Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. Frequent monitoring for adverse events is recommended. Half of the celecoxib dose may be necessary when combined with fluconazole. Cyclophosphamide Combination therapy with cyclophosphamide and fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine.

Fentanyl One fatal case of possible fentanyl fluconazole interaction was reported. The author judged that the patient died from fentanyl intoxication. Furthermore, in a randomized crossover study with 12 healthy volunteers it was shown that fluconazole delayed the elimination of fentanyl significantly. Elevated fentanyl concentration may lead to respiratory depression.

Halofantrine Fluconazole can increase halofantrine plasma concentration due to an inhibitory effect on CYP3A4. If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored. Losartan Fluconazole inhibits the metabolism of losartan to its active metabolite E 74 which is responsible for most of the angiotensin Il-receptor antagonism which occurs during treatment with losartan. Patients should have their blood pressure monitored continuously.

Methadone Fluconazole may enhance the serum concentration of methadone. Dosage adjustment of methadone may be necessary. Prednisone There was a case report that a liver-transplanted patient treated with prednisone developed acute adrenal cortex insufficiency when a three month therapy with fluconazole was discontinued. The discontinuation of fluconazole presumably caused an enhanced CYP3A4 activity which led to increased metabolism of prednisone.

Patients on long-term treatment with fluconazole and prednisone should be carefully monitored for adrenal cortex insufficiency when fluconazole is discontinued. Dosage adjustment of saquinavir may be necessary. Sirolimus Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein.

Vinca Alkaloids Although not studied, fluconazole may increase the plasma levels of the vinca alkaloids e. Vitamin A Based on a case report in one patient receiving combination therapy with all-trans-retinoid acid an acid form of vitamin A and fluconazole, CNS related undesirable effects have developed in the form of pseudotumour cerebri, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS related undesirable effects should be borne in mind.

Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions. Dosage reduction of zidovudine may be considered. Carcinogenesis, Mutagenesis, and Impairment of Fertility Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.

Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in 4 strains of S. The disturbances in parturition were reflected by a slight increase in the number of still born pups and decrease of neonatal survival at these dose levels.

The effects on parturition in rats are consistent with the species specific estrogen-lowering property produced by high doses of fluconazole. Such a hormone change has not been observed in women treated with fluconazole. Pregnancy Pregnancy Category C Single mg tablet use for Vaginal Candidiasis There are no adequate and well-controlled studies of Diflucan in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of mg.

These reported anomalies are similar to those seen in animal studies. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. Human Data Several published epidemiologic studies do not suggest an increased risk of congenital anomalies associated with low dose exposure to fluconazole in pregnancy most subjects received a single oral dose of mg.

The features seen in these infants include: These effects are similar to those seen in animal studies. Maternal weight gain was impaired at all dose levels approximately 0. These effects are consistent with the inhibition of estrogen synthesis in rats and may be a result of known effects of lowered estrogen on pregnancy, organogenesis, and parturition Nursing Mothers Fluconazole is secreted in human milk at concentrations similar to maternal plasma concentrations.

Caution should be exercised when Diflucan is administered to a nursing woman. Pediatric Use An open-label, randomized, controlled trial has shown Diflucan to be effective in the treatment of oropharyngeal candidiasis in children 6 months to 13 years of age. The use of Diflucan in children with cryptococcal meningitis, Candida esophagitis, or systemic Candida infections is supported by the efficacy shown for these indications in adults and by the results from several small noncomparative pediatric clinical studies.

In a noncomparative study of children with serious systemic fungal infections, most of which were candidemia, the effectiveness of Diflucan was similar to that reported for the treatment of candidemia in adults. The efficacy of Diflucan for the suppression of cryptococcal meningitis was successful in 4 of 5 children treated in a compassionate-use study of fluconazole for the treatment of life-threatening or serious mycosis. There is no information regarding the efficacy of fluconazole for primary treatment of cryptococcal meningitis in children.

