Fluconazole

306.27100

306.27

8VZV102JFY

758661

DTXSID3020627

C500

White crystalline powder|Crystals from ethyl acetate/hexane

J02AC01|D - Dermatologicals|J - Antiinfectives for systemic use

2933990090

81.65000

0.4

Solid

1.49 g/cm3

138-140 °C

579.8ºC at 760 mmHg

304.4ºC

1.663

1g/L(temperature not stated)

-20ºC

3.0X10-9 mm Hg at 25 deg C (est)

1.76None

Henry's Law constant = 1.0X10-13 atm-cu m/mole at 25 °C (est)

1.76|pKa = 2.27 (1,2,4-triazole)

163.9 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|163.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 11.1X10-12 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

3

R36/37/38

S26; S36/37/39; S24/25

XZ4810000

Xn

P261-P305 + P351 + P338

H302-H315-H319-H335

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl fluconazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P263, P264, P270, P271, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P309+P311, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 296 companies from 28 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

**Acute oral toxicity (LD50)**: 1271 mg/kg (rat) [MSDS] **Overdose information** Fluconazole overdoses have been associated with hallucination and paranoia, sometimes in combination. In cases of overdose, employ supportive treatment. Gastric lavage may be necessary. Other modalities such as forced diuresis or hemodialysis may also be used. **A note on liver toxicity** The FDA label warns that this drug carries a risk of hepatotoxicity. Rare but serious cases of serious hepatic toxicity have been reported, especially in patients with serious underlying medical conditions using fluconazole. This group of patients has an increased risk of fatality when using fluconazole. In patients with existing liver dysfunction, use caution during fluconazole therapy. Those who are found to have abnormal liver function tests during therapy should be carefully monitored for the development of increasingly severe injury to the liver. Fluconazole should be stopped if its use is likely to be the underlying cause of liver injury, and medical attention should be sought. Fluconazole induced hepatotoxicity is usually reversible. **Carcinogenesis, mutagenesis, and impairment of fertility** Fluconazole demonstrated no evidence of carcinogenic risk in mice and rats treated orally for 24 months at doses equivalent to approximately 2-7 time the recommended human dose). Male rats given fluconazole at doses equivalent to supratherapeutic human doses showed an increased incidence of hepatocellular adenomas. Cytogenetic studies in vivo and in vitro demonstrated no sign of chromosomal mutation. The significance of these findings for humans is unknown. **Use in pregnancy** There are no sufficient and well-controlled studies of fluconazole use in pregnant women. Available human data do not show an increased risk of congenital anomalies after pregnant women were treated with standard doses (<200 mg/day) of fluconazole, either in a single dose or multiple doses in the first trimester did not appear to impact the fetus negatively. Several case reports describe rare but striking congenital anomalies observed in infants who were exposed to fluconazole at high doses reaching 400-800 mg/day, primarily in the first trimester of pregnancy. Similar findings were observed in animal studies. If this drug is administered during pregnancy, or if the patient becomes pregnant while taking fluconazole, the risk should be discussed thoroughly. **Use in nursing** Fluconazole is secreted in breastmilk at high concentrations. Exercise caution if this drug is used during nursing.

Transient mild-to-moderate elevations in serum aminotransferase levels occur in up to 5% of patients treated with fluconazole, but these abnormalities are usually asymptomatic and resolve even with continuation of the medication. ALT elevations above 8 times the upper limit of normal are reported to occur in 1% of patients taking fluconazole and to represent the most common adverse event leading to early discontinuation of treatment. Clinically apparent hepatotoxicity due to fluconazole is rare, but well described. The liver injury is typically hepatocellular, arises within the first few weeks of therapy and can be accompanied by signs of hypersensitivity such as fever, rash and eosinophilia. Fatal instances of fluconazole induced liver injury have been reported (Case 1), but most cases are self-limited, although recovery may be delayed for several weeks after stopping fluconazole and may be slow requiring 2 to 3 months.

