Carbamazepine; Hydantoins/Selected Azole Antifungals
Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.
How the interaction occurs:
Fluconazole, itraconazole, and ketoconazole may slow down how quickly your liver processes your seizure medicine.Your seizure medicine may speed up how quickly your liver processes itraconazole and ketoconazole.
What might happen:
If you take fluconazole, itraconazole, or ketoconazole with your seizure medicine, the amount of seizure medicine in your blood may increase and may cause toxic side effects such as drowsiness, dizziness, blurred or double vision, or loss of coordination.If you take your seizure medicine with your itraconazole or ketoconazole, the amount of itraconazole or ketoconazole in your blood may decrease and it may not work as well.
What you should do about this interaction:
Make sure your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together.If you are taking fluconazole, itraconazole or ketoconazole, your doctor may want to check the amount of seizure medicine in your blood during and after treatment with your antifungal medicine. Your doctor may need to change the dose of your seizure medicine during and after your treatment with fluconazole, itraconazole, or ketoconazole. Let your doctor know right away if you have any symptoms of seizure medicine toxicity.If you are taking itraconazole or ketoconazole, let your doctor know if your condition does not improve or worsens. Your doctor may need to change your antifungal medicine.If you are unsure which antifungal agent you are taking, ask your healthcare professional.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.
1.Ulivelli M, Rubegni P, Nuti D, Bartalini S, Giannini F, Rossi S. Clinical evidence of fluconazole-induced carbamazepine toxicity. J Neurol 2004 May; 251(5):622-3.
2.Nair DR, Morris HH. Potential fluconazole-induced carbamazepine toxicity. Ann Pharmacother 1999 Jul-Aug;33(7-8):790-2.
3.Finch CK, Green CA, Self TH. Fluconazole-carbamazepine interaction. South Med J 2002 Sep;95(9):1099-100.
4.Sporanox (itraconazole) US prescribing information. Janssen Pharmaceutica Products, L.P. April, 2012.
5.Nizoral (ketoconazole oral) US prescribing information. Janssen Pharmaceuticals February, 2014.
6.Spina E, Arena D, Scordo MG, Fazio A, Pisani F, Perucca E. Elevation of plasma carbamazepine concentrations by ketoconazole in patients with epilepsy. Ther Drug Monit 1997 Oct;19(5):535-8.
7.Pirmohamed M, Kitteringham NR, Guenthner TM, Breckenridge AM, Park BK. An investigation of the formation of cytotoxic, protein-reactive and stable metabolites from carbamazepine in vitro. Biochem Pharmacol 1992 Apr 15; 43(8):1675-82.
8.Pearce RE, Vakkalagadda GR, Leeder JS. Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites. Drug Metab Dispos 2002 Nov;30(11):1170-9.
9.Blum RA, Wilton JH, Hilligoss DM, Gardner MJ, Henry EB, Harrison NJ, Schentag JJ. Effect of fluconazole on the disposition of phenytoin. Clin Pharmacol Ther 1991 Apr;49(4):420-5.
10.Touchette MA, Chandrasekar PH, Milad MA, Edwards DJ. Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man. Br J Clin Pharmacol 1992 Jul;34(1):75-8.
11.Ducharme MP, Slaughter RL, Warbasse LH, Chandrasekar PH, Van de Velde V, Mannens G, Edwards DJ. Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin. Clin Pharmacol Ther 1995 Dec;58(6):617-24.
12.Mitchell AS, Holland JT. Fluconazole and phenytoin: a predictable interaction. BMJ 1989 May 13;298(6683):1315.
13.Howitt KM, Oziemski MA. Phenytoin toxicity induced by fluconazole. Med J Aust 1989 Nov 20;151(10):603-4.
14.Bonay M, Jonville-Bera AP, Diot P, Lemarie E, Lavandier M, Autret E. Possible interaction between phenobarbital, carbamazepine and itraconazole. Drug Saf 1993 Oct;9(4):309-11.
15.Tucker RM, Denning DW, Hanson LH, Rinaldi MG, Graybill JR, Sharkey PK, Pappagianis D, Stevens DA. Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations. Clin Infect Dis 1992 Jan;14(1):165-74.
16.Diflucan (fluconazole) US prescribing information. Pfizer Inc. September, 2013.
17.Tsouli S, Maranis S, Kyritsis AP. Fluconazole-carbamazepine interaction in a patient with bipolar disorder. Psychiatry Clin Neurosci 2011 Feb; 65(1):112.