Efficacy of Diflucan has not been established in infants less than 6 months of age. A small number of patients 29 ranging in age from 1 day to 6 months have been treated safely with Diflucan. The absolute magnitude of this interaction is unknown because of the intrinsically nonlinear disposition of phenytoin. Cyclosporine Cyclosporine AUC and Cmax were determined before and after the administration of fluconazole mg daily for 14 days in eight renal transplant patients who had been on cyclosporine therapy for at least 6 months and on a stable cyclosporine dose for at least 6 weeks.

There was a significant increase in cyclosporine AUC, Cmax, Cmin hour concentration , and a significant reduction in apparent oral clearance following the administration of fluconazole. Zidovudine Plasma zidovudine concentrations were determined on two occasions before and following fluconazole mg daily for 15 days in 13 volunteers with AIDS or ARC who were on a stable zidovudine dose for at least two weeks.

There was a significant increase in zidovudine AUC following the administration of fluconazole. The metabolite, GZDV, to parent drug ratio significantly decreased after the administration of fluconazole, from 7. There were significant increases in theophylline AUC, Cmax, and half-life with a corresponding decrease in clearance.

The half-life of theophylline increased from 6. Terfenadine Six healthy volunteers received terfenadine 60 mg BID for 15 days. Fluconazole mg was administered daily from days 9 through Fluconazole did not affect terfenadine plasma concentrations. There was no change in cardiac repolarization as measured by Holter QTc intervals.

Another study at a mg and mg daily dose of fluconazole demonstrated that fluconazole taken in doses of mg per day or greater significantly increases plasma levels of terfenadine when taken concomitantly. Oral Hypoglycemics The effects of fluconazole on the pharmacokinetics of the sulfonylurea oral hypoglycemic agents tolbutamide, glipizide, and glyburide were evaluated in three placebo-controlled studies in normal volunteers.

All subjects received the sulfonylurea alone as a single dose and again as a single dose following the administration of fluconazole mg daily for 7 days. Tolbutamide In 13 normal male volunteers, there was significant increase in tolbutamide mg single dose AUC and Cmax following the administration of fluconazole.

Glyburide The AUC and Cmax of glyburide 5 mg single dose were significantly increased following the administration of fluconazole in 20 normal male volunteers. Five subjects required oral glucose following the ingestion of glyburide after 7 days of fluconazole administration. Rifabutin There have been published reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin.

Tacrolimus There have been published reports that an interaction exists when fluconazole is administered concomitantly with tacrolimus, leading to increased serum levels of tacrolimus.

Cisapride A placebo-controlled, randomized, multiple-dose study examined the potential interaction of fluconazole with cisapride. Two groups of 10 normal subjects were administered fluconazole tablets mg daily or placebo.

Cisapride 20 mg four times daily was started after 7 days of fluconazole or placebo dosing. Fluconazole significantly increased the QTc interval in subjects receiving cisapride 20 mg four times daily for 5 days.

Midazolam The effect of fluconazole on the pharmacokinetics and pharmacodynamics of midazolam was examined in a randomized, cross-over study in 12 volunteers. In the study, subjects ingested placebo or mg fluconazole on Day 1 followed by mg daily from Day 2 to Day 6.

In addition, a 7. The psychomotor effects of midazolam were significantly increased after oral administration of midazolam but not significantly affected following intravenous midazolam. Although not studied in vitro or in vivo, concomitant administration of Fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsades de pointes.

Coadministration of Fluconazole and quinidine is contraindicated. An effect of this magnitude should not necessitate a change in the Fluconazole dose regimen in subjects receiving concomitant diuretics. Dosage adjustment of alfentanil may be necessary. Fluconazole increases the effect of amitriptyline and nortriptyline. Concurrent administration of Fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: The clinical significance of results obtained in these studies is unknown.

An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single mg oral dose of azithromycin on the pharmacokinetics of a single mg oral dose of Fluconazole as well as the effects of Fluconazole on the pharmacokinetics of azithromycin.

There was no significant pharmacokinetic interaction between Fluconazole and azithromycin. There is a risk of developing carbamazepine toxicity. Certain calcium channel antagonists nifedipine, isradipine, amlodipine, verapamil, and felodipine are metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists.