Concurrent use of fluconazole and short-acting benzodiazepines, such as midazolam, may increase the concentration of the benzodiazepine and increase the psychomotor effects; consider decreasing the benzodiazepine dose and monitor the patient carefully for signs of increased benzodiazepine exposure.|Concurrent use of fluconazole and/or itraconazole with tolbutamide, chlorpropamide, glyburide, or glipizide has increased the plasma concentrations of these sulfonylurea agents; hypoglycemia has been noted; blood glucose concentrations should be monitored, and the dose of the oral hypoglycemic agent may need to be reduced.|... In a small study, fluconazole was given with terfenadine and a small pharmacokinetic interaction was found; although no change in cardiac repolarization or accumulation of parent terfenadine was found, concurrent use of terfenadine with fluconazole at doses of 400 mg or greater per day is contraindicated.|Concurrent use of cisapride with fluconazole ... is contraindicated; concurrent use of this antifungal may inhibit the cytochrome P450 enzyme metabolic pathways, resulting in elevated plasma concentrations of cisapride ; this has led to ventricular arrhythmias, including torsades de pointes and QT prolongation ...|For more Interactions (Complete) data for FLUCONAZOLE (17 total), please visit the HSDB record page.

Fluconazole was tested on female B6C3F1 mice. The doses of fluconazole ranged from 1.0% to 10% in 100% ethanol for sensitization and 10% for challenge. Mice received 20 ul by direct dermal application for 5 consecutive days to a prepared site. Site preparation included intradermal injection of Freund's complete adjuvant in some mice. DNFB (1-fluoro-2,4-dinitrobenzene, 99.6%, Sigma Chemical Co.) was used as a positive control at a concentration of 0.25% for sensitization and 0.5% for challenge. Measurement of the contact hypersensitivity response was accomplished by the mouse ear swelling test (MEST). No statistically significant (p < 0.05) or dose-dependent (p < 0.05) contact hypersensitivity response to fluconazole could be detected.

In patients with impaired renal function, plasma concentrations of fluconazole are higher and the half-life prolonged; elimination half-life of the drug is inversely proportional to the patient's creatinine clearance. In addition, there is limited evidence that elimination of the drug may be impaired in geriatric patients.

The protein binding of fluconazole is low and estimated to be 11 to 12%.

Fluconazole's production and use as an antifungal agent(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5.3X10+4(SRC), determined from a structure estimation method(2), indicates that fluconazole is expected to be immobile in soil(SRC). Volatilization of fluconazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.0X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Fluconazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-9 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5.3X10+4(SRC), determined from a structure estimation method(2), indicates that fluconazole is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.0X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from an estimated log Kow of 0.25(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fluconazole, which has an estimated vapor pressure of 3.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fluconazole may be removed from the air by wet and dry deposition(SRC). Fluconazole does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Fluconazole is not expected to undergo hydrolysis in the environment due to lack of functional groups that would hydrolyze under environmental conditions(1). Fluconazole does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.2 was calculated for fluconazole(SRC), using an estimated log Kow of 0.25(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of fluconazole can be estimated to be 5.3X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that fluconazole is expected to be immobile in soil.

The Henry's Law constant for fluconazole is estimated as 1.0X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that fluconazole is expected to be essentially nonvolatile from moist soil(SRC) and water surfaces(2). Fluconazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3X10-9 mm Hg(3) (SRC), determined from a fragment constant method(3).

While data specific to fluconazole were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Another concern is that selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils(1).

EXPERIMENTAL: Fluconazole is distributed into human milk at concentrations similar to those achieved in plasma. Administration of a single 150-mg oral dose to several nursing women resulted in peak plasma fluconazole concentrations of 2.61 ug/mL (range: 1.57-3.65 ug/mL).

Occupational exposure to fluconazole may occur through dermal contact with this compound at workplaces where fluconazole is produced or used. Exposure to fluconazole among the general population may be limited to those administered the drug diflucan, an antifungal. (SRC)

Fluconazole can be administered in the treatment of the following fungal infections: 1) Vaginal yeast infections caused by Candida 2) Systemic Candida infections 3) Both esophageal and oropharyngeal candidiasis 4) Cryptococcal meningitis 5) UTI (urinary tract infection) by Candida 6) Peritonitis (inflammation of the peritoneum) caused by Candida **A note on fungal infection prophylaxis** Patients receiving bone marrow transplantation who are treated with cytotoxic chemotherapy and/or radiation therapy may be predisposed to candida infections, and may receive fluconazole as prophylactic therapy. **A note on laboratory testing** Obtaining specimens for fungal culture and other important laboratory studies such as serology or pathology is advised before starting fluconazole therapy in order to isolate the organisms to be eliminated through treatment. It is permissible to start therapy before the results are available, however, adjusting the therapy once laboratory results confirm the causative organism may be necessary.|FDA Label

Fluconazole is a triazole fungistatic agent used in the treatment of systemic and superficial fungal infections. Fluconazole therapy can cause transient mild-to-moderate serum aminotransferase elevations and is a known cause of clinically apparent acute drug induced liver injury.

