University of Maryland Medical Center

Fluconazole (Diflucan®)
Guidelines for Use

BACKGROUND

• These recommendations are to be utilized for the appropriate treatment of

Candida infections with fluconazole. Please contact Infectious Diseases via
BUGS or pharmacy for assistance.
• Spectrum of activity:
✔Fluconazole will treat the following Candida species: C. albicans, C.
parapsilosis, C. tropicalis and C. lusitaniei.
✔The following Candida species are resistant to fluconazole; C. krusei and
C. glabrata (some C. glabrata may be treatable at higher doses but should
be discussed with ID).
• Colonization of non-sterile sites (ie sputum, urine in drainage catheters and
wounds) with Candida is common and does not warrant therapy. The best
treatment of Candida colonization is removing foreign bodies such as urinary
catheters and reducing or stopping broad-spectrum antibiotics where
appropriate.
• Fluconazole has excellent oral bioavailability and should be given orally in all
patients who are taking other oral medications or naso-gastric feedings.
• Fluconazole dosing needs adjustment for severe liver and/or renal
dysfunction.

INDICATIONS

Non-Transplant Patients

• Blood Stream Infection (BSI)

a. Remove intravascular devices including dialysis catheters.
b. If endocarditis- CT surgery and ID consults and continue therapy.
c. Endovascular grafts – continue therapy and monitor blood cultures.
d. Narrow spectrum or stop antibiotics if possible
e. Convert parenteral to enteral nutrition where possible

• Urinary Tract Infections.

*Note: Fluconazole therapy has NOT been shown to have either clinical or long-
term microbiological benefit in treating Candida UTI.
a. Needs urinalysis as proof
b. Remove foley as primary therapy
c. Do not treat colonization
d. Remove urinary stents or drainage devices where possible
 e. If systemic infection suspected (i.e. large number white cells in UA and
febrile) treat as per BSI.

• Sputum
a. No treatment indications
b. Reduce broad spectrum antibiotics
c. Encourage enteral feeding

• Esophagitis
a. Only in HIV and other immunocompromised patients.
b. Refer to dosage section for treatment regimen
• Wound
a. No therapy required
b. Reduce broad spectrum antibiotics
c. Use enteral feeding where possible

• CNS
a. Remove intraventricular catheter
b. Use BSI dosing

• PD catheter Infection
a. Remove PD catheter
b. Refer to dosage section for treatment regimen

Transplant Patients (Solid Organs)

Fluconazole should be used with caution due to possible interactions with immune
suppressive agents. Please contact Infectious Diseases and transplant pharmacist
prior to using fluconazole. Exception is for liver transplant patients, which can be
found in the prophylaxis guidelines.

Cryptococcal Meningitis

a. Induction with amphotericin B for 2 weeks.

b b. Continue with Fluconazole for 2 months.
c. Maintenance therapy in HIV patients with CD4 T cell ≤ 200.

Note: Please refer to appendix I for empiric indications in SICU

DOSAGE AND ADMINISTRATION

Adult Dosage

*Note: same dose for both PO and IV

• Blood Stream Infection (BSI)
✑ ✔Fluconazole load – 800 mg X 1, then 400 mg once a day for 14 days.

• Esophagitis
✔New patients only require Fluconazole 200 mg/day
✔In HIV patient with repeated infection, will need BSI dosing

• PD catheter Infection
✔Fluconazole 400mg/day

• Cryptococcal Meningitis
✔Induction: Amphotericin B. 0.7-1 mg/kg/day for 2 weeks, then Fluconazole
400mg/day x 2 months
✔Maintenance treatment: Fluconazole 200mg/day (for HIV patients with CD4 T
cell ≤ 200)

• Allogenic bone marrow transplant

✔Fluconazole 400mg/ day (prophylaxis dose)

Pediatric Dosage

*Note: same dose for both PO and IV

***Consult Pediatric Infectious Disease Service for Treatment of Disseminated

Fungal Infections***

Premature Neonates:

≤ 29 weeks gestation:
Postnatal age 0-14 days: 5-6 mg/kg/ dose Q72H
Postnatal age >14 days: 5-6 mg/kg/dose Q48H
30-36 weeks gestation:
Postnatal age 0-14 days: 6mg/kg/dose Q48H

Neonates > 14 days, Infants and Children: Dose Frequency is Q24H

Oropharyngeal Candidiasis
6 mg/kg/day on day #1, 3 mg/kg/day for 14 days
Esophageal Candidiasis
6 mg/kg/day on day #1, 3-6 mg/kg/day for 21 days (For serious or
recurrent infection, may increase dose to 12mg/kg/day)
Systemic Candidiasis
Loading dose: 12mg/kg/day, then 6 mg/kg/day for 28 days
 Cryptococcal Meningitis
Acute
12 mg/kg/day on day #1, 6-12 mg/kg/day for 10-12 wk after CSF culture
becomes negative
Relapse
6 mg/kg/day

