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 Fluconazole 

Uses of Fluconazole

Antifungal prophylaxis in pts undergoing bone marrow transplant; candidiasis(esophageal, oropharyngeal, urinary tract, vaginal); systemic Candida infections(e.g., candidemia); treatment of cryptococcal meningitis. 

OFF-LABEL: Cryptococcal pneumonia, candidal intertrigo.

CLINICAL: Systemic antifungal. 

Precautions of Fluconazole

Contraindications: Hypersensitivity to fluconazole. Concomitant administration of QT-prolonging medications (e.g., erythromycin, pimozide).

Cautions: Hepatic/renal impairment, hypokalemia, hypersensitivity to other triazoles (e.g., itraconazole, terconazole), imidazoles (e.g., butoconazole, ketoconazole). Medications or conditions are known to cause arrhythmias.

D-Dimer: Test Overview, Indication, Normal Value, Nursing Assessment

Action of Fluconazole

Interferes with cytochrome P-450 activity, an enzyme necessary for ergosterol formation. 

Therapeutic Effect: Directly damages the fungal membrane, altering its function. Fungistatic.

Pharmacokinetics of Fluconazole

Well absorbed from GI tract. Widely distributed, including to CSF. Protein binding: 11%. Partially metabolized in the liver. Excreted unchanged primarily in the urine. Partially removed by hemodialysis. Half-life: 20–30 hrs (increased in renal impairment). 

Lifespan considerations

Pregnancy/Lactation: Secreted in human breast milk. Use caution in breastfeeding females. Children: No age-related precautions were noted. Elderly: Age-related renal impairment may require dosage adjustment.

Interactions of Fluconazole

DRUG: Increases concentration/effect of calcium channel blockers (e.g., amlodipine, nifedipine, verapamil), celecoxib, cyclosporine, midazolam, methadone, NSAIDs (e.g., ibuprofen, ketorolac, naproxen), rifabutin, sirolimus, tacrolimus, theophylline, tofacitinib, zidovudine. May increase concentration/effect, risk of myopathy of HMG-CoA reductase inhibitors (e.g. atorvastatin, simvastatin). HCTZ may increase concentration/effect. Cimetidine, rifampin may decrease concentration/effect. May increase concentration/effect of oral hypoglycemics (e.g., glipizide, glyburide), phenytoin. May further prolong the prothrombin time of warfarin. Quinidine may increase QT prolongation; risk of torsades de pointes. HERBAL: None significant. FOOD: None known. LAB VALUES: May increase serum alkaline phosphatase, bilirubin, ALT, AST.

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Availability (Rx) of Fluconazole

Injection, Solution, Pre-Mix: 100 mg (50 mL), 200 mg (100 mL), 400 mg (200mL). 

Powder for Oral Suspension: 10 mg/mL, 40 mg/mL. 

Tablets: 50 mg, 100mg, 150 mg, 200 mg.

Administration/handling of Fluconazole

IV

Rate of Administration

• Do not exceed the maximum flow rate of 200 mg/hr.

Storage

• Store at room temperature.

• Do not remove from outer wrap until ready to use.

• Squeeze inner bag to check for leaks.

• Do not use the parenteral form if solution is cloudy, precipitate forms, seal is not intact, or it is discolored.

• Do not add supplementary medication.

PO

• Give without regard to meals.

IV incompatibilities of Fluconazole

Amphotericin B (Fungizone), amphotericin B complex (Abelcet, AmBisome, Amphotec), ampicillin (Polycillin), calcium gluconate, cefotaxime (Claforan), cefTRIAXone (Rocephin), cefuroxime (Zinacef), chloramphenicol

(Chloromycetin), clindamycin (Cleocin), co-trimoxazole (Bactrim), diazePAM (Valium), digoxin (Lanoxin), erythromycin (Erythrocin), furosemide (Lasix), haloperidol (Haldol), hydrOXYzine (Vistaril), imipenem and cilastatin

(Primaxin).

IV Compatibilities

Dexmedetomidine (Precedex), diltiaZEM (Cardizem), DOBUTamine (Dobutrex), DOPamine (Intropin), heparin, lipids, LORazepam (Ativan),

midazolam (Versed), propofol (Diprivan).

Indications/routes/dosage of Fluconazole

PO and IV therapy equally effective; IV therapy is recommended for pt intolerant of drug or unable to take orally. Oral suspension stable for 14 days at room temperature or refrigerated. 

Usual Dosage

Note: Duration and dose-dependent on location/severity of infection.

PO/IV: ADULTS, ELDERLY: 150 mg once or loading dose: 200–800 mg.

Maintenance dose: 200–800 mg once daily. CHILDREN AND NEONATES:

Loading dose: 6–12 mg/kg. Maintenance dose: 3–12 mg/kg once daily.

Maximum: 600 mg/day.

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Dosage in Renal Impairment

After a loading dose of 400 mg, daily dosage is based on creatinine clearance. 

Creatinine Clearance         Dosage

Greater than 50 mL/min:     100%

50 mL/min or less:               50%

Dialysis:                              50%

CCRT:                                 400–800 mg as loading dose

CVVH:                                then 200–800 mg/day

CVVHDF:                           400–800 mg as loading dose, then 400–800 mg/day 

Dosage in Hepatic Impairment

Use caution 

Side effects of Fluconazole

Occasional (4%–1%): Hypersensitivity reaction (chills, fever, pruritus, rash), dizziness, drowsiness, headache, constipation, diarrhea, nausea, vomiting, abdominal pain. 

Adverse effects/toxic reactions

Exfoliative skin disorders, serious hepatic injury, blood dyscrasias (eosinophilia, thrombocytopenia, anemia, leukopenia) have been reported rarely. May increase risk of QT prolongation, torsades de pointes. Skin disorders including Stevens-Johnson syndrome, toxic epidermal necrolysis may occur. 

Nursing considerations of Fluconazole

Baseline assessment

Obtain CBC, LFT; serum potassium in critically ill pts. Receive full medication history and screen for interactions. Assess areas of infection. Assess infected area.

Intervention/evaluation

Assess for hypersensitivity reaction (chills, fever). Monitor CBC, BMP, LFT. Report rash, itching promptly. Monitor temperature at least daily. Monitor daily pattern of bowel activity, stool consistency. Assess for dizziness; provide

assistance as needed.

Patient/family teaching

• Report dark urine, pale stool, jaundiced skin or sclera of eyes, rash, pruritus.

• Pts with oropharyngeal infections should maintain fastidious oral hygiene.

• Consult a physician before taking any other medication.