Antifungal Agents

Mesh Heading: Antifungal agents|MEDICATION: Antifungal; Orally active bistriazole antifungal agent|MEDICATION (VET): Used to treat systemic mycoses, particularly CNS-related conditions in dogs.|Fluconazole ... /is/ indicated for the prophylaxis of febrile neutropenia in patients with hematologic malignancies. /NOT included in US product labeling/|For more Therapeutic Uses (Complete) data for FLUCONAZOLE (16 total), please visit the HSDB record page.

Although serious adverse hepatic effects have been reported only rarely with fluconazole, the possibility that these effects may occur during fluconazole therapy should be considered. Fluconazole therapy should be discontinued if signs and symptoms consistent with liver disease develop. If abnormal liver function test results occur during fluconazole therapy, the patient should be monitored for the development of more severe hepatic injury.|Serious hepatic reactions (eg, necrosis, clinical hepatitis, cholestasis, fulminant hepatic failure) have been reported rarely in patients receiving fluconazole therapy. The manufacturer states that a clear relationship between these hepatic effects and daily dosage, duration of therapy, gender, or age has not been demonstrated. While hepatotoxicity usually has been reversible, fatalities have been reported. Fatalities principally have occurred in patients with serious underlying disease (eg, AIDS, malignancy) who were receiving fluconazole concomitantly with other drugs; however, at least one fatality involved an immunocompetent geriatric individual with renal impairment who developed fulminant hepatic necrosis within 10 days after fluconazole therapy was initiated.|Mild, transient increases (1.5-3 times the upper limit of normal) in serum concentrations of AST (SGOT), ALT (SGPT), alkaline phosphatase, gamma-glutamyltransferase (GGT, gamma-glutamyl transpeptidase, GGTP), and bilirubin have been reported in about 5-7% of patients receiving fluconazole. In most reported cases, concentrations returned to pretreatment levels either during or after fluconazole therapy and were not associated with hepatotoxicity. However, higher increases in serum transaminase concentrations (8 or more times the upper limit of normal), which required discontinuance of the drug, have been reported in about 1% of patients receiving fluconazole. Any patient who develops abnormal liver function test results while receiving fluconazole should be closely monitored for the development of more severe hepatic injury.|Because potentially fatal exfoliative skin disorders have been reported rarely in patients with a serious underlying disease receiving fluconazole, the possibility that these effects can occur should be considered. Immunocompromised patients (e.g., patients with HIV infections) who develop rash during fluconazole therapy should be monitored closely and the drug discontinued if the lesions progress.|For more Drug Warnings (Complete) data for FLUCONAZOLE (17 total), please visit the HSDB record page.

Fluconazole has been demonstrated to show fungistatic activity against the majority of strains of the following microorganisms, curing fungal infections: _Candida albicans, Candida glabrata (Many strains are intermediately susceptible), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans_ This is achieved through steroidal inhibition in fungal cells, interfering with cell wall synthesis and growth as well as cell adhesion, thereby treating fungal infections and their symptoms. The fungistatic activity of fluconazole has also been shown in normal and immunocompromised animal models with both systemic and intracranial fungal infections caused by _Cryptococcus neoformans_ and for systemic infections caused by Candida albicans. It is important to note that resistant organisms have been found against various strains of organisms treated with fluconazole. This further substantiates the need to perform susceptibility testing when fluconazole is considered as an antifungal therapy. **A note on steroidal effects of fluconazole** There has been some concern that fluconazole may interfere with and inactivate human steroids/hormones due to the inhibition of hepatic cytochrome enzymes. Fluconazole has demonstrated to be more selective for _fungal_ cytochrome P-450 enzymes than for a variety of mammalian cytochrome P-450 enzymes. Fluconazole 50 mg administered daily for up to 28 days in individuals of reproductive age has been show to have no effect on testosterone plasma concentrations of males and plasma concentrations of steroids in females. A 200-400 mg dose of fluconazole showed no clinically relevant effect on steroid levels or on ACTH-stimulated steroid response in healthy males, in one clinical study mentioned on the European Medicines Agency label. Other studies have shown no significant effects of fluconazole on steroid levels, further confirming these data.

Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism. (See all compounds classified as 14-alpha Demethylase Inhibitors.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C19. (See all compounds classified as Cytochrome P-450 CYP2C19 Inhibitors.)|Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C9. (See all compounds classified as Cytochrome P-450 CYP2C9 Inhibitors.)

The pharmacokinetic properties of fluconazole are comparable after administration by the intravenous (IV) and oral (PO) routes. In healthy volunteers, the bioavailability of orally administered fluconazole is measured to be above 90%. It is extensively absorbed in the gastrointestinal tract when an oral dose is taken. Oral absorption is not affected by food intake with fluconazole but may increase the time until the maximum concentration is reached. Tmax (or the time taken to achieve the maximum concentration) in one clinical study of healthy patients receiving 50 mg/kg of fluconazole was 3 hours. Peak plasma concentrations (Cmax) in fasting and healthy volunteers occur between 1-2 hours post-dose. Steady-state concentrations are achieved within 5 to 10 days after oral doses of 50-400 mg administered once daily. Administration of a loading dose on the first day of fluconazole treatment, or twice the usual daily dose, leads to plasma concentrations close to steady-state by the second day. Mean AUC (area under the curve) was 20.3 in healthy volunteers receiving 25 mg of fluconazole. **A note on the capsule and powder form and malabsorption syndromes** The capsule forms of fluconazole often contain lactose and should not be administered with hereditary galactose intolerance, _Lapp lactase enzyme_ deficiency, or malabsorption of glucose/galactose. The powder form, used for the oral suspension, lists sucrose as an ingredient and should not be used in patients who have been diagnosed with fructose, glucose/galactose malabsorption, and _sucrase-isomaltase_ enzyme deficiency.|In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose measured in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites.. A study of a 50mg radiolabeled dose of fluconazole revealed that 93.3% of the dose was found excreted in the urine. **A note on renal failure** The pharmacokinetics of fluconazole are significantly affected by renal dysfunction. The dose of fluconazole may need to be reduced in patients with decreased renal function. A 3-hour hemodialysis treatment lowers plasma fluconazole concentrations by about 50%.|The apparent volume of distribution is said to be similar to the volume of distribution of total body water. One clinical study of healthy volunteers administered 50 mg/kg of fluconazole was 39L, based on a body weight of 60kg. Fluconazole shows substantial penetration in many body fluids, which is a property that renders it an ideal treatment for systemic fungal infections, especially when administered over a longer time. Fluconazole is found in high concentrations in the stratum corneum and dermis-epidermis of skin, in addition to eccrine sweat. Fluconazole is found to accumulate especially well in the stratum corneum, which is beneficial in superficial fungal infections. Saliva and sputum concentrations of fluconazole are found to be similar to the plasma concentrations. In patients diagnosed with fungal meningitis, fluconazole CSF (cerebrospinal fluid) levels are measured to be about 80% of the corresponding plasma levels. Therefore, fluconazole crosses the blood-brain barrier. The meninges are increasingly permeable to fluconazole in states of inflammation, facilitating treatment in meningitis.|This drug is mainly eliminated by the kidneys and the mean body clearance in adults is reported to be 0.23 mL/min/kg. One clinical study of healthy subjects showed total clearance of 19.5 ± 4.7 mL/min and renal clearance of 14.7 ± 3.7 mL/min (1.17 ± 0.28 and 0.88 ± 0.22 L/h). Clearance in the pediatric population varies according to age, as does clearance in patients with renal failure.|The pharmacokinetics of fluconazole are similar following IV or oral administration. The drug is rapidly and almost completely absorbed from the GI tract, and there is no evidence of first-pass metabolism. Oral bioavailability of fluconazole exceeds 90% in healthy, fasting adults; peak plasma concentrations of the drug generally are attained within 1-2 hours after oral administration. ... The rate and extent of GI absorption of fluconazole are not affected by food. The manufacturer states that the commercially available fluconazole suspensions are bioequivalent to the 100-mg fluconazole tablets.|Peak plasma fluconazole concentrations and AUCs increase in proportion to the dose over the oral dosage range of 50-400 mg. Steady-state plasma concentrations of fluconazole are attained within 5-10 days following oral doses of 50-400 mg given once daily. ... When fluconazole therapy is initiated with a single loading dose equal to twice the usual daily dosage and followed by the usual dosage given once daily thereafter, plasma concentrations of the drug reportedly approach steady state by the second day of therapy.|In healthy, fasting adults who received a single 1-mg/kg oral dose of fluconazole, peak plasma concentrations of the drug averaged 1.4 mcg/mL. Following oral administration of a single 400-mg dose of fluconazole in healthy, fasting adults, peak plasma concentrations average 6.72 mcg/mL (range: 4.12-8.1 mcg/mL).|In healthy adults receiving 50- or 100-mg doses of fluconazole given once daily by IV infusion over 30 minutes, serum concentrations of the drug 1 hour after dosing on the sixth or seventh day of therapy ranged from 2.14-2.81 or 3.86-4.96 mcg/mL, respectively.|For more Absorption, Distribution and Excretion (Complete) data for FLUCONAZOLE (14 total), please visit the HSDB record page.

