More information about Fluconazole
Pronunciation(floo KOE na zole)
U.S. Brand NamesDiflucan®
Canadian Brand NamesApo-Fluconazole®; Diflucan®; Gen-Fluconazole; Novo-Fluconazole
UseTreatment of candidiasis (vaginal, oropharyngeal, esophageal, urinary tract infections, peritonitis, pneumonia, and systemic infections); cryptococcal meningitis; antifungal prophylaxis in allogeneic bone marrow transplant recipients
Use - DentalTreatment of susceptible fungal infections in the oral cavity including candidiasis, oral thrush, and chronic mucocutaneous candidiasis treatment of esophageal and oropharyngeal candidiasis caused by Candida species; treatment of severe, chronic mucocutaneous candidiasis caused by Candida species
Pregnancy Risk FactorC
Pregnancy ImplicationsWhen used in high doses, fluconazole is teratogenic in animal studies. Following exposure during the first trimester, case reports have noted similar malformations in humans when used in higher doses (400 mg/day) over extended periods of time. Use of lower doses (150 mg as a single dose or 200 mg/day) may have less risk; however, additional data is needed. Use during pregnancy only if the potential benefit to the mother outweighs any potential risk to the fetus.
LactationEnters breast/not recommended (AAP rates "compatible")
ContraindicationsHypersensitivity to fluconazole, other azoles, or any component of the formulation; concomitant administration with cisapride
Warnings/PrecautionsShould be used with caution in patients with renal and hepatic dysfunction or previous hepatotoxicity from other azole derivatives. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored closely and discontinued if symptoms consistent with liver disease develop. Use caution in patients at risk of proarrhythmias.
Adverse ReactionsFrequency not always defined.
Cardiovascular: Angioedema, pallor, QT prolongation, torsade de pointes
Central nervous system: Headache (2% to 13%), seizure, dizziness
Dermatologic: Rash (2%), alopecia, toxic epidermal necrolysis, Stevens-Johnson syndrome
Endocrine & metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia
Gastrointestinal: Nausea (4% to 7%), vomiting (2%), abdominal pain (2% to 6%), diarrhea (2% to 3%), taste perversion, dyspepsia
Hematologic: Agranulocytosis, leukopenia, neutropenia, thrombocytopenia
Hepatic: Hepatic failure (rare), hepatitis, cholestasis, jaundice, increased ALT/AST, increased alkaline phosphatase
Miscellaneous: Anaphylactic reactions (rare)
Overdosage/ToxicologySymptoms of overdose include decreased lacrimation, salivation, respiration and motility, urinary incontinence, and cyanosis. Treatment includes supportive measures. A 3-hour hemodialysis will remove 50%.
Drug InteractionsInhibits CYP1A2 (weak), 2C8/9 (strong), 2C19 (strong), 3A4 (moderate)
Benzodiazepines (metabolized by oxidation, eg, alprazolam, triazolam, midazolam, diazepam) serum concentrations are increased by fluconazole which may cause increased CNS sedation. Consider a benzodiazepine not metabolized by CYP3A4 or another antifungal.
Caffeine's metabolism is decreased; monitor for tachycardia, nervousness, and anxiety.
Calcium channel blockers may have increased serum concentrations; consider another agent instead of a calcium channel blocker, another antifungal, or reduce the dose of the calcium channel blocker. Monitor blood pressure.
Cisapride's serum concentration is increased which may lead to malignant arrhythmias; concurrent use is contraindicated.
Cyclosporine's serum concentration is increased; monitor cyclosporine's serum concentration and renal function.
CYP2C8/9 substrates: Fluconazole may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.
CYP2C19 substrates: Fluconazole may increase the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, and sertraline.
CYP3A4 substrates: Fluconazole may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, cyclosporine, mirtazapine, nateglinide, nefazodone, sildenafil (and other PDE-5 inhibitors), tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.
HMG-CoA reductase inhibitors (except pravastatin and fluvastatin) have increased serum concentrations; switch to pravastatin/fluvastatin or monitor for development of myopathy.
Losartan's active metabolite is reduced in concentration; consider another antihypertensive agent unaffected by the azole antifungals, another antifungal, or monitor blood pressure closely.
