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Pronunciation
(floo KOE na zole)
Generic Available (U.S.)
Yes
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of candidiasis (vaginal, oropharyngeal, esophageal, urinary tract infections, peritonitis, pneumonia, and systemic infections); cryptococcal meningitis; antifungal prophylaxis in allogeneic bone marrow transplant recipients
Use: Dental
Treatment 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
Use: Unlabeled/Investigational
Cryptococcal pneumonia; candidal intertrigo
Pregnancy Risk Factor
C
Pregnancy Considerations
When 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.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Fluconazole is found in breast milk at concentration similar to plasma.
Contraindications
Hypersensitivity to fluconazole or any component of the formulation (cross-reaction with other azole antifungal agents may occur, but has not been established; use caution); concomitant administration with cisapride or terfenadine
Warnings/Precautions
Concerns related to adverse effects:
• Skin reactions: Rare exfoliative skin disorders have been observed; monitor closely if rash develops and discontinue if lesions progress.
Disease-related concerns:
• Arrhythmias: The manufacturer reports rare cases of QTc prolongation and torsade de pointes associated with fluconazole use and advises caution in patients with concomitant medications or conditions which are arrhythmogenic. However, given the limited number of cases and the presence of multiple confounding variables, the likelihood that fluconazole causes conduction abnormalities appears remote.
• Hepatic impairment: Serious (and rarely fatal) hepatic toxicity (eg, hepatitis, cholestasis, fulminant failure) has been observed with azole therapy. Use with caution in patients with pre-existing hepatic impairment; monitor liver function closely and dosage adjustment may be warranted; discontinue if symptoms consistent with liver disease develop.
• Renal impairment: Use with caution in patients with renal impairment.
Adverse Reactions
Frequency not always defined.
Cardiovascular: Angioedema, pallor, QT prolongation (rare, case reports), torsade de pointes (rare, case reports)
Central nervous system: Headache (2% to 13%), dizziness (1%), seizure
Dermatologic: Rash (2%), alopecia, toxic epidermal necrolysis, Stevens-Johnson syndrome
Endocrine & metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia
Gastrointestinal: Nausea (2% to 7%), abdominal pain (2% to 6%), vomiting (2% to 5%), diarrhea (2% to 3%), dyspepsia (1%), taste perversion (1%)
Hematologic: Agranulocytosis, leukopenia, neutropenia, thrombocytopenia
Hepatic: Alkaline phosphatase increased, ALT increased, AST increased, cholestasis, hepatic failure (rare), hepatitis, jaundice
Respiratory: Dyspnea
Miscellaneous: Anaphylactic reactions (rare)
Metabolism/Transport Effects
Inhibits CYP1A2 (weak), 2C9 (strong), 2C19 (strong), 3A4 (moderate)
Drug Interactions
Alfentanil: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Alfentanil. Risk D: Consider therapy modification
Alfentanil: Fluconazole may decrease the metabolism of Alfentanil. Risk D: Consider therapy modification
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Aprepitant: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Aprepitant. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Benzodiazepines (metabolized by oxidation): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: The following combinations are specifically contraindicated: itraconazole with alprazolam, estazolam, oral midazolam, or triazolam; ketoconazole with alprazolam, estazolam, or triazolam. Consider initial dose reductions of other benzodiazepines. Exceptions: Quazepam. Risk D: Consider therapy modification
Benzodiazepines (metabolized by oxidation): Fluconazole may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Bosentan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Bosentan. Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
BusPIRone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Busulfan. Risk C: Monitor therapy
Calcium Channel Blockers: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
Calcium Channel Blockers: Fluconazole may decrease the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk C: Monitor therapy
CarBAMazepine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CarBAMazepine. Risk C: Monitor therapy
CarBAMazepine: Fluconazole may decrease the metabolism of CarBAMazepine. Risk C: Monitor therapy
Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cilostazol: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Cilostazol. Risk D: Consider therapy modification
Cinacalcet: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Cinacalcet. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cisapride: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cisapride. Risk X: Avoid combination
Citalopram: Fluconazole may increase the serum concentration of Citalopram. Risk C: Monitor therapy
Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk X: Avoid combination
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification
Conivaptan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Risk X: Avoid combination
