FLUCONAZOLE- fluconazole_tablet

CLINICAL PHARMACOLOGY
The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes. In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. Peak plasma concentrations (C max In fasted normal volunteers, administration of a single oral 400 mg dose of fluconazole leads to a mean C max Administration of a single oral 150 mg tablet of fluconazole to ten lactating women resulted in a mean C max Steady-state concentrations are reached within 5 - 10 days following oral doses of 50 - 400 mg given once daily. Administration of a loading dose (on day 1) of twice the usual daily dose results in plasma concentrations close to steady-state by the second day. The apparent volume of distribution of fluconazole approximates that of total body water. Plasma protein binding is low (11 - 12%). Following either single- or multiple-oral doses for up to 14 days, fluconazole penetrates into all body fluids studied (see table below). In normal volunteers, saliva concentrations of fluconazole were equal to or slightly greater than plasma concentrations regardless of dose, route, or duration of dosing. In patients with bronchiectasis, sputum concentrations of fluconazole following a single 150 mg oral dose were equal to plasma concentrations at both 4 and 24 hours post dose. In patients with fungal meningitis, fluconazole concentrations in the CSF are approximately 80% of the corresponding plasma concentrations. A single oral 150 mg dose of fluconazole administered to 27 patients penetrated into vaginal tissue, resulting in tissue: plasma ratios ranging from 0. 14 over the first 48 hours following dosing. A single oral 150 mg dose of fluconazole administered to 14 patients penetrated into vaginal fluid, resulting in fluid: plasma ratios ranging from 0. 71 over the first 72 hours following dosing. Tissue or Fluid Ratio of Fluconazole Tissue (Fluid) / Plasma Concentration Relative to concurrent concentrations in plasma in subjects with normal renal function. Cerebrospinal fluid Independent of degree of meningeal inflammation. 9 Saliva 1 Sputum 1 Blister Fluid 1 Urine 10 Normal Skin 10 Nails 1 Blister Skin 2 Vaginal Tissue 1 Vaginal Fluid 0. 7 In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose appearing in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites. The pharmacokinetics of fluconazole are markedly affected by reduction in renal function. There is an inverse relationship between the elimination half-life and creatinine clearance. The dose of fluconazole may need to be reduced in patients with impaired renal function. (See DOSAGE AND ADMINISTRATION In normal volunteers, fluconazole administration (doses ranging from 200 mg to 400 mg once daily for up to 14 days) was associated with small and inconsistent effects on testosterone concentrations, endogenous corticosteroid concentrations, and the ACTH-stimulated cortisol response. In children, the following pharmacokinetic data {Mean (%cv)} have been reported: Age Studied Dose (mg/kg) Clearance (mL/min/kg) Half-life (Hours) C max V dss (L/kg) 9 Months-13 years Single-Oral 2 mg/kg 0. 40 (38%) N=14 25. 9 (22%) N=16 ------ 9 Months-13 years Single-Oral 8 mg/kg 0. 51 (60%) N=15 19. 8 (20%) N=15 ------ 5-15 years Multiple IV 2 mg/kg 0. 49 (40%) N=4 17. 5 (25%) N=5 0. 722 (36%) N=4 5-15 years Multiple IV 4 mg/kg 0. 59 (64%) N=5 15. 4 (44%) N=6 0. 729 (33%) N=5 5-15 years Multiple IV 8 mg/kg 0. 66 (31%) N=7 17. 1 (22%) N=8 1. 069 (37%) N=7 Clearance corrected for body weight was not affected by age in these studies. Mean body clearance in adults is reported to be 0. 23 (17%) mL/min/kg. In premature newborns (gestational age 26 to 29 weeks), the mean (%cv) clearance within 36 hours of birth was 0. 180 (35%, N=7) mL/min/kg, which increased with time to a mean of 0. 218 (31%, N=9) mL/min/kg six days later and 0. 333 (56%, N=4) mL/min/kg 12 days later. Similarly, the half-life was 73. 6 hours, which decreased with time to a mean of 53. 2 hours six days later and 46. 6 hours 12 days later. A pharmacokinetic study was conducted in 22 subjects, 65 years of age or older receiving a single 50 mg oral dose of fluconazole. Ten of these patients were concomitantly receiving diuretics. The C max max Oral contraceptives: In a second study, twenty-five normal females received daily doses of both 200 mg fluconazole or placebo for two, ten-day periods. The treatment cycles were one month apart with all subjects receiving fluconazole during one cycle and placebo during the other. The order of study treatment was random. Single doses of an oral contraceptive tablet containing levonorgestrel and ethinyl estradiol were administered on the final treatment day (day 10) of both cycles. Following administration of 200 mg of fluconazole, the mean percentage increase of AUC for levonorgestrel compared to placebo was 25% (range: -12 to 82%) and the mean percentage increase for ethinyl estradiol compared to placebo was 38% (range: -11 to 101%). Both of these increases were statistically significantly different from placebo. A third study evaluated the potential interaction of once weekly dosing of fluconazole 300 mg to 21 normal females taking an oral contraceptive containing ethinyl estradiol and norethindrone. In this placebo-controlled, double-blind, randomized, two-way crossover study carried out over three cycles of oral contraceptive treatment, fluconazole dosing resulted in small increases in the mean AUCs of ethinyl estradiol and norethindrone compared to similar placebo dosing. The mean AUCs of ethinyl estradiol