Phenytoin's serum concentration is increased; monitor phenytoin levels and adjust dose as needed.
Rifampin decreases fluconazole's serum concentration; monitor infection status.
Tacrolimus's serum concentration is increased; monitor tacrolimus's serum concentration and renal function.
Warfarin's effects are increased; monitor INR and adjust warfarin's dose as needed.
Powder for oral suspension: Store dry powder at
Injection: Store injection in glass at 5°C to 30°C (41°F to 86°F). Store injection in Viaflex® at 5°C to 25°C (41°F to 77°F). Protect from freezing. Do not unwrap unit until ready for use.
CompatibilityStable in D5W, LR, NS
Y-site administration: Compatible: Acyclovir, aldesleukin, allopurinol, amifostine, amikacin, aminophylline, ampicillin/sulbactam, aztreonam, benztropine, cefazolin, cefepime, cefotetan, cefoxitin, cefpirome, chlorpromazine, cimetidine, cisatracurium, dexamethasone sodium phosphate, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin liposome, droperidol, etoposide phosphate, famotidine, filgrastim, fludarabine, foscarnet, ganciclovir, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin, hydrocortisone sodium phosphate, immune globulin intravenous, leucovorin, linezolid, lorazepam, melphalan, meperidine, meropenem, metoclopramide, metronidazole, midazolam, morphine, nafcillin, nitroglycerin, ondansetron, oxacillin, paclitaxel, pancuronium, penicillin G potassium, phenytoin, piperacillin/tazobactam, prochlorperazine edisylate, promethazine, propofol, ranitidine, remifentanil, sargramostim, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tobramycin, vancomycin, vecuronium, vinorelbine, zidovudine. Incompatible: Amphotericin B, amphotericin B cholesteryl sulfate complex, ampicillin, calcium gluconate, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, clindamycin, co-trimoxazole, diazepam, digoxin, erythromycin lactobionate, furosemide, haloperidol, hydroxyzine, imipenem/cilastatin, pentamidine, piperacillin, ticarcillin
Compatibility when admixed: Compatible: Acyclovir, amikacin, amphotericin B, cefazolin, ceftazidime, clindamycin, gentamicin, heparin, meropenem, metronidazole, morphine, piperacillin, potassium chloride, ranitidine with ondansetron, theophylline. Incompatible: Co-trimoxazole
Mechanism of ActionInterferes with cytochrome P450 activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation
Distribution: Widely throughout body with good penetration into CSF, eye, peritoneal fluid, sputum, skin, and urine
Relative diffusion blood into CSF: Adequate with or without inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 70% to 80%; Inflamed meninges: >70% to 80%
Protein binding, plasma: 11% to 12%
Bioavailability: Oral: >90%
Half-life elimination: Normal renal function: ~30 hours
Time to peak, serum: Oral: 1-2 hours
Excretion: Urine (80% as unchanged drug)
DosageThe daily dose of fluconazole is the same for oral and I.V. administration
Neonates: First 2 weeks of life, especially premature neonates: Same dose as older children every 72 hours
Children: Once-daily dosing by indication: See table.
Fluconazole Once-Daily Dosing Children
Adults: Oral, I.V.: Note: Susceptibility for Candida is divided into susceptible, susceptible-dose dependent (SDD), and resistant. Increased dose (up to 400 mg/day) may be used to treat SDD strains, especially when there has been treatment failure at lower doses.
Once-daily dosing by indication: See table.
Dosing adjustment/interval in renal impairment:
Fluconazole Once-Daily Dosing Adults
Dosing adjustment/interval in renal impairment:
No adjustment for vaginal candidiasis single-dose therapy
For multiple dosing, administer usual load then adjust daily doses
Hemodialysis: 50% is removed by hemodialysis; administer 100% of daily dose (according to indication) after each dialysis treatment.
Continuous arteriovenous or venovenous hemofiltration: Dose as for Clcr 10-50 mL/minute.
AdministrationParenteral fluconazole must be administered by I.V. infusion over approximately 1-2 hours; do not exceed 200 mg/hour when giving I.V. infusion
Monitoring ParametersPeriodic liver function tests (AST, ALT, alkaline phosphatase) and renal function tests, potassium
Dietary ConsiderationsTake with or without regard to food.
