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Drug Interactions between Carnexiv and probenecid

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

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Interactions between your drugs

Minor

probenecid carBAMazepine

Applies to: probenecid and Carnexiv (carbamazepine)

Coadministration with probenecid may increase the metabolism of carbamazepine to carbamazepine 10,11-epoxide. The proposed mechanism is induction of CYP450 3A4 and 2C8 activities by probenecid. In 10 healthy volunteers, pretreatment with probenecid (500 mg orally twice daily for 10 days) resulted in a 19% decrease in the area under the plasma concentration-time curve (AUC) of carbamazepine (200 mg single oral dose on day 6) compared to placebo, while AUC of carbamazepine 10,11-epoxide increased 33% by probenecid relative to placebo. Probenecid also increased the oral clearance of carbamazepine by 26% and the AUC ratio of the epoxide metabolite to carbamazepine by 45%. The clinical significance of these changes is unknown.

References

  1. Kim KA, Oh SO, Park PW, Park JY (2005) "Effect of probenecid on the pharmacokinetics of carbamazepine in healthy subjects." Eur J Clin Pharmacol, 61, p. 275-80

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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. (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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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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