and norethindrone increased by 24% (95% C. range 18 - 31%) and 13% (95% C. range 8 - 18%), respectively relative to placebo. Fluconazole treatment did not cause a decrease in the ethinyl estradiol AUC of any individual subject in this study compared to placebo dosing. The individual AUC values of norethindrone decreased very slightly (<5%) in 3 of the 21 subjects after fluconazole treatment. Cimetidine: max max Antacid: registered Hydrochlorothiazide: max max Rifampin: PRECAUTIONS Warfarin: PRECAUTIONS Phenytoin: PRECAUTIONS Cyclosporine: max max min max min PRECAUTIONS Zidovudine: Theophylline: max max PRECAUTIONS Terfenadine: CONTRAINDICATIONS PRECAUTIONS Oral hypoglycemics: PRECAUTIONS Tolbutamide: max max PRECAUTIONS Glipizide: max max PRECAUTIONS Glyburide: max max PRECAUTIONS Rifabutin: PRECAUTIONS Tacrolimus: PRECAUTIONS Cisapride: max max CONTRAINDICATIONS PRECAUTIONS Midazolam: max max A second randomized, double-dummy, placebo-controlled, cross-over study in three phases was performed to determine the effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. In each phase the subjects were given oral fluconazole 400 mg and intravenous saline; oral placebo and intravenous fluconazole 400 mg; and oral placebo and IV saline. An oral dose of 7. 5 mg of midazolam was ingested after fluconazole/placebo. The AUC and C max max max PRECAUTIONS Azithromycin: Fluconazole is a highly selective inhibitor of fungal cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme functions to convert lanosterol to ergosterol. The subsequent loss of normal sterols correlates with the accumulation of 14-alpha-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Fluconazole has been shown to be active against most strains of the following microorganisms both in vitro Candida albicans Candida glabrata Candida parapsilosis Candida tropicalis Cryptococcus neoformans * In a majority of the studies, fluconazole MIC 90 The following in vitro but their clinical significance is unknown. Fluconazole exhibits in vitro Candida dubliniensis Candida guilliermondii Candida kefyr Candida lusitaniae Candida krusei C. krusei There have been reports of cases of superinfection with Candida C. albicans Candida krusei Cryptococcus neoformans and filamentous fungi: No interpretive criteria have been established for Cryptococcus neoformans Candida species: Broth Dilution Techniques: Candida 1 Diffusion Techniques: Candida 2 Table 1: Susceptibility Interpretive Criteria for Fluconazole Broth Dilution at 48 hours (MIC in mug/mL) Disk Diffusion at 24 hours (Zone Diameters in mm) Antifungal agent Susceptible (S) Intermediate (I) The intermediate category is sometimes called Susceptible-Dose Dependent (SDD) and both categories are equivalent for fluconazole. Resistant (R) Susceptible (S) Intermediate (I) Resistant (R) Fluconazole Isolates of C. krusei <= 8. 0 16-32 >= 64 >= 19 15-18 <= 14 The susceptible category implies that isolates are inhibited by the usually achievable concentrations of antifungal agent tested when the recommended dosage is used. The intermediate category implies that an infection due to the isolate may be appropriately treated in body sites where the drugs are physiologically concentrated or when a high dosage of drug is used. The resistant category implies that isolates are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and clinical efficacy of the agent against the isolate has not been reliably shown in treatment studies. Standardized susceptibility test procedures require the use of quality control organisms to control the technical aspects of the test procedures. Standardized fluconazole powder and 25 mug disks should provide the following range of values noted in Table 1. NOTE: Quality control microorganisms are specific strains of organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within fungi; the specific strains used for microbiological control are not clinically significant. Table 2: Acceptable Quality Control Ranges for Fluconazole to be Used in Validation of Susceptibility Test Results QC Strain Macrodilution (MIC in mug/mL) @ 48 hours Microdilution (MIC in mug/mL) @ 48 hours Disk Diffusion (Zone Diameter in mm) @ 24 hours Candida parapsilosis 2. 0 22-33 Candida krusei 16-64 16-128 --- Quality control ranges have not been established for this strain/antifungal agent combination due to their extensive interlaboratory variation during initial quality control studies. Candida albicans --- --- 28-39 Candida tropicalis --- --- 26-37 Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans Candida albicans. In common with other azole antifungal agents, most fungi show a higher apparent sensitivity to fluconazole in vivo in vitro. Aspergillus flavus Aspergillus fumigatus Blastomyces dermatitidis Coccidioides immitis Histoplasma capsulatum Oral fluconazole has been shown to be active in an animal model of vaginal candidiasis. Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with C. albicans, Cryptococcus neoformans, A. Fluconazole resistance may arise from a modification in the quality or quantity of the target enzyme (lanosterol 14-alpha-demethylase), reduced access to the drug target, or some combination of these mechanisms. Point mutations in the gene (ERG11) ERG11 The second major mechanism of drug resistance involves active efflux of fluconazole out of the cell through the activation of two types of multidrug efflux transporters; the major facilitators (encoded by MDR CDR MDR CDR Resistance in Candida glabrata Candida krusei C. albicans, Candida krusei.
