How do I dose, prepare, and infuse intravenous fluconazole (including loading and maintenance doses, renal dose adjustments, pediatric dosing, and criteria for switching to oral therapy)?

Intravenous Fluconazole Administration Guide

For most invasive candidiasis and candidemia, administer IV fluconazole as an 800 mg loading dose on day 1, followed by 400 mg daily, infused at a maximum rate of 200 mg/hour; switch to oral therapy as soon as the patient can tolerate oral intake, as both routes are therapeutically equivalent. 1, 2, 3

Standard Dosing by Indication

Candidemia and Invasive Candidiasis

• Loading dose: 800 mg (12 mg/kg) IV on day 1 1, 2
• Maintenance dose: 400 mg (6 mg/kg) IV daily 1, 2
• Duration: Continue for at least 14 days after the first negative blood culture and resolution of symptoms 1, 2
• Critical action: Remove all intravascular catheters if possible 1

Esophageal Candidiasis

• Dose: 200-400 mg (3-6 mg/kg) IV daily for 14-21 days 1
• Alternative for moderate-severe disease: 400 mg IV daily 1
• When oral intake impossible: IV route is required; switch to oral as soon as swallowing is feasible 1, 4

Oropharyngeal Candidiasis

• Moderate to severe disease: 100-200 mg IV daily for 7-14 days 1
• Note: Oral therapy is preferred when tolerable; IV reserved for patients unable to swallow 1, 4

Cryptococcal Meningitis

• Acute treatment: 400 mg (6 mg/kg) IV daily, OR 800 mg (12 mg/kg) IV daily based on severity 1, 3
• Duration: 10-12 weeks after CSF becomes culture-negative 3
• Consolidation phase: 400-800 mg daily for 8 weeks 5

Urinary Tract Candidiasis

• Dose: 200-400 mg (3-6 mg/kg) IV daily for 2 weeks 2
• Advantage: Fluconazole achieves urinary concentrations 10-20 times higher than serum levels 4, 6

Renal Dose Adjustments

Creatinine Clearance >50 mL/min

• No adjustment needed: Use standard dosing based on indication 2, 5, 3

Creatinine Clearance ≤50 mL/min

• Day 1: Administer full loading dose (400-800 mg depending on indication) 2, 5, 3
• Day 2 onward: Reduce maintenance dose to 50% of standard dose 2, 5, 3
• Example: If standard dose is 400 mg daily, give 200 mg daily 5

Hemodialysis Patients

• Loading dose: 800 mg (12 mg/kg) on day 1 2
• Maintenance: 400 mg (or 100% of recommended dose) after each hemodialysis session 2, 5, 3
• Frequency: Typically 3 times weekly for standard intermittent hemodialysis 2
• Non-dialysis days: Give reduced dose according to creatinine clearance 3
• Rationale: Approximately 50% of fluconazole is removed during a 3-hour hemodialysis session 5

Pediatric Dosing

Children ≥3 Months

• Loading dose: 12 mg/kg IV on day 1 (maximum 800 mg) 3
• Maintenance: 6-12 mg/kg IV once daily (maximum 400 mg) 3
• Candidemia duration: Minimum 3 weeks and at least 2 weeks after symptom resolution 3

Neonates and Infants <3 Months

Gestational age ≥30 weeks:

• Loading dose: 25 mg/kg IV on day 1 3
• Maintenance: 12 mg/kg IV once daily 3

Gestational age <30 weeks:

• Loading dose: 25 mg/kg IV on day 1 3
• Maintenance: 9 mg/kg IV once daily 3

Pediatric Patients on ECMO

• Age ≥3 months: 35 mg/kg loading dose (max 800 mg), then 12 mg/kg daily (max 400 mg) 3
• Age <3 months, GA ≥30 weeks: 35 mg/kg loading dose, then 12 mg/kg daily 3
• Age <3 months, GA <30 weeks: 35 mg/kg loading dose, then 9 mg/kg daily 3

Preparation and Infusion

Infusion Rate

• Maximum rate: 200 mg/hour as continuous infusion 3
• Example: 400 mg dose should infuse over minimum 2 hours 3

Preparation

• Ready-to-use: Fluconazole injection comes premixed in glass or plastic containers 3
• Inspection: Check for particulate matter, cloudiness, or precipitation before use 3
• Do not add supplementary medications to the fluconazole solution 3

Administration Precautions

• Never use plastic containers in series connections: This can cause air embolism 3
• Check inner bag for leaks by squeezing firmly before use 3
• Remove overwrap only when ready to use to maintain sterility 3

Criteria for Switching to Oral Therapy

When to Switch

Switch from IV to oral fluconazole as soon as the patient can tolerate oral intake, even mid-treatment. 1, 4

Therapeutic Equivalence

• Bioavailability: Oral fluconazole achieves ≈90% bioavailability of IV dosing 4
• Clinical equivalence: Both routes provide identical therapeutic outcomes for invasive candidiasis, candidemia, and CNS infections 4
• Tissue penetration: Both formulations achieve excellent tissue levels, including 50% of serum levels in CSF 4

Practical Algorithm

1. Assess oral intake capability daily 4
2. If patient can swallow and has no severe GI symptoms: Switch to oral 4
3. If patient cannot swallow or has severe nausea/vomiting: Continue IV 4
4. Use same dose: 400 mg IV = 400 mg oral 4

Benefits of Early Switch

• Reduced costs compared to continued IV therapy 4
• Lower risk of catheter-related infections 4
• Equal efficacy for serious infections including candidemia 4

Common Pitfalls and Caveats

Dosing Errors

• Do not reduce dose at CrCl 60 mL/min: The threshold for dose reduction is CrCl ≤50 mL/min, not 60 2, 5
• Always give full loading dose: Even in renal impairment, day 1 loading dose should be full strength 2, 5, 3
• Do not skip loading dose: Essential to achieve therapeutic concentrations quickly 5

Route Selection Mistakes

• Do not default to IV for hospitalized patients: Oral therapy is equally effective once oral intake is possible 4
• Do not continue IV unnecessarily: Switch to oral as soon as feasible to reduce complications 4

Species-Specific Considerations

• Candida krusei is intrinsically resistant to fluconazole: Select an alternative antifungal (amphotericin B or echinocandin) 1, 2
• Candida glabrata may require higher doses or alternative therapy 1

Drug Interactions

• Monitor closely: Fluconazole inhibits CYP3A4 and CYP2C9 5, 7
• High-risk medications: Cyclosporine, phenytoin, oral hypoglycemics, warfarin, antiretroviral drugs 5, 7, 8
• Adjust concomitant medications regardless of renal dosing 5

Absorption Considerations

• Fluconazole absorption is NOT affected by:
  • Proton-pump inhibitors or H₂-blockers 4
  • Food intake 4, 9
  • Gastric pH 4
• This distinguishes fluconazole from other azoles like itraconazole 4

Monitoring Requirements

• Renal function: Monitor regularly during therapy; changes in CrCl may require dose adjustments 5
• Ophthalmologic exam: All candidemia patients need dilated retinal exam within first week (delay until neutrophil recovery in neutropenic patients) 1
• Blood cultures: Repeat to document clearance 2

Duration Considerations

• Half-life: Approximately 30 hours in normal renal function, allowing once-daily dosing 5, 7
• Tissue persistence: Drug remains detectable in tissues for up to 6 months after discontinuation 5
• Minimum treatment: Most invasive infections require at least 14 days after documented clearance 1, 2