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Drug Interactions between Epitol and fluconazole

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

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Interactions between your drugs

Moderate

carBAMazepine fluconazole

Applies to: Epitol (carbamazepine) and fluconazole

MONITOR: Coadministration with fluconazole may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4-mediated metabolism by fluconazole, a moderate inhibitor of the isoenzyme. A 30% increase in serum carbamazepine has been observed during coadministration with fluconazole according to the product labeling. There have also been a few isolated case reports in the medical literature describing an approximate doubling of carbamazepine levels following the addition of fluconazole, resulting in toxicity. Other drugs metabolized by CYP450 3A4 whose plasma levels reportedly are increased by fluconazole include oral contraceptives (ethinyl estradiol and levonorgestrel), cyclosporine, tacrolimus, and cisapride. These interactions have usually been observed with higher dosages of fluconazole (200 mg/day or more).

MANAGEMENT: Caution is advised when fluconazole is used with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever fluconazole is added to or withdrawn from therapy.

References

  1. Sugar AM, Saunders C, Idelson BA, Bernard DB (1989) "Interaction of fluconazole and cyclosporine." Ann Intern Med, 110, p. 844
  2. Canafax DM, Graves NM, Hilligoss DM, et al. (1991) "Interaction between cyclosporine and fluconazole in renal allograft recipients." Transplantation, 51, p. 1014-8
  3. Torregrosa V, De la Torre M, Campistol JM, et al. (1992) "Interaction of fluconazole with ciclosporin A." Nephron, 60, p. 125-6
  4. Barbara JA, Clarkson AR, LaBrooy J, et al. (1993) "Candida albicans arthritis in a renal allograft recipient with an interaction between cyclosporin and fluconazole." Nephrol Dial Transplant, 8, p. 263-6
  5. (2002) "Product Information. Diflucan (fluconazole)." Roerig Division
  6. Lopez-Gil JA (1993) "Fluconazole-cyclosporin interaction: a dose-dependent effect?" Ann Pharmacother, 27, p. 427-30
  7. Baciewicz AM, Baciewicz FA, Jr (1993) "Ketoconazole and fluconazole drug interactions." Arch Intern Med, 153, p. 1970-6
  8. Assan R, Fredj G, Larger E, Feutren G, Bismuth H (1994) "FK 506/fluconazole interaction enhances FK 506 nephrotoxicity." Diabete Metab, 20, p. 49-52
  9. Osowski CL, Dix SP, Lin LS, Mullins RE, Geller RB, Wingard JR (1996) "Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients." Transplantation, 61, p. 1268-72
  10. Bedford TA, Rowbotham DJ (1996) "Cisapride: drug interactions of clinical significance." Drug Saf, 15, p. 167-75
  11. Sinofsky FE, Pasquale SA (1998) "The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives." Am J Obstet Gynecol, 178, p. 300-4
  12. Nair DR, Morris HH (1999) "Potential fluconazole-induced carbamazepine toxicity." Ann Pharmacother, 33, p. 790-2
  13. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  14. Michalets EL, Williams CR (2000) "Drug interactions with cisapride: clinical implications." Clin Pharmacokinet, 39, p. 49-75
  15. Hilbert J, Messig M, Kuye O, Friedman H (2001) "Evaluation of interaction between fluconazole and an oral contraceptive in healthy women." Obstet Gynecol, 98, p. 218-23
  16. Ulivelli M, Rubegni P, Nuti D, Bartalini S, Giannini F, Rossi S (2004) "Clinical evidence of fluconazole-induced carbamazepine toxicity." J Neurol, 251, p. 622-3
  17. Tsouli S, Maranis S, Kyritsis AP (2011) "Fluconazole-carbamazepine interaction in a patient with bipolar disorder." Psychiatry Clin Neurosci, 65, p. 112
  18. Finch CK, Green CA, Self TH (2002) "Fluconazole-carbamazepine interaction." South Med J, 95, p. 1099-100
View all 18 references

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Epitol (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.