Frequent monitoring for adverse events is recommended. Half of the celecoxib dose may be necessary when combined with Fluconazole. Combination therapy with cyclophosphamide and Fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine.

One fatal case of possible fentanyl Fluconazole interaction was reported. The author judged that the patient died from fentanyl intoxication. Furthermore, in a randomized crossover study with 12 healthy volunteers it was shown that Fluconazole delayed the elimination of fentanyl significantly.

Elevated fentanyl concentration may lead to respiratory depression. Fluconazole can increase halofantrine plasma concentration due to an inhibitory effect on CYP3A4. If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored.

Fluconazole inhibits the metabolism of losartan to its active metabolite E 74 which is responsible for most of the angiotensin Il-receptor antagonism which occurs during treatment with losartan. Patients should have their blood pressure monitored continuously.

Fluconazole may enhance the serum concentration of methadone. Dosage adjustment of methadone may be necessary. There was a case report that a liver-transplanted patient treated with prednisone developed acute adrenal cortex insufficiency when a three month therapy with Fluconazole was discontinued.

The discontinuation of Fluconazole presumably caused an enhanced CYP3A4 activity which led to increased metabolism of prednisone. Patients on long-term treatment with Fluconazole and prednisone should be carefully monitored for adrenal cortex insufficiency when Fluconazole is discontinued. Dosage adjustment of saquinavir may be necessary. Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein. Although not studied, Fluconazole may increase the plasma levels of the vinca alkaloids e.

Based on a case report in one patient receiving combination therapy with all-transretinoid acid an acid form of vitamin A and Fluconazole, CNS related undesirable effects have developed in the form of pseudotumour cerebri, which disappeared after discontinuation of Fluconazole treatment.

This combination may be used but the incidence of CNS related undesirable effects should be borne in mind. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions. Dosage reduction of zidovudine may be considered. Carcinogenesis, Mutagenesis and Impairment of Fertility Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2. Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in 4 strains of S.

The disturbances in parturition were reflected by a slight increase in the number of still born pups and decrease of neonatal survival at these dose levels. The effects on parturition in rats are consistent with the species specific estrogen-lowering property produced by high doses of Fluconazole. Such a hormone change has not been observed in women treated with Fluconazole. Single mg tablet use for Vaginal Candidiasis: There are no adequate and well-controlled studies of Fluconazole in pregnant women.

Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of mg. These reported anomalies are similar to those seen in animal studies. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. See WARNINGS, Use in Pregnancy Human Data Several published epidemiologic studies do not suggest an increased risk of congenital anomalies associated with low dose exposure to Fluconazole in pregnancy most subjects received a single oral dose of mg.

DESCRIPTION

Other reported clinical experience has not identified differences in responses between the elderly diflucan younger patients. Short-acting Benzodiazepines Following diflucan administration of midazolam, fluconazole resulted in days increases in midazolam concentrations and psychomotor effects, diflucan 100mg for 7 days. There was a significant increase in zidovudine AUC following the administration of fluconazole, diflucan 100mg for 7 days. Dose adjustment of warfarin may be necessary. This effect on midazolam appears to be more pronounced following oral administration of Fluconazole than with Fluconazole administered intravenously. Cyclophosphamide Combination therapy with cyclophosphamide and fluconazole results in an increase in serum bilirubin and serum creatinine. Patients on days treatment with fluconazole and prednisone should be days monitored for adrenal for insufficiency 100mg fluconazole is discontinued. This combination may be used but the incidence of CNS related undesirable effects should be borne in mind. Vaginal candidiasis vaginal yeast infections due for Candida. The clinical significance 100mg results obtained in these studies is unknown. Oral Contraceptives Two pharmacokinetic studies with a combined oral contraceptive have been performed using multiple doses 100mg fluconazole. Another study at a mg and mg daily dose of fluconazole demonstrated that fluconazole taken in doses of mg per day or greater significantly increases plasma levels of terfenadine when diflucan concomitantly.

How Long Does It Take Fluconazole To Work?

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