Neonatal Drug Therapy Manual

Fluconazole

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Updated August 23, 2023 - 3:00pm

Alternate Name(s): 
Diflucan
Classification: 
Antifungal Agent
Original Date: 
August 2003
Revised Date: 
June 2023
Indications: 
  • Treatment of invasive candidal infections, esophageal candidiasis, UTI and pneumonia
  • Treatment of thrush
  • Prophylaxis for the prevention of invasive candidiasis
Administration: 
  • IV intermittent infusion: over 1 - 2 hours (for doses > 6 mg/kg, administer IV over 2 hours)
  • PO
Dosage: 

Treatment - invasive candidiasis

GA 26-29 weeks:

  • PNA 0-7 days: 12 mg/kg IV on day 1, followed by 12 mg/kg IV Q48h starting on day 2
  • PNA >7 days: 12 mg/kg IV on day 1, followed by 12 mg/kg IV q24h starting on day 2

GA 30-40 weeks: 12 mg/kg IV q24h

AAP guidelines recommend a loading dose of 25mg/kg initially. This could be used in selected circumstances such as patients with severe illness, suspected CNS infections or patients on ECMO (considering hepatic and renal status as well as other potential medication interactions).

 

Treatment - oropharyngeal* candidiasis (thrush)

  • 6mg/kg PO/IV q 24 hours

     *maintenance doses up to 12 mg/kg may be required for treating esophageal candidiasis

 

  • Prophylaxis for the prevention of invasive candidiasis

** Based upon the current available literature, our approach is not to start antifungal prophylaxis for all premature infants because of the concern of promoting resistant Candida species within the NICU.

** Prophylactic fluconazole may be considered in infants with a high risk of invasive fungal infections such as extremely low birth weight infants (birth weight below 1000 g) with additional risk factors such as prolonged treatment with systemic broad-spectrum antibiotics.

  •  6 mg/kg/dose IV twice a week until intravenous access no longer is required for care

Dosage adjustment required in renal impairment.  Refer to available references or clinical pharmacist for dosage adjustment.  Dosage adjustment may also be required if liver enzymes become elevated.

Side Effects: 
  • CVS: QT interval prolongation reported
  • GI: nausea, vomiting, diarrhea, abdominal pain
  • Hematologic: eosinophilia, leukopenia, thrombocytopenia (rare)
  • Hepatic: elevated AST, ALT, or ALP; hepatitis; cholestasis
Parameters to Monitor: 
  • Periodic liver function test
  • Renal function
Reconstitution and Stability: 
  • Fluconazole 2 mg/mL:
    • Available as Fluconazole 2 mg/mL solution: No reconstitution necessary
    • Final concentration: 2 mg/mL
Compatibility: 

- Solutions Compatible: D5W or 0.9 % NaCl

- Y-site Compatible: acyclovir, dopamine, dobutamine, fentanyl, gentamicin, heparin, midazolam, morphine, tobramycin, TPN (amino acids- dextrose), vancomycin

Incompatible: ampicillin, amphotericin B, calcium gluconate 100 mg/mL (undiluted), cefotaxime, ceftazidime, cefuroxime, clindamycin, erythromycin, furosemide, piperacillin, SMOF

References: 

-Taketomo CK, Hodding JH, Kraus DM. Pediatric & Neonatal Dosage Handbook 22nd Edition. Hudson: Lexi-Comp Inc.; 2015

-Trissel LA. Handbook on Injectable Drugs. 16th Editions. Bethesda: American Society of Health-System Pharmacists; 2011

-King JC. King Guide to Parenteral Admixtures. Internet Edition.

- Piper et al.  Fluconazole Loading Dose Pharmacokinetics and Safety in Infants.  Pediatr Infect Dis J 2011; 30: 375-378

- American Academy of Pediatrics. In Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds.  Red Book: 2012. Report of the Committee on Infectious Diseases. Elk. Grove Village, IL: American Academy of Pediatrics; 2012: 268-69

- Wade et al. Population Pharmacokinetics of Fluconazole in Young Infants. Antimicrob. Agents Chemother. 2008; 52; 4043 - 49

- Wade et al.  Fluconazole Dosing for the Prevention of treatment of Invasive Candidiasis in Young Infants.  Pediatr Infect Dis J 2009; 28: 717-23

- Pacifici. Clinical Pharmacology of Fluconazole in Neonates: Effects and Pharmacokinetics. Volume 4, Issue 3 - Serial Number 3. March 2016. Pages 1475-1489.

-Leroux S, Jacqz-Aigrain E, Elie V, Legrand F, Barin-Le Guellec C, Aurich B, Biran V, Dusang B, Goudjil S, Coopman S, Garcia Sanchez R, Zhao W, Manzoni P; FP7 TINN (Treat Infections in NeoNates) consortium. Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial. Br J Clin Pharmacol. 2018 Sep;84(9):1989-1999.

- Hornik CD, Bondi DS, Greene NM, Cober MP, John B. Review of Fluconazole Treatment and Prophylaxis for Invasive Candidiasis in Neonates. J Pediatr Pharmacol Ther. 2021;26(2):115-122. doi: 10.5863/1551-6776-26.2.115.

- Murakoso K, Minagawa R, Echizen H. Developmental changes of fluconazole clearance in neonates and infants in relation to ontogeny of glomerular filtration rate: literature review and data analysis. J Pharm Health Care Sci. 2018 Mar 20;4:5.

 

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