Pharmacokinetics and Metabolism
The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes. In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. Peak plasma concentrations (C max In fasted normal volunteers, administration of a single oral 400 mg dose of fluconazole leads to a mean C max Administration of a single oral 150 mg tablet of fluconazole to ten lactating women resulted in a mean C max Steady-state concentrations are reached within 5 - 10 days following oral doses of 50 - 400 mg given once daily. Administration of a loading dose (on day 1) of twice the usual daily dose results in plasma concentrations close to steady-state by the second day. The apparent volume of distribution of fluconazole approximates that of total body water. Plasma protein binding is low (11 - 12%). Following either single- or multiple-oral doses for up to 14 days, fluconazole penetrates into all body fluids studied (see table below). In normal volunteers, saliva concentrations of fluconazole were equal to or slightly greater than plasma concentrations regardless of dose, route, or duration of dosing. In patients with bronchiectasis, sputum concentrations of fluconazole following a single 150 mg oral dose were equal to plasma concentrations at both 4 and 24 hours post dose. In patients with fungal meningitis, fluconazole concentrations in the CSF are approximately 80% of the corresponding plasma concentrations. A single oral 150 mg dose of fluconazole administered to 27 patients penetrated into vaginal tissue, resulting in tissue: plasma ratios ranging from 0. 14 over the first 48 hours following dosing. A single oral 150 mg dose of fluconazole administered to 14 patients penetrated into vaginal fluid, resulting in fluid: plasma ratios ranging from 0. 71 over the first 72 hours following dosing. Tissue or Fluid Ratio of Fluconazole Tissue (Fluid) / Plasma Concentration Relative to concurrent concentrations in plasma in subjects with normal renal function. Cerebrospinal fluid Independent of degree of meningeal inflammation. 9 Saliva 1 Sputum 1 Blister Fluid 1 Urine 10 Normal Skin 10 Nails 1 Blister Skin 2 Vaginal Tissue 1 Vaginal Fluid 0. 7 In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose appearing in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites. The pharmacokinetics of fluconazole are markedly affected by reduction in renal function. There is an inverse relationship between the elimination half-life and creatinine clearance. The dose of fluconazole may need to be reduced in patients with impaired renal function. (See DOSAGE AND ADMINISTRATION In normal volunteers, fluconazole administration (doses ranging from 200 mg to 400 mg once daily for up to 14 days) was associated with small and inconsistent effects on testosterone concentrations, endogenous corticosteroid concentrations, and the ACTH-stimulated cortisol response. In children, the following pharmacokinetic data {Mean (%cv)} have been reported: Age Studied Dose (mg/kg) Clearance (mL/min/kg) Half-life (Hours) C max V dss (L/kg) 9 Months-13 years Single-Oral 2 mg/kg 0. 40 (38%) N=14 25. 9 (22%) N=16 ------ 9 Months-13 years Single-Oral 8 mg/kg 0. 51 (60%) N=15 19. 8 (20%) N=15 ------ 5-15 years Multiple IV 2 mg/kg 0. 49 (40%) N=4 17. 5 (25%) N=5 0. 722 (36%) N=4 5-15 years Multiple IV 4 mg/kg 0. 59 (64%) N=5 15. 4 (44%) N=6 0. 729 (33%) N=5 5-15 years Multiple IV 8 mg/kg 0. 66 (31%) N=7 17. 1 (22%) N=8 1. 069 (37%) N=7 Clearance corrected for body weight was not affected by age in these studies. Mean body clearance in adults is reported to be 0. 23 (17%) mL/min/kg. In premature newborns (gestational age 26 to 29 weeks), the mean (%cv) clearance within 36 hours of birth was 0. 180 (35%, N=7) mL/min/kg, which increased with time to a mean of 0. 218 (31%, N=9) mL/min/kg six days later and 0. 333 (56%, N=4) mL/min/kg 12 days later. Similarly, the half-life was 73. 6 hours, which decreased with time to a mean of 53. 2 hours six days later and 46. 6 hours 12 days later. A pharmacokinetic study was conducted in 22 subjects, 65 years of age or older receiving a single 50 mg oral dose of fluconazole. Ten of these patients were concomitantly receiving diuretics. The C max max.
Microbiology
Fluconazole is a highly selective inhibitor of fungal cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme functions to convert lanosterol to ergosterol. The subsequent loss of normal sterols correlates with the accumulation of 14-alpha-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Fluconazole has been shown to be active against most strains of the following microorganisms both in vitro Candida albicans Candida glabrata Candida parapsilosis Candida tropicalis Cryptococcus neoformans * In a majority of the studies, fluconazole MIC 90 The following in vitro but their clinical significance is unknown. Fluconazole exhibits in vitro Candida dubliniensis Candida guilliermondii Candida kefyr Candida lusitaniae Candida krusei C. krusei There have been reports of cases of superinfection with Candida C. albicans Candida krusei.
Activity
Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans Candida albicans. In common with other azole antifungal agents, most fungi show a higher apparent sensitivity to fluconazole in vivo in vitro. Aspergillus flavus Aspergillus fumigatus Blastomyces dermatitidis Coccidioides immitis Histoplasma capsulatum Oral fluconazole has been shown to be active in an animal model of vaginal candidiasis. Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with C. albicans, Cryptococcus neoformans, A.fumigatus.
