Fluconazole
Systematic (IUPAC) name
2-(2,4-difluorophenyl)- 1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol
Identifiers
CAS number	86386-73-4
ATC code	D01AC15 J02AC01
PubChem	3365
DrugBank	APRD00327
Chemical data
Formula	C13H12N6F2O
Mol. weight	306.271 g/mol
Pharmacokinetic data
Bioavailability	>90%
Protein binding	11–12%
Metabolism	Hepatic 11%
Half life	30 hours (range 20-50 hours)
Excretion	Renal 61–88%
Therapeutic considerations
Pregnancy cat.	D (Au), C (U.S.) Image File history File links Fluconazole_structure. ... IUPAC nomenclature is a systematic way of naming organic chemical compounds. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules . ... DrugBank is a database available at the University of Alberta that provides information about thousands of products. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Atomic mass 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless Atomic mass 14. ... General Name, Symbol, Number fluorine, F, 9 Chemical series halogens Group, Period, Block 17, 2, p Appearance Yellowish brown gas Atomic mass 18. ... General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Atomic mass 15. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Many drugs are bound to Blood plasma proteins. ... Metabolism (from Greek μεταβολισμός metabolismos) is the biochemical modification of chemical compounds in living organisms and cells. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... Motto: None Anthem: Advance Australia Fair Royal anthem: God Save the Queen Capital Canberra Largest city Sydney (Population) Brisbane (Size) English (de facto 1) Government Constitutional monarchy (federal)  - Queen Elizabeth II  - Governor-General Michael Jeffery  - Prime Minister John Howard Independence from the UK   - Constitution 1 January 1901   - Statute of Westminster... United States is the current Good Article Collaboration of the week! Please help to improve this article to the highest of standards. ...
Legal status	S3/S4 (Au), POM (UK), ℞-only (U.S.) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Routes	Oral, IV, topical

Fluconazole (INN) (IPA: [fluˈkɒnəzoʊl]) is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. It is commonly marketed under the trade name Diflucan (Pfizer). In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... For information on how to read IPA transcriptions of English words see here. ... Triazole refers to either one of a pair of isomeric chemical compounds with molecular formula C2H3N3, having a five-membered ring of two carbon atoms and three nitrogen atoms. ... An antifungal drug is medication used to treat fungal infections such as athletes foot, ringworm and candidiasis (thrush), as well as serious systemic infections like cryptococcal meningitis. ... Pfizer, Incorporated (NYSE: PFE), is a global pharmaceutical company, with headquarters in New York City. ...

Pharmacology

Mode of action

Like other imidazole- and triazole-class antifungals, fluconazole inhibits the fungal cytochrome P450 enzyme 14α-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cell wall, and subsequent accumulation of 14α-methyl sterols.^[1] Fluconazole is primarily fungistatic, however may be fungicidal against certain organisms in a dose-dependent manner. Imidazole is a heterocyclic aromatic organic compound. ... Triazole refers to either one of a pair of isomeric chemical compounds with molecular formula C2H3N3, having a five-membered ring of two carbon atoms and three nitrogen atoms. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Lanosterol is a tetracyclic triterpenoid which is the compound from which all steroids are derived. ... Ergosterol (ergosta-5,7,22-trien-3β-ol), a sterol, is the biological precursor to Vitamin D2. ... A cell wall is a fairly rigid layer surrounding a cell located outside of the plasma membrane that provides additional support and protection. ... Fungicidal prevents and combats fungal infection. ...

Microbiology

Fluconazole is active against the following microorganisms:^[2]

• Blastomyces dermatitidis
• Candida spp. (except C. krusei and C. glabrata)
• Coccidioides immitis
• Cryptococcus neoformans
• Epidermophyton spp.
• Histoplasma capsulatum
• Microsporum spp.
• Trichophyton spp.

Species Candida albicans Candida dubliniensis Candida glabrata Candida guilliermondii Candida kefyr Candida krusei Candida lusitaniae Candida parapsilosis Candida tropicalis Candida utilis Candida is a genus of yeasts (the most important being Candida albicans) that can cause fungal infections (candidiasis or thrush) in humans and other animals. ... Binomial name Coccidioides immitis Coccidioides immitis is a fungus that resides in the soil in certain parts of the southwestern United States, northern Mexico, and a few other areas in the Western Hemisphere. ... Cryptococcus neoformans is an encapsulated yeastlike fungus that can live in both plants and animals. ... Epidermophyton is a type of fungus causing superficial mycoses. ... Histoplasma capsulatum is a fungus that causes histoplasmosis. ...

Pharmacokinetics

Following oral dosing, fluconazole is almost completely absorbed within two hours. Bioavailability is not significantly affected by concomitant intake of meals or the use of H₂-antagonists (e.g. ranitidine). Concentrations measured in the urine and skin are approximately 10 times the plasma concentration, while saliva, sputum and vaginal fluid concentrations are approximately equal to the plasma concentration, following a standard dose range of between 100mg and 400mg per day. The elimination half-life of fluconazole follows zero order kinetics and only 10% of elimination is due to metabolism, the remainder is excreted in urine and sweat. Patients with impaired renal function will be at risk of overdose as well as patients taking drugs such as Warafin. An H2-receptor antagonist, often shortened to H2 antagonist, is a drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. ... Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ...

Clinical use

Indications

Fluconazole is indicated for the treatment and prophylaxis of fungal infections where other antifungals have failed or are not tolerated (e.g. due to adverse effects), including:^[3] Prophylaxis refers to any medical or public health procedure whose purpose is to prevent, rather than treat or cure, disease. ...