Fluconazole is metabolized minimally in the liver. Fluconazole is an inhibitor of CYP2C9, CYP3A4 and CYP2C19. Two metabolites were detected in the urine of healthy volunteers taking a 50 mg radiolabeled dose of fluconazole; a glucuronidated metabolite on the hydroxyl moiety (6.5%) and a fluconazole N-oxide metabolite (2%). The same study indicated that no signs of metabolic cleavage of fluconazole were observed, suggesting a difference in metabolism when compared to other agents in the same drug class, which are heavily metabolized in the liver.|Hepatic accounts for <10% of elimination

The terminal elimination half-life in the plasma is approximately 30 hours (range: 20-50 hours) after oral administration. The long plasma elimination half-life supports a single dose therapy for vaginal candidiasis, once daily and once weekly dosing for other indications.. Patients with renal failure may require dosage adjustment, and half-life can be significantly increased in these patients.|The plasma elimination half-life of fluconazole in adults with normal renal function is approximately 30 hours (range: 20-50 hours). In one study, plasma elimination half-life of the drug was 22 hours after the first day of therapy and 23.8 and 28.6 hours after 7 and 26 days of therapy, respectively.|In a limited, single-dose study in HIV-infected adults, the plasma elimination half-life of fluconazole averaged 32 hours (range: 25-42 hours) in those with absolute helper/inducer (CD4+, T4+) T-cell counts greater than 200 cu m and 50 hours (range: 32-69 hours) in those with CD4+ T-cell counts less than 200 cu m. In other single-dose studies in a limited number of HIV-infected adults with CD4+ T-cell counts less than 200 cu m, the plasma elimination half-life of the drug averaged 35-40 hours (range 22-75 hours).|The mean plasma half-life of fluconazole in children 9 months to 15 years of age has ranged from about 15-25 hours. In a limited study in premature neonates who received IV fluconazole once every 72 hours, the plasma half-life decreased over time, averaging 88 hours after the first dose and 55 hours after the fifth dose (day 13).