Drug Resistance
Fluconazole resistance may arise from a modification in the quality or quantity of the target enzyme (lanosterol 14-alpha-demethylase), reduced access to the drug target, or some combination of these mechanisms. Point mutations in the gene (ERG11) ERG11 The second major mechanism of drug resistance involves active efflux of fluconazole out of the cell through the activation of two types of multidrug efflux transporters; the major facilitators (encoded by MDR CDR MDR CDR Resistance in Candida glabrata Candida krusei C. krusei There have been reports of cases of superinfection with Candida C. albicans, Candida krusei

INDICATIONS AND USAGE
Fluconazole is indicated for the treatment of: Candida Candida Candida CLINICAL STUDIES Prophylaxis. Fluconazole is also indicated to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy. Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.
What Is Fluconazole?
Fluconazole is a tablet you swallow to treat vaginal yeast infections caused by a yeast called Candida Fluconazole is different from other treatments for vaginal yeast infections because it is a tablet taken by mouth. Fluconazole is also used for other conditions. However, this leaflet is only about using fluconazole for vaginal yeast infections. For information about using fluconazole for other reasons, ask your doctor or pharmacist. See the section of this leaflet for information about vaginal yeast infections.
What Is A Vaginal Yeast Infection?
It is normal for a certain amount of yeast to be found in the vagina. Sometimes too much yeast starts to grow in the vagina and this can cause a yeast infection. Vaginal yeast infections are common. About three out of every four adult women will have at least one vaginal yeast infection during their life. Some medicines and medical conditions can increase your chance of getting a yeast infection. If you are pregnant, have diabetes, use birth control pills, or take antibiotics you may get yeast infections more often than other women. Personal hygiene and certain types of clothing may increase your chances of getting a yeast infection. Ask your doctor for tips on what you can do to help prevent vaginal yeast infections. If you get a vaginal yeast infection, you may have any of the following symptoms:

DOSAGE AND ADMINISTRATION
Vaginal candidiasis: SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL TABLETS AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy. The daily dose of fluconazole for the treatment of infections other than vaginal candidiasis should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse. Oropharyngeal candidiasis: Esophageal candidiasis: Systemic Candida infections: Candida , Urinary tract infections and peritonitis: Candida Cryptococcal meningitis: Prophylaxis in patients undergoing bone marrow transplantation: The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients: Pediatric Patients Adults 3 mg/kg 100 mg 6 mg/kg 200 mg 12 Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. 400 mg Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY Oropharyngeal candidiasis: Esophageal candidiasis: Systemic Candida infections: Candida Cryptococcal meningitis: Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table: Creatinine Clearance (mL/min) Percent of Recommended Dose > 50 100% <= 50 (no dialysis) 50% Regular dialysis 100% after each dialysis These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition. When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults: Weight (kg) x (140-age) 0. 85 x above value Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children: K x linear length or height (cm) (Where K = 0. 55 for children older than 1 year and 0. 45 for infants. ) Fluconazole may be administered orally.
Dosage and Administration in Adults:
Vaginal candidiasis: SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL TABLETS AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy. The daily dose of fluconazole for the treatment of infections other than vaginal candidiasis should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse. Oropharyngeal candidiasis: Esophageal candidiasis: Systemic Candida infections: Candida , Urinary tract infections and peritonitis: Candida Cryptococcal meningitis: Prophylaxis in patients undergoing bone marrow transplantation:.
Dosage and Administration in Children:
The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients: Pediatric Patients Adults 3 mg/kg 100 mg 6 mg/kg 200 mg 12 Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. 400 mg Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY Oropharyngeal candidiasis: Esophageal candidiasis: Systemic Candida infections: Candida Cryptococcal meningitis:
Administration
Fluconazole may be administered orally.
How Should I Take Fluconazole
Take fluconazole by mouth with or without food. You can take fluconazole at any time of the day. Fluconazole keeps working for several days to treat the infection. Generally the symptoms start to go away after 24 hours. However, it may take several days for your symptoms to go away completely. If there is no change in your symptoms after a few days, call your doctor. Directions: Push tablet through foil and take by mouth Just swallow 1 Fluconazole tablet to treat your vaginal yeast infection.

ADVERSE REACTIONS
During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with fluconazole, 150 mg single dose. The overall incidence of side effects possibly related to fluconazole was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience. Sixteen percent of over 4000 patients treated with fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1. 5% of patients due to adverse clinical events and in 1. 3% of patients due to laboratory test abnormalities. Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1. The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving fluconazole for 7 or more days in clinical trials: nausea 3. 7%, headache 1. 9%, skin rash 1. 8%, vomiting 1. 7%, abdominal pain 1. 7%, and diarrhea 1. Hepatobiliary: WARNINGS In two comparative trials evaluating the efficacy of fluconazole for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents. In addition, the following adverse events have occurred during post-marketing experience. Immunologic: Cardiovascular: PRECAUTIONS Central Nervous System: Dermatologic: WARNINGS Hematopoietic and Lymphatic: , Metabolic: Gastrointestinal Other Senses: In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2. 3% of patients due to adverse clinical events and in 1. 4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase. Percentage of Patients With Treatment-Related Side Effects Fluconazole (N=577) Comparative Agents (N=451) With any side effect 13. 3 Vomiting 5. 1 Abdominal pain 2. 6 Diarrhea 2.
In Patients Receiving a Single Dose for Vaginal Candidiasis:
During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with fluconazole, 150 mg single dose. The overall incidence of side effects possibly related to fluconazole was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience.