Patient EducationInform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed, around-the-clock. Take full course of medication as ordered. Take with or without food. Follow good hygiene measures to prevent reinfection. Frequent blood tests may be required. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause headache, dizziness, drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known); or nausea, vomiting, or diarrhea (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report skin rash, redness, or irritation; persistent GI upset; urinary pattern changes; excessively dry eyes or mouth; or changes in color of stool or urine. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Anesthesia and Critical Care Concerns/Other ConsiderationsDo not use if cloudy or precipitated. If administered by I.V. infusion, give over 1-2 hours.
Cardiovascular ConsiderationsFluconazole is contraindicated in patients taking cisapride due to increased risk for significant cardiotoxicity, particularly proarrhythmia.
Dental Health: Effects on Dental TreatmentKey adverse event(s) related to dental treatment: Abnormal taste.
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Mental Health: Effects on Mental StatusMay cause dizziness and seizures
Mental Health: Effects on Psychiatric TreatmentNone reported; CYP3A4 inhibitor; use caution with triazolam, alprazolam, and midazolam
Oncology: Emetic PotentialVery low (<10%)
Infusion [premixed in sodium chloride]: 2 mg/mL (100 mL, 200 mL)
Diflucan® [premixed in sodium chloride or dextrose] 2 mg/mL (100 mL, 200 mL)
Powder for oral suspension (Diflucan®): 10 mg/mL (35 mL); 40 mg/mL (35 mL) [contains sodium benzoate; orange flavor]
Tablet (Diflucan®): 50 mg, 100 mg, 150 mg, 200 mg
Aleck KA and Bartley DL, "Multiple Malformation Syndrome Following Fluconazole Use in Pregnancy: Report of an Additional Patient,"Am J Med Genet, 1997, 72(3):253-6.
"American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,"Pediatrics, 2001, 108(3):776-89.
Amichai B and Grunwald MH, "Adverse Drug Reactions of the New Oral Antifungal Agents - Terbinafine, Fluconazole, and Itraconazole,"Int J Dermatol, 1998, 37(6):410-5.
Berl T, Wilner KD, Gardner M, et al, "Pharmacokinetics of Fluconazole in Renal Failure,"J Am Soc Nephrol, 1995, 6(2):242-7.
Como JA and Dismukes WE, "Oral Azole Drugs as Systemic Antifungal Therapy,"N Engl J Med, 1993, 330(4):263-72.
Edwards JE Jr, Bodey GP, Bowden RA, et al, "International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections,"Clin Infect Dis, 1997, 25(1):43-59.
Eggimann P, Francioli P, Bille J, et al, "Fluconazole Prophylaxis Prevents Intra-Abdominal Candidiasis in High-Risk Surgical Patients,"Crit Care Med, 1999, 27(6):1066-72.
Force RW, "Fluconazole Concentrations in Breast Milk,"Pediatr Infect Dis J, 1995, 14(3):235-6.
Goa KL and Barradell LB, "Fluconazole. An Update of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use in Major Superficial and Systemic Mycoses in Immunocompromised Patients,"Drugs, 1995, 50(4):658-90.
Goodman JL, Winston DJ, Greenfield RA, et al, "A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation,"N Engl J Med, 1992, 326(13):845-51.
Grant SM and Clissold SP, "Fluconazole: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Potential in Superficial and Systemic Mycoses,"Drugs, 1990, 39(6):877-916.
Kauffman CA and Carver PL, "Antifungal Agents in the 1990s. Current Status and Future Developments,"Drugs, 1997, 53(4):539-49.
Kowalsky SF and Dixon DM, "Fluconazole: A New Antifungal Agent,"Clin Pharm, 1991, 10(3):179-94.
Lee JW, Seibel NL, Amantea M, et al, "Safety and Pharmacokinetics of Fluconazole in Children With Neoplastic Diseases,"J Pediatr, 1992, 120(6):987-93.
Lyman CA and Walsh TJ, "Systemically Administered Antifungal Agents. A Review of Their Clinical Pharmacology and Therapeutic Applications,"Drugs, 1992, 44(1):9-35.
Mastroiacovo P, Mazzone T, Botto LD, et al, "Prospective Assessment of Pregnancy Outcomes After First-Trimester Exposure to Fluconazole,"Am J Obstet Gynecol, 1996, 175(6):1645-50.
