Coumarin-type anticoagulants: In an interaction study, fluconazole increased the prothrombin time (12%) following warfarin administration in healthy male volunteers. Therefore, careful monitoring of prothrombin time in patients receiving fluconazole and coumarin-type anticoagulants is recommended.
Oral Sulfonylureas: There have been reports that an interaction exists when fluconazole is administered concomitantly with oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide), leading to prolonged serum half-life. Fluconazole and oral sulfonylureas may be co-administered to diabetic patients, but the possibility of a hypoglycaemic episode should be borne in mind.
Hydrochlorothiazide: In a kinetic interaction study, concomitant administration of fluconazole and hydrochlorothiazide increased plasma concentrations of fluconazole by 40%. It is not necessary to change the fluconazole dose regimen in subjects receiving concomitant diuretics, although the prescriber should bear it in mind.
Phenytoin: Fluconazole increases the plasma concentrations of phenytoin. If it is necessary to administer both drugs concomitantly, phenytoin concentrations should be monitored and the phenytoin dose adjusted to maintain therapeutic levels.
Oral Contraceptives: Multiple dose use of fluconazole is unlikely to have an effect on the efficacy of the combined oral contraceptive.
Rifampicin: Rifampicin enhances the metabolism of concurrently administered fluconazole (25% decrease in the AUC and 20% shorter half-life of fluconazole). An increase of the fluconazole dose should be considered in patients receiving concomitant rifampicin.
Cyclosporin: Fluconazole may significantly increase cyclosporin levels in renal transplant patients with or without renal impairment. Careful monitoring of cyclosporin concentrations and serum creatinine is recommended in patients receiving fluconazole and cyclosporin.
Theophylline: Fluconazole may decrease the clearance rate of theophylline.
Rifabutin: Concomitant administration of fluconazole and rifabutin may increase the serum levels of rifabutin. Careful monitoring of rifabutin serum levels is recommended in patients taking fluconazole and rifabutin.
Tacrolimus: Concomitant administration of fluconazole and tacrolimus may increase the serum levels of tacrolimus. There have been reports of nephrotoxicity in patients to whom fluconazole and tacrolimus were co-administered. Careful monitoring of tacrolimus serum concentrations is recommended in patients receiving fluconazole and tacrolimus concomitantly.
Zidovudine: Concomitant administration with fluconazole shows increased levels of zidovudine most likely caused by the decreased conversion of zidovudine to its major metabolite. Patients receiving fluconazole and zidovudine concomitantly should be carefully monitored for the development of zidovudine-related adverse reactions.
Benzodiazepines: (Short acting) After oral administration of midazolam, fluconazole resulted in substantial increases in midazolam levels and psychomotor effects. Consideration should be given to decreasing the benzodiazepine dosage and the patients should be appropriately monitored if concomitant benzodiazepine therapy is necessary in patients receiving fluconazole.
Azithromycin: There is no significant pharmacokinetic interaction between fluconazole and azithromycin.
Cisapride: There have been reports of cardiac events, including torsades de pointes, in patients to whom fluconazole and cisapride were co-administered. Cisapride increases the risk of ventricular arrhythmia troubles, notably torsades de pointes. A controlled study found that concomitant fluconazole 200mg once daily and cisapride 20 mg 4 times a day yielded a significant increase in cisapride plasma levels and prolongation of QTc interval. Co-administration of cisapride is contraindicated in patients receiving fluconazole.
Pimozide: Combination with fluconazole will increase risk of ventricular arrhythmia troubles, notably torsades de pointes.
Terfenadine: Serious cardiac dysrhythmias secondary to prolongation of QTc intervals in patients receiving azole antifungals in conjunction with terfenadine. The combined use of fluconazole at doses ≥ 400mg with terfenadine is contraindicated. The Coadministration of fluconazole at doses <400mg/day with terfenadine should be carefully monitored.
Others: There have been reports that when oral fluconazole is co-administered with food, cimetidine, antacids or following total body irradiation for bone marrow transplantation, no clinically significant impairment of fluconazole absorption occurs.
Concomitant administration of fluconazole and astemizole or other drugs metabolised by the cytochrome P450 system may be associated with elevations in serum concentrations of these drugs. Therefore, caution should be used when co-administering fluconazole.