In Patients Receiving Multiple Doses for Other Infections:
Sixteen percent of over 4000 patients treated with fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities. Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%). The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%. Hepatobiliary: WARNINGS In two comparative trials evaluating the efficacy of fluconazole for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.
Post-Marketing Experience
In addition, the following adverse events have occurred during post-marketing experience. Immunologic: Cardiovascular: PRECAUTIONS Central Nervous System: Dermatologic: WARNINGS Hematopoietic and Lymphatic: , Metabolic: Gastrointestinal Other Senses:
Adverse Reactions in Children:
In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase. Percentage of Patients With Treatment-Related Side Effects Fluconazole (N=577) Comparative Agents (N=451) With any side effect 13.0 9.3 Vomiting 5.4 5.1 Abdominal pain 2.8 1.6 Nausea 2.3 1.6 Diarrhea 2.1 2.2
What Are The Possible Side Effects of Fluconazole?
Like all medicines, fluconazole may cause some side effects that are usually mild to moderate. The most common side effects of fluconazole are: Allergic reactions to fluconazole are rare, but they can be very serious if not treated right away by a doctor. If you cannot reach your doctor, go to the nearest hospital emergency room. Signs of an allergic reaction can include shortness of breath; coughing; wheezing; fever; chills; throbbing of the heart or ears; swelling of the eyelids, face, mouth, neck, or any other part of the body; or skin rash, hives, blisters or skin peeling. Fluconazole has been linked to rare cases of serious liver damage, including deaths, mostly in patients with serious medical problems. Call your doctor if your skin or eyes become yellow, your urine turns a darker color, your stools (bowel movements) are light-colored, or if you vomit or feel like vomiting or if you have severe skin itching. In patients with serious conditions such as AIDS or cancer, rare cases of severe rashes with skin peeling have been reported. Tell your doctor right away if you get a rash while taking fluconazole. Fluconazole may cause other less common side effects besides those listed here. If you develop any side effects that concern you, call your doctor. For a list of all side effects, ask your doctor or pharmacist.

CONTRAINDICATIONS
Fluconazole is contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents. Caution should be used in prescribing fluconazole to patients with hypersensitivity to other azoles. Coadministration of terfenadine is contraindicated in patients receiving fluconazole at multiple doses of 400 mg or higher based upon results of a multiple dose interaction study. Coadministration of cisapride is contraindicated in patients receiving fluconazole. (See CLINICAL PHARMACOLOGY: Drug Interaction Studies PRECAUTIONS
Who Should Not Take Fluconazole?
To avoid a possible serious reaction, do NOT take fluconazole if you are taking cisapride (Propulsid registereddagger

Pediatric Studies
Oropharyngeal candidiasis: Clinical cure at the end of treatment was reported for 86% of fluconazole treated patients compared to 46% of nystatin treated patients. Mycologically, 76% of fluconazole treated patients had the infecting organism eradicated compared to 11% for nystatin treated patients. Fluconazole Nystatin Enrolled 96 90 Clinical Cure 76/88 (86%) 36/78 (46%) Mycological eradication Subjects without follow-up cultures for any reason were considered nonevaluable for mycological response. 55/72 (76%) 6/54 (11%) The proportion of patients with clinical relapse 2 weeks after the end of treatment was 14% for subjects receiving fluconazole and 16% for subjects receiving nystatin. At 4 weeks after the end of treatment the percentages of patients with clinical relapse were 22% for fluconazole and 23% for nystatin.
Pregnancy
Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. There have been reports of multiple congenital abnormalities in infants whose mothers were being treated for 3 or more months with high dose (400-800 mg/day) fluconazole therapy for coccidioidomycosis (an unindicated use). The relationship between fluconazole use and these events is unclear. Fluconazole should be used in pregnancy only if the potential benefit justifies the possible risk to the fetus.
Nursing mothers
Fluconazole is secreted in human milk at concentrations similar to plasma. Therefore, the use of fluconazole in nursing mothers is not recommended.
Pediatric use
An open-label, randomized, controlled trial has shown fluconazole to be effective in the treatment of oropharyngeal candidiasis in children 6 months to 13 years of age. (See CLINICAL STUDIES The use of fluconazole in children with cryptococcal meningitis, Candida Candida CLINICAL PHARMACOLOGY DOSAGE AND ADMINISTRATION In a noncomparative study of children with serious systemic fungal infections, most of which were candidemia, the effectiveness of fluconazole was similar to that reported for the treatment of candidemia in adults. Of 17 subjects with culture-confirmed candidemia, 11 of 14 (79%) with baseline symptoms (3 were asymptomatic) had a clinical cure; 13/15 (87%) of evaluable patients had a mycologic cure at the end of treatment but two of these patients relapsed at 10 and 18 days, respectively, following cessation of therapy. The efficacy of fluconazole 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. The safety profile of fluconazole in children has been studied in 577 children ages 1 day to 17 years who received doses ranging from 1 to 15 mg/kg/day for 1 to 1,616 days. (See ADVERSE REACTIONS Efficacy of fluconazole has not been established in infants less than 6 months of age. (See CLINICAL PHARMACOLOGY
Geriatric use
In non-AIDS patients, side effects possibly related to fluconazole treatment were reported in fewer patients aged 65 and older (9%, n =339) than for younger patients (14%, n=2240). However, there was no consistent difference between the older and younger patients with respect to individual side effects. Of the most frequently reported (>1%) side effects, rash, vomiting and diarrhea occurred in greater proportions of older patients. Similar proportions of older patients (2.4%) and younger patients (1.5%) discontinued fluconazole therapy because of side effects. In post-marketing experience, spontaneous reports of anemia and acute renal failure were more frequent among patients 65 years of age or older than in those between 12 and 65 years of age. Because of the voluntary nature of the reports and the natural increase in the incidence of anemia and renal failure in the elderly, it is however not possible to establish a casual relationship to drug exposure. Controlled clinical trials of fluconazole did not include sufficient numbers of patients aged 65 and older to evaluate whether they respond differently from younger patients in each indication. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Fluconazole is primarily cleared by renal excretion as unchanged drug. Because elderly patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. It may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY DOSAGE AND ADMINISTRATION
Dosage In Patients With Impaired Renal Function:
Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table: Creatinine Clearance (mL/min) Percent of Recommended Dose > 50 100% <= 50 (no dialysis) 50% Regular dialysis 100% after each dialysis These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition. When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults: Weight (kg) x (140-age) 0. 85 x above value Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children: K x linear length or height (cm) (Where K = 0. 55 for children older than 1 year and 0. 45 for infants.