Mercurio MG and Elewski BE, "Thrombocytopenia Caused by Fluconazole Therapy,"J Am Acad Dermatol, 1995, 32(3):525-6.
Moncino MD and Gutman LT, "Severe Systemic Cryptococcal Disease in a Child: Review of Prognostic Indicators Predicting Treatment Failure and an Approach to Maintenance Therapy With Oral Fluconazole,"Pediatr Infect Dis J, 1990, 9(5):363-8.
Pappas PG, Rex JH, Sobel JD, et al, "Guidelines for Treatment of Candidiasis. Infectious Diseases Society of America,"Clin Infect Dis, 2004, 38(2):161-89.
Pelz RK, Hendrix CW, Swoboda SM, et al, "Double-Blind Placebo-Controlled Trial of Fluconazole to Prevent Candidal Infections in Critically Ill Surgical Patients,"Ann Surg, 2001, 233(4):542-8.
Perry CM, Whittington R, and McTavish D, "Fluconazole. An Update of Its Antimicrobial Activity, Pharmacokinetic Properties, and Therapeutic Use in Vaginal Candidiasis,"Drugs, 1995, 49(6):984-1006.
Rex JH, Bennett JE, Sugar AM, "A Randomized Trial Comparing Fluconazole With Amphotericin B for the Treatment of Candidemia in Patients Without Neutropenia. Candidemia Study Group and the National Institute,"N Engl J Med, 1994, 331(20):1325-30.
Rex JH, Walsh TJ, Sobel JD, et al, "Practice Guidelines for the Treatment of Candidiasis, Infectious Diseases Society of America,"Clin Infect Dis, 2000, 30(4):662-78.
Saag MS, Graybill RJ, Larsen RA, et al, "Practice Guidelines for the Management of Cryptococcal Disease. Infectious Diseases Society of America,"Clin Infect Dis, 2000, 30(4):710-8.
Sanchez JM and Moya G, "Fluconazole Teratogenicity,"Prenat Diagn, 1998, 18(8):862-3.
Sorensen HT, Nielsen GL, Olesen C, et al, "Risk of Malformations and Other Outcomes in Children Exposed to Fluconazole in utero,"Br J Clin Pharmacol, 1999, 48(2):234-8.
Terrell CL, "Antifungal Agents. Part II. The Azoles,"Mayo Clin Proc, 1999, 74(1):78-100.
Trepanier EF and Amsden GW, "Current Issues in Onchomycosis,"Ann Pharmacother, 1998, 32(2):204-14.
Valtonen M, Tiula E, and Neuvonen PJ, "Effect of Continuous Veno-Venous Haemofiltration and Haemodiafiltration on the Elimination of Fluconazole in Patients With Acute Renal Failure,"J Antimicrob Chemother, 1997, 40(5):695-700.
Viscoli C, Castagnola E, Fioredda F, et al, "Fluconazole in the Treatment of Candidiasis in Immunocompromised Children,"Antimicrob Agents Chemother, 1991, 35(2):365-7.
