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Drug Interactions between Carnexiv and Gleevec

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

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Interactions between your drugs

Major

carBAMazepine imatinib

Applies to: Carnexiv (carbamazepine) and Gleevec (imatinib)

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of imatinib, which is primarily metabolized by the isoenzyme. Therapeutic failure may occur. When a single 400 mg oral dose of imatinib was administered to 14 healthy adult volunteers following pretreatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), mean imatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 54% and 74%, respectively, compared to administration alone. The oral clearance of imatinib was increased by 3.8-fold during rifampin coadministration. Similar results were observed in patients with malignant gliomas receiving imatinib 400 to 1200 mg/day concomitantly with enzyme-inducing antiepileptic drugs (EIAEDs) such as carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, and primidone. The mean dose-normalized AUC for imatinib decreased by 73% compared to patients not on EIAEDs. In two published studies, concomitant administration of imatinib and a product containing St. John's wort led to a 30% to 32% reduction in the AUC of imatinib.

MANAGEMENT: Concomitant use of imatinib with potent CYP450 3A4 inducers should generally be avoided. Alternative therapeutic agents with less enzyme induction potential should be considered whenever possible. If coadministration with a potent CYP450 3A4 inducer is required, some authorities recommend increasing the dosage of imatinib by at least 50% while carefully monitoring clinical response. Imatinib dosages up to 1200 mg/day (600 mg twice daily) have been given to patients receiving concomitant potent CYP450 3A4 inducers.

References

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. Bolton AE, Peng B, Hubert M, et al. "Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects." Cancer Chemother Pharmacol 53 (2004): 102-6
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  5. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  6. Cerner Multum, Inc. "Australian Product Information." O 0
View all 6 references

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Drug and food interactions

Moderate

carBAMazepine food

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

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Moderate

imatinib food

Applies to: Gleevec (imatinib)

GENERALLY AVOID: Coadministration of imatinib with strong CYP450 3A4 inhibitors such as grapefruit juice, may significantly increase the plasma concentrations of imatinib, a known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of imatinib by certain compounds present in grapefruits. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. In a single-dose study, coadministration of imatinib with ketoconazole (a strong CYP450 3A4 inhibitor) increased imatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 26% and 40%, respectively.

MANAGEMENT: Patients treated with imatinib should preferably avoid the consumption of grapefruit or grapefruit juice. If coadministration is unavoidable, monitor for prolonged and/or increased pharmacologic effects of imatinib, including edema, hematologic toxicity and immunosuppression.

References

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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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

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