Drug Interaction Studies
Oral contraceptives: In a second study, twenty-five normal females received daily doses of both 200 mg fluconazole or placebo for two, ten-day periods. The treatment cycles were one month apart with all subjects receiving fluconazole during one cycle and placebo during the other. The order of study treatment was random. Single doses of an oral contraceptive tablet containing levonorgestrel and ethinyl estradiol were administered on the final treatment day (day 10) of both cycles. Following administration of 200 mg of fluconazole, the mean percentage increase of AUC for levonorgestrel compared to placebo was 25% (range: -12 to 82%) and the mean percentage increase for ethinyl estradiol compared to placebo was 38% (range: -11 to 101%). Both of these increases were statistically significantly different from placebo. A third study evaluated the potential interaction of once weekly dosing of fluconazole 300 mg to 21 normal females taking an oral contraceptive containing ethinyl estradiol and norethindrone. In this placebo-controlled, double-blind, randomized, two-way crossover study carried out over three cycles of oral contraceptive treatment, fluconazole dosing resulted in small increases in the mean AUCs of ethinyl estradiol and norethindrone compared to similar placebo dosing. The mean AUCs of ethinyl estradiol and norethindrone increased by 24% (95% C.I. range 18 - 31%) and 13% (95% C.I. range 8 - 18%), respectively relative to placebo. Fluconazole treatment did not cause a decrease in the ethinyl estradiol AUC of any individual subject in this study compared to placebo dosing. The individual AUC values of norethindrone decreased very slightly (<5%) in 3 of the 21 subjects after fluconazole treatment. Cimetidine: max max Antacid: registered Hydrochlorothiazide: max max Rifampin: PRECAUTIONS Warfarin: PRECAUTIONS Phenytoin: PRECAUTIONS Cyclosporine: max max min max min PRECAUTIONS Zidovudine: Theophylline: max max PRECAUTIONS Terfenadine: CONTRAINDICATIONS PRECAUTIONS Oral hypoglycemics: PRECAUTIONS Tolbutamide: max max PRECAUTIONS Glipizide: max max PRECAUTIONS Glyburide: max max PRECAUTIONS Rifabutin: PRECAUTIONS Tacrolimus: PRECAUTIONS Cisapride: max max CONTRAINDICATIONS PRECAUTIONS Midazolam: max max A second randomized, double-dummy, placebo-controlled, cross-over study in three phases was performed to determine the effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. In each phase the subjects were given oral fluconazole 400 mg and intravenous saline; oral placebo and intravenous fluconazole 400 mg; and oral placebo and IV saline. An oral dose of 7.5 mg of midazolam was ingested after fluconazole/placebo. The AUC and C max max max PRECAUTIONS Azithromycin:
Drug interactions
(See CLINICAL PHARMACOLOGY: Drug Interaction Studies CONTRAINDICATIONS Oral hypoglycemics Oral hypoglycemics: CLINICAL PHARMACOLOGY: Drug Interaction Studies Coumarin-type anticoagulants: CLINICAL PHARMACOLOGY: Drug Interaction Studies Phenytoin: CLINICAL PHARMACOLOGY: Drug Interaction Studies Cyclosporine: CLINICAL PHARMACOLOGY: Drug Interaction Studies Rifampin: CLINICAL PHARMACOLOGY: Drug Interaction Studies Theophylline: CLINICAL PHARMACOLOGY: Drug Interaction Studies Terfenadine: CONTRAINDICATIONS CLINICAL PHARMACOLOGY: Drug Interaction Studies Cisapride: CONTRAINDICATIONS CLINICAL PHARMACOLOGY: Drug Interaction Studies Astemizole: Rifabutin: CLINICAL PHARMACOLOGY: Drug Interaction Studies Tacrolimus: CLINICAL PHARMACOLOGY: Drug Interaction Studies Short-acting Benzodiazepines: CLINICAL PHARMACOLOGY: Drug Interaction Studies Fluconazole tablets coadministered with ethinyl estradiol- and levonorgestrel-containing oral contraceptives produced an overall mean increase in ethinyl estradiol and levonorgestrel levels; however, in some patients there were decreases up to 47% and 33% of ethinyl estradiol and levonorgestrel levels. (See CLINICAL PHARMACOLOGY: Drug Interaction Studies Physicians should be aware that interaction studies with medications other than those listed in the CLINICAL PHARMACOLOGY

Keep fluconazole and all medicines out of the reach of children.