International Brand NamesAfungil® (MX); Apo-Fluconazole® (CA); Azoflune® (PT); Baten® (CO, DO, GT, HN, PA, SV); Béagyne® (FR); Besic Derm® (GT); Biozole® (TH); Canazole® (BD); Cancid® (ID); Candidin® (TR); Candimicol® (AR); Canex® (DE); Ciplaflucon® (CO); Conasol® (DK); Cryptal® (ID); Damicol® (AR); Dexmazol® (EC); Diflazon® (CZ, RO, RU, SI); Diflucan® (AT, AU, BE, CA, CH, CL, CO, CY, CZ, DE, DK, DO, EG, ES, FI, GB, HK, HR, HU, ID, IE, IL, IT, JO, JP, KW, LB, LU, MX, NL, NO, NZ, PL, PT, RO, RU, SE, SG, SI, TH, YU, ZA); Diflucan One® (GB); Elazor® (IT); Flucand® (EG, JO, KW, LB, SY); Flucandid® (IE); Flucan® (TR); Flucazol® (BR, CH); Fluc Hexal® (DE); Flucobeta® (DE); Flucoder® (BD); FlucoLich® (DE); Flucomicon® (DO, EC, GT, HN, PA); Fluconacx® (EC); Fluconal® (BD, BR); Fluconazol 1A Farma® (DK); Fluconazol 1A-Pharma® (DE); Fluconazol AbZ® (DE); Fluconazol AL® (DE); Fluconazol Alpharma® (DK); Fluconazol Alternova® (DK); Fluconazol Bexal® (ES); Fluconazol® (BR, CR, DE, EC, PL); Fluconazol Calox® (CR, PA); Fluconazol Chemo Farma® (ES); Fluconazol Chemo Technic® (ES); Fluconazol Copyfarm® (DK); FLuconazol Crotalchem® (ES); Fluconazol Cuve® (ES); Fluconazol Denver® (AR); Fluconazol Derm 1A Pharma® (DE); Fluconazol DF® (AR); Fluconazol Duncan® (AR); Fluconazole® (PL); Fluconazol Fabra® (AR); Fluconazol Fada® (AR); Fluconazol Gea® (DK); Fluconazol Gemepe® (AR); Fluconazol Genfar® (EC); Fluconazol-GRY® (DE); Fluconazol Hexal® (DE); Fluconazol-Isis® (DE); Fluconazol Martian® (AR); Fluconazol Merck® (ES); Fluconazol MK® (CO, CR, GT, HN, SV); Fluconazol Nycomed® (DK); Fluconazol Paranova® (DK); Fluconazol ratiopharm® (AT); Fluconazol-ratiopharm® (DE); Fluconazol ratiopharm® (DK); Fluconazol Richet® (AR); Fluconazol Rivero® (AR); Fluconazol Roux-Ocefa® (AR); Fluconazol-Slovakofarma® (CZ); Fluconazol Stada® (DE, DK); Fluconazol Vannier® (AR); Fluconazol von ct® (DE); Flucon® (BD); Fluconovag® (AR); Flucoral® (ID); Flucoric® (ZA); Flucosept® (AT); Flucostat® (RU); Flucovim® (RO); Flucoxan® (CL); Flucozol® (DO); Flucozole® (TH); Flucozol Rowe® (EC); Fluctin® (CL); Fludizol® (TH); Fludocel® (PT); Flugal® (BD); Flukonazol NM Pharma® (SE); Flumarin® (DO); Flumicot® (AR); Flumycon® (PL); Flumycozal® (YU); Flunazol® (BR, EC); Flunazul® (DE); Flunco® (TH); Flunizol® (CH); Flurit-D® (TR); Flurit-G® (TR); Flusan® (BR); Fluzol® (AR, ZA); Fluzole® (TR); Forcan® (IN); Fujisen® (CO); Funa® (TH); Funex® (CO); Fungal® (DK); Fungata® (AT, DE); Fungocina® (AR); Fungolon® (BG); Fungustatin Orifarm® (DK); Funizol® (CR, GT, PA, SV); Fuzol Pauly® (CO); Gen-Fluconazole (CA); Govazol® (ID); Honguil Plus® (AR); Ibarin® (CL); Kambine® (EC); Kandizol® (TR); Kyrin® (TH); Lavisa® (ES); Lertus® (BR); Logican® (IN); Loitin® (ES); Lumen® (TR); Medoflucon® (RU); Micofin® (CL); Micofull® (DO); Micolis novo® (AR); Monipax® (BR); Mutum® (AR); Mycocyst® (HU); Mycomax® (CZ, PL, RO); Mycorest® (SG); Mycosyst® (CZ, HU, PL, RU); Neofomiral® (MX); Nifurtox® (AR); Nobzol® (CO); Nor-Fluozol® (SV); Novo-Fluconazole (CA); Omastin® (BD); Oxifungol® (MX); Periplum® (AR); Plusatac® (AR); Plusgin® (CL); Reforce® (PT); Solacap® (ES); Stalene® (TH); Supremase® (PT); Syscan® (IN, RO); Tavor® (CL, CO); Trican® (IL); Triflucan® (AR, FR, IL, TR); Trizol® (TR); Unizol® (BR); Zelix® (BR); Zemyc® (ID); Zolanix® (BR); Zolax® (TR); Zolstatin® (BR); Zoltec® (BR); Zonal® (MX)