• Candidiasis caused by susceptible strains of Candida
• Tinea corporis, tinea cruris or tinea pedis
• Onychomycosis
• Cryptococcal meningitis

Fluconazole can be used first-line for the following indications:^[3] Ringworms can also refer to fans of the Japanese Ring series of horror novels and films, as well as the US remake. ... Jock itch, also called tinea cruris or ringworm of the groin, is an infection of the groin area caused by fungi. ... Athletes foot is a fungal infection of the skin, usually between the toes, caused by parasitic fungi. ... Onychomycosis means fungal infection of the nails. ... Meningitis is the inflammation of the membranes (meninges) covering the brain, usually due to bacterial or viral infections elsewhere in the body that has spread into the blood and into the cerebrospinal fluid (CSF). ...

• Coccidioidomycosis
• Cryptococcosis
• Histoplasmosis
• Prophylaxis of candidiasis in immunocompromised people

Immunosuppression is the medical suppression of the immune system. ...

Dosage

Dosage varies with indication and between patient groups, ranging from: a two week course of 150mg/day for vulvovaginal candidiasis, to 150–300 mg once weekly for resistant skin infections or some prophylactic indications. 50–600 mg/day may be used for systemic or severe infections, and in urgent infections such as meningitis caused by yeast 800mg/day have been used. Pediatric doses are measured at 8mg/kg max. A loading dose will be indicated when entering a daily dosage schedule, for exaple a loading dose of 200mg on the first day is commonly used with 150mg/day following that.^[3]

Contraindications

Fluconazole is contraindicated in patients with:^[3]

• Known hypersensitivity to fluconazole or other azole antifungals
• Concomitant use of cisapride, due to risk of serious cardiac arrhythmias

Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4 agonist. ... Cardiac arrhythmia is a group of conditions in which the muscle contraction of the heart is irregular or is faster or slower than normal. ...

Precautions

Fluconazole therapy has been associated with QT interval prolongation, which may lead to serious cardiac arrhythmias. Thus it is used with caution in patients with risk factors for prolonged QT interval such as electrolyte imbalance or use of other drugs which may prolong the QT interval (particularly cisapride). In medicine, specifically cardiology, the study of the heart, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the hearts electrical cycle. ... Cardiac arrhythmia is a group of conditions in which the muscle contraction of the heart is irregular or is faster or slower than normal. ... Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4 agonist. ...

Fluconazole has also rarely been associated with severe or lethal hepatotoxicity and liver function tests are usually performed regularly during fluconazole therapy. Additionally, it is used with caution in patients with pre-existing liver disease.^[1] Hepatotoxicity (from hepatic toxicity) is chemical-driven liver damage. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ...

High concentrations of fluconazole have been detected in human breast milk from patients receiving fluconazole therapy, thus its use is not recommended in breastfeeding mothers.^[1] Breast milk usually refers to the milk produced by a human female which is usually fed to infants by breastfeeding. ...

Adverse effects

Adverse drug reactions associated with fluconazole therapy include:^[3] An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ...

• Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhoea, and/or elevated liver enzymes
• Infrequent (0.1–1% of patients): anorexia, fatigue, constipation
• Rare (<0.1% of patients): oliguria, hypokalaemia, dizziness, paraesthesia, seizures, alopecia, Stevens-Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including hepatic failure, anaphylactic/anaphylactoid reactions
• Very rare: prolonged QT interval, torsades de pointes

Anorexia (deriving from the Greek α(ν)- (a(n)-, a prefix that denotes absence) + όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... Renal failure is when the kidneys fail to function properly. ... Hypokalemia is a condition in which the body fails to retain sufficient potassium to maintain health. ... Paresthesia (paraesthesia in British) is a sensation of tingling, pricking, or numbness of the skin with no apparent physical cause, more generally known as the feeling of pins and needles. ... Alopecia is a set of disorders ranging from male and female pattern alopecia (alopecia androgenetica), to alopecia areata, which involves the loss of some of the hair from the head, alopecia totalis, which involves the loss of all head hair, to the most extreme form, alopecia universalis, which involves the... Stevens-Johnson syndrome (SJS) is a severe and potentially life-threatening (15% of cases) disease, it is a hypersensitivity complex affecting the skin and the mucous membranes, a severe expression of erythema multiforme (EM) (and so SJS is also called erythema multiforme major). ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... Dyscrasia (from Greek Dyskrasia, meaning bad mixture), in Ancient Greek medicine, is the imbalance of the four humours, and was believed to be the direct cause of all disease. ... Hepatotoxicity (from hepatic toxicity) is chemical-driven liver damage. ... Liver failure is the final stage of liver disease. ... In medicine, anaphylaxis is a severe and rapid systemic allergic reaction. ... In medicine, specifically cardiology, the study of the heart, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the hearts electrical cycle. ... Torsades de pointes is a medical condition, the name of which means in French twisting of the points. It is a potentially deadly form of ventricular tachycardia. ...

Drug interactions

Fluconazole is an inhibitor of the human cytochrome P450 system, particularly the isozymes CYP2C9 and CYP3A4. In theory, therefore, fluconazole decreases the metabolism and increases the concentration of any drug metabolised by these enzymes. Additionally, its potential effect on QT interval increases the risk of cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval. Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Cytochrome P450 2C9 (abbreviated CYP2C9), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. ... Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1. ... In medicine, specifically cardiology, the study of the heart, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the hearts electrical cycle. ... Cardiac arrhythmia is a group of conditions in which the muscle contraction of the heart is irregular or is faster or slower than normal. ...

References

The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly general practitioners and pharmacists) in Australia. ...