Corticosteroids (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Corticosteroids (Systemic): Fluconazole may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
CycloSPORINE: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE: Fluconazole may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification
CycloSPORINE (Systemic): Fluconazole may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Didanosine: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. Risk D: Consider therapy modification
DOCEtaxel: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of DOCEtaxel. Risk D: Consider therapy modification
Dofetilide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Dofetilide. Risk X: Avoid combination
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Eletriptan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Eletriptan. Risk D: Consider therapy modification
Eletriptan: Fluconazole may decrease the metabolism of Eletriptan. Risk C: Monitor therapy
Eplerenone: Fluconazole may increase the serum concentration of Eplerenone. Management: Reduce the starting dose of eplerenone to 25 mg/day; monitor patients closely for increased eplerenone effects. Risk D: Consider therapy modification
Erlotinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Erlotinib. Risk C: Monitor therapy
Eszopiclone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Eszopiclone. Risk C: Monitor therapy
Etravirine: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Etravirine may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with voriconazole. Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Management: Monitor for increased effects/toxicity of etravirine. Antifungal dose adjustment may be needed for ketoconazole, itraconazole, or posaconazole but specific dosing guidelines are lacking. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Fosaprepitant: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosaprepitant. Specifically, concentrations of aprepitant are likely to be increased. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosphenytoin. Risk D: Consider therapy modification
Fosphenytoin: Fluconazole may increase the serum concentration of Fosphenytoin. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Gefitinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Gefitinib. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This specifically applies to oral antifungal administration, and the interaction may be different depending on specific dosage form being used. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider use of HMG-CoA reductase inhibitors posing the least rhabdomyolysis risk (e.g. fluva- or pravastatin), and monitor for signs/symptoms of rhabdomyolysis. Do not use keto- or itraconazole with lova- or simvastatin, or posaconazole with simvastatin. Exceptions: Fluvastatin; Pitavastatin; Rosuvastatin. Risk D: Consider therapy modification
HMG-CoA Reductase Inhibitors: Fluconazole may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Pitavastatin; Pravastatin; Rosuvastatin. Risk D: Consider therapy modification
Imatinib: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Imatinib. Risk C: Monitor therapy
Irbesartan: Fluconazole may decrease the metabolism of Irbesartan. Risk C: Monitor therapy
Irinotecan: Antifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Irinotecan. Risk D: Consider therapy modification
Losartan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Losartan. Risk C: Monitor therapy
Losartan: Fluconazole may decrease the metabolism of Losartan. Risk C: Monitor therapy
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification
Macrolide Antibiotics: May decrease the metabolism of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Macrolide Antibiotics. Exceptions: Azithromycin; Azithromycin (Systemic); Spiramycin. Risk D: Consider therapy modification
Methadone: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Methadone. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Phenytoin: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Risk D: Consider therapy modification
Phenytoin: Fluconazole may increase the serum concentration of Phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Pimozide. Risk X: Avoid combination
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Protease Inhibitors: May increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Protease Inhibitors. Management: Limit indinavir adult dose to 600 mg every 8 hours with itraconazole or ketoconazole. With ritonavir, limit ketoconazole adult dose to 200 mg/day. Limit fluconazole, itraconazole, and ketoconazole to 200 mg (adult dose) with tipranavir/ritonavir. Risk D: Consider therapy modification
Proton Pump Inhibitors: Fluconazole may increase the serum concentration of Proton Pump Inhibitors. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QuiNIDine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of QuiNIDine. Management: Itraconazole, voriconazole, and posaconazole are specifically contraindicated with quinidine. Use of quinidine with any azole antifungal may require quinidine dose adjustment and should be done with caution and close monitoring. Risk X: Avoid combination
QuiNIDine: Fluconazole may decrease the metabolism of QuiNIDine. Risk C: Monitor therapy
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Ramelteon: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ramelteon. Risk C: Monitor therapy
Ramelteon: Fluconazole may decrease the metabolism of Ramelteon. Risk C: Monitor therapy
Ranolazine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ranolazine. Risk X: Avoid combination
Repaglinide: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Repaglinide. Management: Concurrent use of an azole antifungal with both repaglinide and gemfibrozil should be avoided. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Risk D: Consider therapy modification
Rifamycin Derivatives: Fluconazole may decrease the metabolism of Rifamycin Derivatives. This appears only affect rifabutin. Rifamycin Derivatives may increase the metabolism of Fluconazole. Risk C: Monitor therapy
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sirolimus: Fluconazole may increase the serum concentration of Sirolimus. Management: Sirolimus dose adjustments will likely be needed when starting/stopping any azole antifungal. Clinical data suggest sirolimus (adult) dose reductions of 50-90% will be needed when starting an azole antifungal, but specific guidelines are lacking. Risk D: Consider therapy modification
Solifenacin: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Solifenacin. Risk D: Consider therapy modification
Sucralfate: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk C: Monitor therapy
Sulfonylureas: Fluconazole may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
SUNItinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of SUNItinib. Risk D: Consider therapy modification
Tacrolimus: Fluconazole may decrease the metabolism of Tacrolimus. Management: Monitor tacrolimus concentrations closely and adjust dose as necessary when concomitantly administered with fluconazole. Reduced doses of fluconazole will likely be required. Risk D: Consider therapy modification
Tacrolimus (Systemic): Fluconazole may decrease the metabolism of Tacrolimus (Systemic). Management: Monitor tacrolimus concentrations closely and adjust dose as necessary when concomitantly administered with fluconazole. Reduced doses of fluconazole will likely be required. Risk D: Consider therapy modification
Tacrolimus (Topical): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy
Tacrolimus (Topical): Fluconazole may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy
Temsirolimus: Fluconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to fluconazole. Monitor sirolimus concentrations in all patients receiving fluconazole or any systemic azole antifungal. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tolterodine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tolterodine. This is likely only of concern in CYP2D6-deficient patients (ie, "poor metabolizers") Risk D: Consider therapy modification
Tolterodine: Fluconazole may decrease the metabolism of Tolterodine. This is likely only of concern in CYP2D6-deficient patients (ie, "poor metabolizers") Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Fluconazole may increase the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification
Voriconazole: Fluconazole may increase the serum concentration of Voriconazole. Risk X: Avoid combination
Zidovudine: Fluconazole may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ziprasidone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ziprasidone. Risk C: Monitor therapy
Zolpidem: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Zolpidem. Management: Consider using a lower starting dose of zolpidem in patients receiving systemic azole antifungals. Monitor patients closely for increased magnitude and/or duration of zolpidem effects when using this combination. Risk D: Consider therapy modification
Storage
Tablet: Store at <30°C (86°F).
Powder for oral suspension: Store dry powder at <30°C (86°F). Following reconstitution, store at 5°C to 30°C (41°F to 86°F). Discard unused portion after 2 weeks. Do not freeze.
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). Do not freeze. Do not unwrap unit until ready for use.
Compatibility
Stable 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 calcium, 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 Action
Interferes with fungal cytochrome P450 activity (lanosterol 14-α-demethylase), decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation
Pharmacodynamics/Kinetics
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)
Dosage
The daily dose of fluconazole is the same for oral and I.V. administration
Usual dosage ranges:
Neonates: First 2 weeks of life, especially premature neonates: Same dose as older children every 72 hours
Children: Loading dose: 6-12 mg/kg; maintenance: 3-12 mg/kg/day; duration and dosage depends on severity of infection
Adults: 150 mg once or 200-800 mg/day; duration and dosage depends on severity of infection
Indication-specific dosing:
Children:
Candidiasis:
Oropharyngeal:
Manufacturer's recommendation: Loading dose: 6 mg/kg; maintenance: 3 mg/kg/day once daily for 2 weeks
HIV-exposed/-positive: 3-6 mg/kg/day once daily (maximum: 400 mg/day) (CDC, 2009)
Esophageal:
Manufacturer's recommendation: Loading dose: 6 mg/kg; maintenance: 3-12 mg/kg/day once daily for 21 days and at least 2 weeks following resolution of symptoms
HIV-exposed/-positive: Loading dose: 6 mg/kg once on day 1; maintenance: 3-6 mg/kg/day once daily (maximum: 400 mg/day) (CDC, 2009)
Relapse suppression (HIV-exposed/-positive): 3-6 mg/kg/day once daily (maximum: 200 mg/day) (CDC, 2009)
Invasive disease (independent of HIV status): 5-6 mg/kg every 12 hours for 28 days (maximum: 600 mg/day) (CDC, 2009)
Coccidioidomycosis (CDC, 2009):
Meningeal and disseminated disease (HIV-exposed/-positive): 5-6 mg/kg/dose every 12 hours (maximum: 800 mg/day)
Relapse suppression (HIV-exposed/-positive): 6 mg/kg/day once daily (maximum: 400 mg/day)
Histoplasmosis, relapse suppression (HIV-exposed/-positive): 3-6 mg/kg/day once daily (maximum: 200 mg/day) (CDC, 2009)
Cryptococcal disease (CDC, 2009):
Meningitis (consolidation): Loading dose: 12 mg/kg once on day 1; maintenance: 6-12 mg/kg/day once daily for a minimum of 8 weeks (maximum: 800 mg/day)
Disseminated (non-CNS) or severe pulmonary disease: Loading dose: 12 mg/kg once on day 1; maintenance: 6-12 mg/kg/day once daily (maximum: 600 mg/day)
Relapse suppression (HIV-exposed/-positive): 6 mg/kg/day once daily (maximum: 200 mg/day)
Adults:
Candidiasis (Pappas, 2009):
Candidemia (neutropenic and non-neutropenic): Loading dose: 800 mg on first day, then 400 mg/day for 14 days after first negative blood culture and resolution of signs/symptoms; Note: Not recommended for neutropenic patients with recent azole exposure and critical illness
Chronic, disseminated: 400 mg/day until calcification or lesion resolution
CNS candidemia: 400-800 mg/day until CSF/radiological abnormalities resolved; Note: Recommended as alternative therapy in patients intolerant of amphotericin B
Oropharyngeal: 100-200 mg/day for 7-14 days for uncomplicated, moderate-to-severe disease; chronic therapy of 100 mg 3 times weekly is recommended in immunocompromised patients with history of oropharyngeal candidiasis (OPC)
Osteoarticular: 400 mg/day for 6-12 months (osteomyelitis) or 6 weeks (septic arthritis)
Esophageal: 200-400 mg/day for 14-21 days
Prophylaxis:
Solid organ: 200-400 mg/day for 7-14 days
Neutropenic patients: 400 mg/day for duration of neutropenia
Urinary tract:
Fungus balls: 200-400 mg/day
Pyelonephritis: 200-400 mg/day for 2 weeks
Symptomatic cystitis: 200 mg/day for 2 weeks
Vaginal:
Uncomplicated: 150 mg as a single dose
Complicated: 150 mg every 72 hours for 3 doses
Recurrent: 150 mg daily for 10-14 days, followed by 150 mg once weekly for 6 months
Candidal intertrigo (unlabeled use; Coldiron, 1991; Nozickova, 1998; Stengel, 1994): 50 mg/day or 150 mg once weekly
Coccidiomycosis (unlabeled use; Galgiani, 2005): 400-800 mg/day; doses of 800-1000 mg/day have been used for meningeal disease; usual duration of therapy ranges from 3-6 months for primary uncomplicated infections and up to 1 year for pulmonary (chronic and diffuse) infection
Endocarditis, prosthetic valve, early (unlabeled use; Pappas, 2009): 400-800 mg/day for 6 weeks after valve replacement (as step-down in stable, culture-negative patients); long-term suppression in absence of valve replacement: 400-800 mg/day
Endophthalmitis (Pappas, 2009): 400-800 mg/day for 4-6 weeks until examination indicates resolution
Meningitis, cryptococcal (Perfect, 2010):
Induction therapy: Typically consists of an amphotericin product and flucytosine for 2-6 weeks
Consolidation therapy: Fluconazole 400-800 mg/day for 8 weeks
Maintenance therapy: 200 mg/day for 6-12 months (post-transplant patients; non-HIV infected patients) or ≥1 year (HIV-infected patients may require lifelong therapy; CDC, 2009)
Pericarditis or myocarditis (Pappas, 2009): 400-800 mg/day
Pneumonia, cryptococcal (mild-to-moderate) (unlabeled use; Perfect, 2010): 400 mg/day for 6-12 months (HIV-infected patients may require lifelong therapy; CDC, 2009)
Dosing adjustment/interval in renal impairment:
No adjustment for vaginal candidiasis single-dose therapy
For multiple dosing, administer usual load then adjust daily doses as follows:
Clcr ≤50 mL/minute (no dialysis): Administer 50% of recommended dose or administer every 48 hours.
Hemodialysis: 50% is removed by hemodialysis; administer 100% of daily dose (according to indication) after each dialysis treatment.
Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:
CVVH: 200-400 mg every 24 hours
CVVHD/CVVHDF: 400-800 mg every 24 hours
Note: Higher daily doses of 400 mg (CVVH) and 800 mg (CVVHD/CVVHDF) should be considered when treating resistant organisms and/or when employing combined ultrafiltration and dialysis flow rates of ≥2 L/hour for CVVHD/CVVHDF (Trotman, 2005).
Dental Usual Dosing
Candidiasis: Adults:
Usual dosage range: 200-400 mg/day; duration and dosage depends on severity of infection
Oropharyngeal (long-term suppression): 200 mg/day; chronic therapy is recommended in immunocompromised patients with history of oropharyngeal candidiasis (OPC)
Administration: Oral
May be administered without regard to meals.
Administration: I.V.
Do not use if cloudy or precipitated. Infuse over approximately 1-2 hours; do not exceed 200 mg/hour.
Administration: I.V. Detail
pH: 4-8 (sodium chloride diluent); 3.5-6.5 (dextrose)
Monitoring Parameters
Periodic liver function tests (AST, ALT, alkaline phosphatase) and renal function tests, potassium
Dietary Considerations
Take without regard to meals.
Patient Education
Frequent blood tests may be required. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause headache, dizziness, drowsiness, nausea, vomiting, or diarrhea. Report skin rash, persistent GI upset, urinary pattern changes, excessively dry eyes or mouth, or changes in color of stool or urine.
Geriatric Considerations
Has not been specifically studied in the elderly.
Cardiovascular Considerations
Fluconazole is contraindicated in patients taking cisapride due to increased risk for significant cardiotoxicity, particularly proarrhythmia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Abnormal taste.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness and seizures
Mental Health: Effects on Psychiatric Treatment
None reported; CYP3A4 inhibitor; use caution with triazolam, alprazolam, and midazolam
Nursing: Physical Assessment/Monitoring
Assess results of cultures/sensitivity and patient's allergy history prior to beginning therapy. Assess renal and hepatic function. Monitor for hepatotoxicity (jaundice), skin disorders, and abdominal pain on a regular basis.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion, premixed iso-osmotic dextrose solution: 200 mg (100 mL); 400 mg (200 mL)
Diflucan®: 400 mg (200 mL)
Infusion, premixed iso-osmotic sodium chloride solution: 100 mg (50 mL); 200 mg (100 mL); 400 mg (200 mL)
Diflucan®: 200 mg (100 mL); 400 mg (200 mL)
Infusion, premixed iso-osmotic sodium chloride solution [preservative free]: 200 mg (100 mL); 400 mg (200 mL)
Powder for suspension, oral: 10 mg/mL (35 mL); 40 mg/mL (35 mL)
Diflucan®: 10 mg/mL (35 mL); 40 mg/mL (35 mL) [contains sodium benzoate; orange flavor]
Tablet, oral: 50 mg, 100 mg, 150 mg, 200 mg
Diflucan®: 50 mg, 100 mg, 150 mg, 200 mg
Pricing: U.S. (www.drugstore.com)
Suspension (reconstituted) (Diflucan)
10 mg/mL (35): $55.99
40 mg/mL (35): $190.99
Suspension (reconstituted) (Fluconazole)
10 mg/mL (35): $27.99
40 mg/mL (35): $109.98
Tablets (Diflucan)
50 mg (15): $129.99
100 mg (30): $393.99
150 mg (1): $31.99
200 mg (4): $93.99
Tablets (Fluconazole)
50 mg (15): $49.99
100 mg (15): $54.99
150 mg (12): $49.99
200 mg (4): $39.77
References
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, "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.
Centers for Disease Control and Prevention, “Guidelines for Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Adults and Adolescents. Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, MMWR Recomm Rep, 2009, 58(RR-4):1-207.
Centers for Disease Control and Prevention, “Guidelines for Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children. Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166.
Centers for Disease Control and Prevention (CDC), "Sexually Transmitted Diseases Treatment Guidelines, 2010," MMWR Recomm Rep, 2010, 59(RR-12):1-110.
Coldiron BM and Manders SM, "Persistent Candida Intertrigo Treated With Fluconazole," Arch Dermatol, 1991, 127(2):165-6.
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.
Galgiani JN, Ampel NM, Blair JE, et al, “Coccidioidomycosis,” Clin Infect Dis, 2005, 41(9):1217-23.
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.
Nozickova M, Koudelkova V, Kulikova Z, et al, "A Comparison of the Efficacy of Oral Fluconazole, 150 mg/week Versus 50 mg/day, in the Treatment of Tinea Corporis, Tinea Cruris, Tinea Pedis, and Cutaneous Candidosis," Int J Dermatol, 1998, 37(9):703-5.
Pappas PG, Kauffman CA, Andes D, et al, “Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2009, 48(5):503-35.
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.
Perfect JR, Dismukes WE, Dromer F, et al, “Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2010, 50(3):291-322.
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.
Pham CP, de Feiter PW, van der Kuy PH, “Long QTc Interval and Torsade de Pointes Caused by Fluconazole,” Ann Pharmacother, 2006, 40(7):1456-61.
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.
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.
Stengel F, Robles-Soto M, Galimberti R, et al, "Fluconazole Versus Ketoconazole in the Treatment of Dermatophytoses and Cutaneous Candidiasis," Int J Dermatol, 1994, 33(10):726-9.
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.
Trotman RL, Williamson JC, Shoemaker DM, et al, “Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy,” Clin Infect Dis, 2005, 41(8):1159-66.
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.
Wassmann S, Nickenig G, and Bohm M, “Long QT Syndrome and Torsade de Pointes in a Patient Receiving Fluconazole,” Ann Inter Med, 1999, 131(10):797.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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