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Fluconazole
Overview
What is Fluconazole?
Fluconazole USP, the first of a new subclass of synthetic triazole antifungal agents, is available as tablets for oral administration.
Fluconazole USP is designated chemically as 2,4-difluoro-α,α-bis(1H-1,2,4-triazol-1-ylmethyl) benzyl alcohol with an empirical formula of CHFNO and molecular weight 306.3. The structural formula is:
Fluconazole USP is a white crystalline solid which is slightly soluble in water and saline.
Fluconazole tablets USP contain 50, 100, 150, or 200 mg of fluconazole USP and the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, FD&C Red No. 40 aluminum lake dye, magnesium stearate, microcrystalline cellulose and povidone.
What does Fluconazole look like?
What are the available doses of Fluconazole?
Sorry No records found.
What should I talk to my health care provider before I take Fluconazole?
Sorry No records found
How should I use Fluconazole?
Fluconazole is indicated for the treatment of:
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 interacts with Fluconazole?
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 and
What are the warnings of Fluconazole?
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.
- Anaphylaxis: In rare cases, anaphylaxis has been reported.
- Dermatologic: Patients have rarely developed exfoliative skin disorders during treatment with fluconazole. In patients with serious underlying diseases (predominantly AIDS and malignancy), these have rarely resulted in a fatal outcome. Patients who develop rashes during treatment with fluconazole should be monitored closely and the drug discontinued if lesions progress.
What are the precautions of Fluconazole?
General
Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been rare cases of QT prolongation and torsade de pointes in patients taking fluconazole. Most of these reports involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant medications that may have been contributory.
Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions.
The convenience and efficacy of the single dose oral tablet of fluconazole regimen for the treatment of vaginal yeast infections should be weighed against the acceptability of a higher incidence of drug related adverse events with fluconazole (26%) versus intravaginal agents (16%) in U.S. comparative clinical studies. (See and
Drug interactions
(Seeand Clinically or potentially significant drug interactions between fluconazole and the following agents/classes have been observed. These are described in greater detail below:
Oral hypoglycemicsCoumarin-type anticoagulantsPhenytoinCyclosporineRifampinTheophyllineTerfenadineCisaprideAstemizoleRifabutinTacrolimusShort-term benzodiazepines
Oral hypoglycemics:
Coumarin-type anticoagulants:
Phenytoin:
Cyclosporine:
Rifampin:
Theophylline:
Terfenadine:
Cisapride:
Astemizole:
Rifabutin:
Tacrolimus:
Short-acting Benzodiazepines:
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 .) The data presently available indicate that the decreases in some individual ethinyl estradiol and levonorgestrel AUC values with fluconazole treatment are likely the result of random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol and levonorgestrel, there is no evidence that fluconazole is a net inducer of ethinyl estradiol or levonorgestrel metabolism. The clinical significance of these effects is presently unknown.
Physicians should be aware that interaction studies with medications other than those listed in the section have not been conducted, but such interactions may occur.
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 , and in the mouse lymphoma L5178Y system. Cytogenetic studies (murine bone marrow cells, following oral administration of fluconazole) and (human lymphocytes exposed to fluconazole at 1000 μg/mL) showed no evidence of chromosomal mutations.
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 )
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
The use of fluconazole in children with cryptococcal meningitis, esophagitis, or systemic infections is supported by the efficacy shown for these indications in adults and by the results from several small noncomparative pediatric clinical studies. In addition, pharmacokinetic studies in children (see ) have established a dose proportionality between children and adults. (See )
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
Efficacy of fluconazole has not been established in infants less than 6 months of age. (See A small number of patients (29) ranging in age from 1 day to 6 months have been treated safely with fluconazole.
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 and )
What are the side effects of Fluconazole?
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:
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:
Central Nervous System:
Dermatologic:
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.
| (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 should I look out for while using Fluconazole?
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 and
What might happen if I take too much Fluconazole?
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.
How should I store and handle Fluconazole?
Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000Fluconazole Tablets USP: Pink trapezoidal tablets containing 50, 100 or 200 mg of fluconazole USP are packaged in bottles. The 150 mg fluconazole tablets are pink, oval shaped, packaged in a blister card of 1 tablet. Fluconazole Tablets USP are supplied as follows: Fluconazole Tablets USP 50 mg: Engraved with “50” on one side and plain on the other side. NDC 68462-101-30 Bottles of 30NDC 68462-101-10 Bottles of 1000 Fluconazole Tablets USP 100 mg: Engraved with “100” on one side and plain on the other side.NDC 68462-102-30 Bottles of 30NDC 68462-102-10 Bottles of 1000 Fluconazole Tablets USP 150 mg: Engraved with “150” on one side and plain on the other side.NDC 68462-103-40 Carton of 12 blister cards of 1 tablet Fluconazole Tablets USP 200 mg: Engraved with “200” on one side and plain on the other side.NDC 68462-104-30 Bottles of 30NDC 68462-104-10 Bottles of 1000
Clinical Information
Chemical Structure
No Image foundClinical 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) in fasted normal volunteers occur between 1 and 2 hours with a terminal plasma elimination half-life of approximately 30 hours (range: 20 - 50 hours) after oral administration.
In fasted normal volunteers, administration of a single oral 400 mg dose of fluconazole leads to a mean C of 6.72 μg/mL (range: 4.12 to 8.08 μg/mL) and after single oral doses of 50 - 400 mg, fluconazole plasma concentrations and AUC (area under the plasma concentration-time curve) are dose proportional.
Administration of a single oral 150 mg tablet of fluconazole to ten lactating women resulted in a mean C of 2.61 μg/mL (range: 1.57 to 3.65 μg/mL).
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 0.94 to 1.14 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 0.36 to 0.71 over the first 72 hours following dosing.
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 A 3-hour hemodialysis session decreases plasma concentrations by approximately 50%.
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.
Non-Clinical Toxicology
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 and(Seeand Clinically or potentially significant drug interactions between fluconazole and the following agents/classes have been observed. These are described in greater detail below:
Oral hypoglycemicsCoumarin-type anticoagulantsPhenytoinCyclosporineRifampinTheophyllineTerfenadineCisaprideAstemizoleRifabutinTacrolimusShort-term benzodiazepines
Astemizole:
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 .) The data presently available indicate that the decreases in some individual ethinyl estradiol and levonorgestrel AUC values with fluconazole treatment are likely the result of random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol and levonorgestrel, there is no evidence that fluconazole is a net inducer of ethinyl estradiol or levonorgestrel metabolism. The clinical significance of these effects is presently unknown.
Physicians should be aware that interaction studies with medications other than those listed in the section have not been conducted, but such interactions may occur.
Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been rare cases of QT prolongation and torsade de pointes in patients taking fluconazole. Most of these reports involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant medications that may have been contributory.
Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).