Susceptibility Testing Methods
Cryptococcus neoformans and filamentous fungi: No interpretive criteria have been established for Cryptococcus neoformans Candida species: Broth Dilution Techniques: Candida 1 Diffusion Techniques: Candida 2 Table 1: Susceptibility Interpretive Criteria for Fluconazole Broth Dilution at 48 hours (MIC in mug/mL) Disk Diffusion at 24 hours (Zone Diameters in mm) Antifungal agent Susceptible (S) Intermediate (I) The intermediate category is sometimes called Susceptible-Dose Dependent (SDD) and both categories are equivalent for fluconazole. Resistant (R) Susceptible (S) Intermediate (I) Resistant (R) Fluconazole Isolates of C. krusei <= 8.0 16-32 >= 64 >= 19 15-18 <= 14 The susceptible category implies that isolates are inhibited by the usually achievable concentrations of antifungal agent tested when the recommended dosage is used. The intermediate category implies that an infection due to the isolate may be appropriately treated in body sites where the drugs are physiologically concentrated or when a high dosage of drug is used. The resistant category implies that isolates are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and clinical efficacy of the agent against the isolate has not been reliably shown in treatment studies.
Quality Control
Standardized susceptibility test procedures require the use of quality control organisms to control the technical aspects of the test procedures. Standardized fluconazole powder and 25 mug disks should provide the following range of values noted in Table 1. NOTE: Quality control microorganisms are specific strains of organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within fungi; the specific strains used for microbiological control are not clinically significant. Table 2: Acceptable Quality Control Ranges for Fluconazole to be Used in Validation of Susceptibility Test Results QC Strain Macrodilution (MIC in mug/mL) @ 48 hours Microdilution (MIC in mug/mL) @ 48 hours Disk Diffusion (Zone Diameter in mm) @ 24 hours Candida parapsilosis 2.0-8.0 1.0-4.0 22-33 Candida krusei 16-64 16-128 --- Quality control ranges have not been established for this strain/antifungal agent combination due to their extensive interlaboratory variation during initial quality control studies. Candida albicans --- --- 28-39 Candida tropicalis --- --- 26-37
CLINICAL STUDIES
Cryptococcal meningitis: 3 et al. Vaginal candidiasis: The therapeutic cure rate, defined as a complete resolution of signs and symptoms of vaginal candidiasis (clinical cure), along with a negative KOH examination and negative culture for Candida Fluconazole PO 150 mg tablet Vaginal Product qhs x 7 days Enrolled 448 422 Evaluable at Late Follow-up 347 (77%) 327 (77%) Clinical cure 239/347 (69%) 235/327 (72%) Mycologic erad. 213/347 (61%) 196/327 (60%) Therapeutic cure 190/347 (55%) 179/327 (55%) Approximately three-fourths of the enrolled patients had acute vaginitis (<4 episodes/12 months) and achieved 80% clinical cure, 67% mycologic eradication and 59% therapeutic cure when treated with a 150 mg fluconazole tablet administered orally. These rates were comparable to control products. The remaining one-fourth of enrolled patients had recurrent vaginitis (>=4 episodes/12 months) and achieved 57% clinical cure, 47% mycologic eradication and 40% therapeutic cure. The numbers are too small to make meaningful clinical or statistical comparisons with vaginal products in the treatment of patients with recurrent vaginitis. Substantially more gastrointestinal events were reported in the fluconazole group compared to the vaginal product group. Most of the events were mild to moderate. Because fluconazole was given as a single dose, no discontinuations occurred. Parameter Fluconazole PO Vaginal Products Evaluable patients 448 422 With any adverse event 141 (31%) 112 (27%) Nervous System 90 (20%) 69 (16%) Gastrointestinal 73 (16%) 18 (4%) With drug-related event 117 (26%) 67 (16%) Nervous System 61 (14%) 29 (7%) Headache 58 (13%) 28 (7%) Gastrointestinal 68 (15%) 13 (3%) Abdominal pain 25 (6%) 7 (2%) Nausea 30 (7%) 3 (1%) Diarrhea 12 (3%) 2 (<1%) Application site event 0 (0%) 19 (5%) Taste Perversion 6 (1%) 0 (0%) Oropharyngeal candidiasis: Clinical cure at the end of treatment was reported for 86% of fluconazole treated patients compared to 46% of nystatin treated patients. Mycologically, 76% of fluconazole treated patients had the infecting organism eradicated compared to 11% for nystatin treated patients. Fluconazole Nystatin Enrolled 96 90 Clinical Cure 76/88 (86%) 36/78 (46%) Mycological eradication Subjects without follow-up cultures for any reason were considered nonevaluable for mycological response. 55/72 (76%) 6/54 (11%) The proportion of patients with clinical relapse 2 weeks after the end of treatment was 14% for subjects receiving fluconazole and 16% for subjects receiving nystatin. At 4 weeks after the end of treatment the percentages of patients with clinical relapse were 22% for fluconazole and 23% for nystatin.
WARNINGS
Hepatic injury: Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of the patient has been observed. Fluconazole hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored for the development of more severe hepatic injury. Fluconazole should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole.
Carcinogenesis,mutagenesis, impairment of fertility
Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.5, 5 or 10 mg/kg/day (approximately 2-7x the recommended human dose). Male rats treated with 5 and 10 mg/kg/day had an increased incidence of hepatocellular adenomas. Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in 4 strains of S. typhimurium in vivo in vitro Fluconazole did not affect the fertility of male or female rats treated orally with daily doses of 5, 10 or 20 mg/kg or with parenteral doses of 5, 25 or 75 mg/kg, although the onset of parturition was slightly delayed at 20 mg/kg PO. In an intravenous perinatal study in rats at 5, 20 and 40 mg/kg, dystocia and prolongation of parturition were observed in a few dams at 20 mg/kg (approximately 5-15x the recommended human dose) and 40 mg/kg, but not at 5 mg/kg. 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. (See CLINICAL PHARMACOLOGY
OVERDOSAGE
There have been reports of overdosage with fluconazole. A 42-year-old patient infected with human immunodeficiency virus developed hallucinations and exhibited paranoid behavior after reportedly ingesting 8200 mg of fluconazole. The patient was admitted to the hospital, and his condition resolved within 48 hours. In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted. Fluconazole is largely excreted in urine. A three-hour hemodialysis session decreases plasma levels by approximately 50%. In mice and rats receiving very high doses of fluconazole, clinical effects in both species included decreased motility and respiration, ptosis, lacrimation, salivation, urinary incontinence, loss of righting reflex and cyanosis; death was sometimes preceded by clonic convulsions.
PATIENT INFORMATION
FLUCONAZOLE TABLETS USP Rx Only This leaflet contains important information about fluconazole. It is not meant to take the place of your doctor’s instructions. Read this information carefully before you take fluconazole. Ask your doctor or pharmacist if you do not understand any of this information or if you want to know more about fluconazole. Fluconazole is a tablet you swallow to treat vaginal yeast infections caused by a yeast called Candida Fluconazole is different from other treatments for vaginal yeast infections because it is a tablet taken by mouth. Fluconazole is also used for other conditions. However, this leaflet is only about using fluconazole for vaginal yeast infections. For information about using fluconazole for other reasons, ask your doctor or pharmacist. See the section of this leaflet for information about vaginal yeast infections. It is normal for a certain amount of yeast to be found in the vagina. Sometimes too much yeast starts to grow in the vagina and this can cause a yeast infection. Vaginal yeast infections are common. About three out of every four adult women will have at least one vaginal yeast infection during their life. Some medicines and medical conditions can increase your chance of getting a yeast infection. If you are pregnant, have diabetes, use birth control pills, or take antibiotics you may get yeast infections more often than other women. Personal hygiene and certain types of clothing may increase your chances of getting a yeast infection. Ask your doctor for tips on what you can do to help prevent vaginal yeast infections. If you get a vaginal yeast infection, you may have any of the following symptoms: Do not take fluconazole if you take certain medicines. They can cause serious problems. Therefore, tell your doctor about all the medicines you take including: registereddagger registereddouble dagger To avoid a possible serious reaction, do NOT take fluconazole if you are taking cisapride (Propulsid registereddagger Take fluconazole by mouth with or without food. You can take fluconazole at any time of the day. Fluconazole keeps working for several days to treat the infection. Generally the symptoms start to go away after 24 hours. However, it may take several days for your symptoms to go away completely. If there is no change in your symptoms after a few days, call your doctor. Directions: Push tablet through foil and take by mouth Just swallow 1 Fluconazole tablet to treat your vaginal yeast infection. Graphic Some medicines can affect how well fluconazole works. Check with your doctor before starting any new medicines within seven days of taking fluconazole. Like all medicines, fluconazole may cause some side effects that are usually mild to moderate. The most common side effects of fluconazole are: Allergic reactions to fluconazole are rare, but they can be very serious if not treated right away by a doctor. If you cannot reach your doctor, go to the nearest hospital emergency room. Signs of an allergic reaction can include shortness of breath; coughing; wheezing; fever; chills; throbbing of the heart or ears; swelling of the eyelids, face, mouth, neck, or any other part of the body; or skin rash, hives, blisters or skin peeling. Fluconazole has been linked to rare cases of serious liver damage, including deaths, mostly in patients with serious medical problems. Call your doctor if your skin or eyes become yellow, your urine turns a darker color, your stools (bowel movements) are light-colored, or if you vomit or feel like vomiting or if you have severe skin itching. In patients with serious conditions such as AIDS or cancer, rare cases of severe rashes with skin peeling have been reported. Tell your doctor right away if you get a rash while taking fluconazole. Fluconazole may cause other less common side effects besides those listed here. If you develop any side effects that concern you, call your doctor. For a list of all side effects, ask your doctor or pharmacist. In case of an accidental overdose, call your doctor right away or go to the nearest emergency room. Keep fluconazole and all medicines out of the reach of children. Medicines are sometimes prescribed for conditions that are mentioned in patient information leaflets. Do not use fluconazole for a condition for which it was not prescribed. Do not give fluconazole to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about fluconazole. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about fluconazole that is written for health professionals. dagger double dagger Manufactured by: Glenmark Generics Ltd. Manufactured for: Glenmark Generics Inc. , USA Questions? 1 (888)721-7115 www. glenmarkgenerics. com May 2010 Repackaged by: Glenmark Logo.

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