Fluconazole is a very selective inhibitor of fungal cytochrome P450 dependent enzyme _lanosterol 14-α-demethylase_. This enzyme normally works to convert _lanosterol_ to _ergosterol_, which is necessary for fungal cell wall synthesis. The free nitrogen atom located on the azole ring of fluconazole binds with a single iron atom located in the heme group of lanosterol 14-α-demethylase. This prevents oxygen activation and, as a result, inhibits the demethylation of lanosterol, halting the process of ergosterol biosynthesis. Methylated sterols are then found to accumulate in the fungal cellular membrane, leading to an arrest of fungal growth. These accumulated sterols negatively affect the structure and function of the fungal cell plasma membrane. Fluconazole resistance may arise from an alteration in the amount or function of the target enzyme (lanosterol 14-α-demethylase), altered access to this enzyme, or a combination of the above. Other mechanisms may also be implicated, and studies are ongoing.|Fluconazole usually is fungistatic in action. Fluconazole and other triazole-derivative antifungal agents (e.g., itraconazole, terconazole) appear to have a mechanism of action similar to that of the imidazole-derivative antifungal agents (e.g., butoconazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole). Like imidazoles, fluconazole presumably exerts its antifungal activity by altering cellular membranes resulting in increased membrane permeability, leakage of essential elements (eg, amino acids, potassium), and impaired uptake of precursor molecules (eg, purine and pyrimidine precursors to DNA). Although the exact mechanism of action of fluconazole and other triazoles has not been fully determined, the drugs inhibit cytochrome P-450 14-a-desmethylase in susceptible fungi, which leads to accumulation of C-14 methylated sterols (e.g., lanosterol) and decreased concentrations of ergosterol. It appears that this may occur because a nitrogen atom (N-4) in the triazole molecule binds to the heme iron of cytochrome P-450 14-a-desmethylase in susceptible fungi. Unlike some imidazoles (eg, clotrimazole, econazole, miconazole, oxiconazole) that suppress ATP concentrations in intact cells and spheroplasts of C. albicans, fluconazole does not appear to have an appreciable effect on ATP concentrations in the organism. It is unclear whether this effect is related to the in vivo antifungal effects of the drugs. Fluconazole generally is fungistatic against Candida albicans when the organism is in either the stationary or early logarithmic phase of growth.|Fungistatic; may be fungicidal, depending on the concentration; azole antifungals interfere with cytochrome P450 enzyme activity, which is necessary for the demethylation of 14-alpha-methylsterols to ergosterol. Ergosterol, the principal sterol in the fungal cell membrane, becomes depleted. This damages the cell membrane, producing alterations in membrane functions and permeability. In Candida albicans, azole antifungals inhibit transformation of blastospores into invasive mycelial form.

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Signs and symptoms of overdose may include hallucinations, paranoid behaviors, decreased motility and respiration, ptosis, urinary incontinence, and cyanosis.|/CASE REPORTS/ While results of several studies evaluating pregnancy outcomes did not indicate an increased risk for congenital malformations in infants born to women who received fluconazole during pregnancy, data from these studies indicate that there has been at least one case each of congenital dislocation of the hip, lacrimal stenosis, partial syndactyly, ventricular septum deficiency, polydactyly or syndactyly, heart defect, or spina bifida in infants born to women who received the drug during pregnancy. In addition, there have been at least 3 reports of congenital abnormalities (craniofacial, skeletal, cardiac) in infants born to women who received fluconazole (400-800 mg daily) for the treatment of coccidioidomycosis during the first trimester.|/CASE REPORTS/ Hallucinations and paranoid behavior developed in a patient with human immunodeficiency virus (HIV) infection who reportedly ingested 8.2 g of fluconazole. The patient was hospitalized, and these manifestations resolved within 48 hours.

Apo Fluconazole

Trade names: Biozolene (Bioindustria), Diflucan (Mason, Pfizer, Roerig), Dimycon (Alkaloid), Elazor (Sigma-Tau), Flavizol (Gador), Fungata (Mack), Mutum (Raffo), Triflucan (Pfizer).|Fluconazole (DIFLUCAN) is marketed in the United States as tablets ... for oral administration, powder for oral suspension ... and iv solutions ... in saline and in dextrose solutions.|Oral: For suspension: 50 mg/5 mL Diflucan, (Pfizer), 200 mg/5 mL Diflucan, (Pfizer); Tablets: 50 mg* Diflucan (with povidone), (Pfizer), 100 mg Diflucan (with povidone), (Pfizer), 150 mg Diflucan (with povidone), (Pfizer), 200 mg Diflucan (with povidone), (Pfizer).

Analyte: fluconazole; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: fluconazole; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: fluconazole; matrix: chemical purity; procedure: dissolution in glacial acetic acid; titration with perchloric acid using an anhydrous electrode system|Analyte: fluconazole; matrix: animal feed; procedure: high-performance liquid chromatography with ultraviolet detection at 210 nm|For more Analytic Laboratory Methods (Complete) data for FLUCONAZOLE (7 total), please visit the HSDB record page.

Analyte: fluconazole; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 260 nm; limit of detection: 1 ng/mL|Analyte: fluconazole; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 210 nm|Analyte: fluconazole; matrix: blood (serum, plasma); urine; cerebral spinal fluid; procedure: high-performance liquid chromatography with ultraviolet detection at 260 nm; limit of detection: 200 ng/mL|Analyte: fluconazole; matrix: blood (plasma); saliva; procedure: high-performance liquid chromatography with ultraviolet detection at 261 nm; limit of quantitation: 100 ng/mL (plasma); 1000 ng/mL (saliva)

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Fungicides