Skip to main content

Drug Interactions between carbamazepine and itraconazole

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

carBAMazepine itraconazole

Applies to: carbamazepine and itraconazole

GENERALLY AVOID: Coadministration with carbamazepine may significantly decrease the oral bioavailability and plasma concentrations of itraconazole and ketoconazole. In vitro studies have shown that CYP450 3A4 is the major enzyme involved in the metabolism of these azole antifungal agents, and carbamazepine is a known potent inducer as well as substrate of the enzyme. Treatment failure associated with substantially reduced and possibly subtherapeutic plasma concentrations of itraconazole has been reported during concurrent therapy with carbamazepine. Conversely, both itraconazole and ketoconazole are potent inhibitors of CYP450 3A4 and may increase the plasma levels of carbamazepine by inhibiting its metabolism. In a pharmacokinetic study involving eight patients with epilepsy stabilized on carbamazepine therapy, plasma concentrations of carbamazepine increased by an average of 29% following administration of ketoconazole (200 mg/day orally for 10 days) and returned to baseline following discontinuation of ketoconazole.

MANAGEMENT: Concomitant use of itraconazole or ketoconazole with carbamazepine should generally be avoided. Some authorities recommend avoiding coadministration of potent CYP450 3A4 inducers such as carbamazepine from 2 weeks before and during treatment with these azole antifungal agents unless the benefits outweigh the risk of potentially reduced antifungal efficacy. In addition, some recommend avoiding carbamazepine from 2 weeks before, during, and for 2 weeks after treatment with itraconazole. If coadministration is required, patients should be monitored for carbamazepine toxicity as well as antifungal treatment failure, and the dosage of each medication adjusted as necessary. Alternatively, other antifungal agents that are less likely to interact with carbamazepine may be considered if clinically appropriate (e.g., terbinafine or fluconazole). Patients should be advised to seek medical attention if they develop potential signs and symptoms of carbamazepine toxicity such as headache, nausea, dizziness, slurred speech, nystagmus, visual disturbances, tremor, and ataxia.

References (6)
  1. Tucker RM, Denning DW, Hanson LH, et al. (1992) "Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations." Clin Infect Dis, 14, p. 165-74
  2. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  3. Schaferkorting M (1993) "Pharmacokinetic optimisation of oral antifungal therapy." Clin Pharmacokinet, 25, p. 329-41
  4. Spina E, Arena D, Scordo MG, Fazio A, Pisani F, Perucca E (1997) "Elevation of plasma carbamazepine concentrations by ketoconazole in patients with epilepsy." Ther Drug Monit, 19, p. 535-8
  5. Albengres E, Le Louet H, Tillement JP (1998) "Systemic antifungal agents. Drug interactions of clinical significance." Drug Saf, 18, p. 83-97
  6. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Moderate

carBAMazepine food

Applies to: 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 (3)
  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
Moderate

itraconazole food

Applies to: itraconazole

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

References (10)
  1. Van Peer A, Woestenborghs R, Heykants J, et al. (1989) "The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects." Eur J Clin Pharmacol, 36, p. 423-6
  2. Wishart JM (1987) "The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection." J Am Acad Dermatol, 17, p. 220-3
  3. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  4. Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, Van de Velde V (1993) "Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers." Antimicrob Agents Chemother, 37, p. 778-84
  5. Zimmermann T, Yeates RA, Albrecht M, Laufen H, Wildfeuer A (1994) "Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in japanese subjects." Int J Clin Pharmacol Res, 14, p. 87-93
  6. (2022) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  7. Kawakami M, Suzuki K, Ishizuka T, Hidaka T, Matsuki Y, Nakamura H (1998) "Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects." Int J Clin Pharmacol Ther, 36, p. 306-8
  8. Barone JA, Moskotitz BL, Guarnieri J, Hassell AE, Colaizzi JL, Bierman RH, Jessen L (1998) "Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers." Pharmacotherapy, 18, p. 295-301
  9. Penzak SR, Gubbins PO, Gurley BJ, Wang PL, Saccente M (1999) "Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers." Ther Drug Monit, 21, p. 304-9
  10. Katz HI (1999) "Drug interactions of the newer oral antifungal agents." Br J Dermatol, 141, p. 26-32

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer