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Medication Safety Issues
Sound-alike/look-alike issues:
Fluconazole may be confused with flecainide
Diflucan® may be confused with diclofenac, Diprivan®, disulfiram
International issues:
Canesten® [Great Britain]: Brand name for clotrimazole in multiple international markets
Pronunciation
(floo KOE na zole)
U.S. Brand Names
Generic Available
Yes
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
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/not recommended (AAP rates “compatible”)
Breast-Feeding Considerations
Fluconazole is found in breast milk at concentration similar to plasma.
Contraindications
Hypersensitivity to fluconazole, other azoles, or any component of the formulation; concomitant administration with cisapride
Warnings/Precautions
Concerns related to adverse effects:
• Skin reactions: Rare exfoliative skin disorders have been observed; monitor closely if rash develops.
Disease-related concerns:
• Arrhythmias: The manufacturer reports rare cases of QTc prolongation and TdP 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%), 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
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
Antacids: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
Aprepitant: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Aprepitant. Risk C: Monitor therapy
Benzodiazepines (metabolized by oxidation): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). 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
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. Risk D: Consider therapy modification
Calcium Channel Blockers: Fluconazole may decrease the metabolism of Calcium Channel Blockers. 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
Cardiac Glycosides: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification
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
Cisapride: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cisapride. Risk X: Avoid combination
Conivaptan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Risk X: Avoid combination
Corticosteroids (Orally Inhaled): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Corticosteroids (Orally Inhaled). Exceptions: Beclomethasone; Flunisolide; Triamcinolone. Risk C: Monitor therapy
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
Coumarin Derivatives: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Coumarin Derivatives. Risk D: Consider therapy modification
Coumarin Derivatives: Fluconazole may decrease the metabolism of Coumarin Derivatives. Risk D: Consider therapy modification
CycloSPORINE: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE: Fluconazole may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP2C9 Substrates (High risk with Highly Effective Inhibitors): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inhibitors). 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
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: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Eplerenone. Risk D: Consider therapy modification
Eplerenone: Fluconazole may decrease the metabolism of Eplerenone. Risk C: Monitor therapy
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
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
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 metabolism of Antifungal Agents (Azole Derivatives, Systemic). This specifically applies to oral antifungal administration. Risk D: Consider therapy modification
H2-Antagonists: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
HMG-CoA Reductase Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Fluvastatin; Rosuvastatin. Risk D: Consider therapy modification
HMG-CoA Reductase Inhibitors: Fluconazole may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Pravastatin; Rosuvastatin. Risk D: Consider therapy modification
Imatinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism 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
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; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors may increase the serum concentration of Maraviroc. 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: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
Phenytoin: Fluconazole may decrease the metabolism 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
Protease Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Limit indinavir to 600mg every 8 hours with itraconazole or ketoconazole. When used with ritonavir, limit ketoconazole to 200mg/day. Tipranavir labeling recommends limiting fluconazole, itraconazole, and ketoconazole to 200mg with tipranavir/ritonavir. Risk D: Consider therapy modification
Proton Pump Inhibitors: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
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
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
Rifamycin Derivatives: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). 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
Sirolimus: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Sirolimus. Management: Sirolimus dose reductions of up to 50-90% may be necessary when starting an azole antifungal. Use of sirolimus with the azole antifungals voriconazole and posaconazole is contraindicated. 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: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus. Risk D: Consider therapy modification
Tacrolimus: Fluconazole may decrease the metabolism of Tacrolimus. Risk D: Consider therapy modification
Temsirolimus: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Temsirolimus. Concentrations of the active metabolite, sirolimus, are likely to be increased more substantially than those of the parent temsirolimus. Risk D: Consider therapy modification
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
VinCRIStine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of VinCRIStine. Risk D: Consider therapy modification
Zidovudine: Fluconazole may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Ziprasidone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ziprasidone. Risk C: Monitor therapy
Zolpidem: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Zolpidem. Risk D: Consider therapy modification
Storage
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, 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-?-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: 200-800 mg/day; duration and dosage depends on severity of infection
Indication-specific dosing:
Children:
Candidiasis:
Oropharyngeal: Loading dose: 6 mg/kg; maintenance: 3 mg/kg/day for 2 weeks
Esophageal: Loading dose: 6 mg/kg; maintenance: 3-12 mg/kg/day for 21 days and at least 2 weeks following resolution of symptoms
Systemic infection: 6 mg/kg every 12 hours for 28 days
Meningitis, cryptococcal: Loading dose: 12 mg/kg; maintenance: 6-12 mg/kg/day for 10-12 weeks following negative CSF culture; relapse suppression (HIV-positive): 6 mg/kg/day
Adults:
Candidiasis:
Candidemia (neutropenic and non-neutropenic): 400-800 mg/day for 14 days after last positive blood culture and resolution of signs/symptoms
Chronic, disseminated: 400-800 mg/day for 3-6 months
Oropharyngeal (long-term suppression): 200 mg/day; chronic therapy is recommended in immunocompromised patients with history of oropharyngeal candidiasis (OPC)
Osteomyelitis: 400-800 mg/day for 6-12 months
Esophageal: 200 mg on day 1, then 100-200 mg/day for 2-3 weeks after clinical improvement
Prophylaxis in bone marrow transplant: 400 mg/day; begin 3 days before onset of neutropenia and continue for 7 days after neutrophils >1000 cells/mm3
Urinary: 200 mg/day for 1-2 weeks
Vaginal: 150 mg as a single dose
Coccidiomycosis (unlabeled use, IDSA guideline): 400 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, IDSA guideline): 400-800 mg/day for 6 weeks after valve replacement; long-term suppression in absence of valve replacement: 200-400 mg/day
Endophthalmitis: 400-800 mg/day for 6-12 weeks after surgical intervention.
Meningitis, cryptococcal: Amphotericin 0.7-1 mg/kg +/- 5-FC for 2 weeks then fluconazole 400 mg/day for at least 10 weeks (consider life-long in HIV-positive); maintenance (HIV-positive): 200-400 mg/day life-long
Pneumonia, cryptococcal (mild-to-moderate) (unlabeled use, IDSA guideline): 200-400 mg/day for 6-12 months (consider life-long in HIV-positive patients)
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 with or without food.
Administration: I.M.
For I.V. only; do not administer I.M. or SubQ
Administration: I.V.
Infuse over approximately 1-2 hours.
Administration: I.V. Detail
Do not use if cloudy or precipitated. Do not exceed 200 mg/hour when administering by I.V. infusion.
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 with or without regard to food.
Patient Education
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.
Geriatric Considerations
Has not been specifically studied in the elderly.
Anesthesia and Critical Care Concerns/Other Considerations
Do not use if cloudy or precipitated. If administered by I.V. infusion, give over 1-2 hours.
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 potential for interactions with other pharmacological agents patient may be taking (eg, potential for toxicities). See Administration specifics for I.V. use. Assess results of laboratory tests (renal and hepatic function), therapeutic effectiveness (resolution of fungal infection), and adverse response (eg, hepatotoxicity [jaundice], skin disorders, abdominal pain) on a regular basis throughout therapy. Teach patient use (full course of therapy may require weeks or months after symptoms resolve), possible side effects/appropriate interventions, and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion [premixed in sodium chloride or dextrose]: 200 mg (100 mL); 400 mg (200 mL)
Diflucan® [premixed in sodium chloride or dextrose]: 200 mg (100 mL); 400 mg (200 mL)
Powder for oral suspension: 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: 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): $45.53
40 mg/mL (35): $157.16
Suspension (reconstituted) (Fluconazole)
10 mg/mL (35): $25.99
40 mg/mL (35): $109.98
Tablets (Diflucan)
50 mg (15): $109.99
100 mg (15): $171.86
150 mg (1): $25.99
200 mg (4): $76.37
Tablets (Fluconazole)
100 mg (15): $54.99
150 mg (12): $167.19
200 mg (4): $39.77
References
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“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.
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International Brand Names
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Last full review/revision August 2008
Content last modified August 2008
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