabozantinib may occur.

MANAGEMENT: Chronic use of potent CYP450 3A4 inducers during treatment with cabozantinib should be avoided whenever possible. If chronic coadministration is required, the daily dosage of cabozantinib should be increased in accordance with the prescribing information for the specific product. For the treatment of progressive, metastatic medullary thyroid cancer (capsule formulation), the recommendation is to increase cabozantinib dosage by 40 mg (e.g., from 140 mg to 180 mg daily or from 100 mg to 140 mg daily) as tolerated, not to exceed 180 mg/day. For the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy (tablet formulation), the recommendation is to increase cabozantinib dosage by 20 mg (e.g., from 60 mg to 80 mg daily or from 40 mg to 60 mg daily) as tolerated, not to exceed 80 mg/day. The original dosage of cabozantinib may be resumed 2 to 3 days after discontinuation of the potent CYP450 3A4 inducer.

References

  1. (2012) "Product Information. Cometriq (cabozantinib)." Exelixis Inc
  2. (2016) "Product Information. Cabometyx (cabozantinib)." Exelixis Inc

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Tegretol XR (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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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. (2012) "Product Information. Cometriq (cabozantinib)." Exelixis 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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