Dosage Adjustment in Renal Impairment

GFR 50-80 ml/min ➔ usual dose

GFR 10-50 ml/min ➔ 50% of usual dose
GFR <10 ml/min ➔ 25-50 mg/day
Hemo ➔ Dose after dialysis
CAPD ➔ 50% of the usual dose
CAVH ➔ 50% of the usual dose

ADVERSE EFFECTS

GI - Bloating, nausea, vomiting, pain, anorexia, weight loss (dose related)

CNS - headache
Dermatologic - Rash
Misc - Reversible alopecia (dose related)
Laboratory - Transaminase elevation to > 8x normal (1%)
Prolonged prothrombin time with warfarin
Hypokalemia (<1%)

PREGNANCY CATEGORY

Pregnancy category C

MONITORING

Periodic liver function tests (AST, ALT, alkaline phosphatase), renal function (Scr,
BUN) & potassium.
DRUG INTERACTIONS

Mechanism: inhibit cytochrome P-450

Alprazolam Increased sedation

Atovaquone Increased atovaquone levels
Benzodiazepines Increased benzodiazepines levels
Caffeine Possible caffeine toxicity
Cisapride* Ventricular arrhythmias
Clarithromycin Increased clarithromycin levels
Contraceptive Decreased contraceptive effect
Coumadin Increased prothrombin time
Cyclosporine Increased Cyclosporine nephrotoxicity
Midazolam Increased sedation
Nortriptyline increased sedation, cardiac arrhythmias
Phenytoin Increased phenytoin levels
Rifabutin* Increased rifabutin levels with possible uveitis
Rifampin Reduced fluconazole absorption
Saquinavir Increased saquinavir levels
Seldane* Ventricular arrhythmias
Sulfonylureas Increased levels with hypoglycemia
Tacrolimus Increased nephrotoxicity
Theophylline Increased levels of theophylline
Triazolam Increased sedation
Zidovudine Increased levels of zidovudine
* Concurrent use should be avoided

STORAGE

Oral Form: Store below 30 degree Celsius

Parenteral Form: Store glass bottle between 30 degree and 5 degree Celsius

AVAILABILITY

Injection: 2 mg/ml (100 ml, 200 ml)

Tablet: 50 mg, 100 mg, 150 mg, 200 mg
Powder for Oral Suspension: 10 mg/ml (35 ml), 40 mg/ml (35 ml)

The IV Formulation require approval from Infectious Disease Service

Two prophylactic indications that are EXEMPT from ID approval include
Post-operative liver transplant patients and allogenic bone marrow transplant
patients
Revised April, 2002
 Appendix I. Fluconazole Guidelines for Empiric Use in SICU.

Class 1: Demonstrated reduction in Candidal colonization with resultant decrease in

candidemia.
NOTE: Studies have not shown any survival benefit from empiric fluconazole usage,
only a reduction in candidemia.
Class 2: Case reports demonstrating benefit, but needs further study to reach Class 1.
Empiric fluconazole should only be implemented after evaluating the following risk
factors that can be reduced:
1) Reduce or stop broad-spectrum antibiotics
2) Remove intravascualar and urinary devices where possible
3) Early use of GI tract where possible and less parenteral nutrition
4) drainage of intra-abdominal collections
Class 1 Indication Risk Factors
A Liver or Pancreatic > 2 Risk re-transplantation
Transplantation factors Cr > 2.0
Cholangio-jejunostomy
> 40 units blood loss
Positive culture for Candida < 72 hours of Transplant

B Must have
these
High Risk SICU 2 risk Febrile
patient factors: > 72 hours in ICU

With one 2 or more abdominal surgeries

of persistent entero-cutaneous fistula
> 2 sites of Candidal colonization
Prolonged treatment with broad spectrum antibiotics
Hyperalimentation
Hemodialysis
Corticosteroid and/or Immunosuppressive therapy
Undrained intra-abdominal collection

Class 2
Necrotizing
Pancreatitis Must meet criteria in Class1 B
Cirrhosis with Transplant listed with positive culture-near surgery
ascites And must meet one of the criteria in Class 1B
Initial GI > 72 hours in ICU
Perforation and must meet one of the criteria in Class 1B
References:
1) Pelz RK et al. Double-blinded Placebo Controlled Trial of Fluconazole to Prevent
Candidal Infections in Critically Ill Surgical Patients. Ann of Surg. 2001;233:542-8.
2) Rex JH, Sobel, JD. Prohylactic Antifungal Therapy in the ICU. CID 2001;32:1191-
1200.