FLUCONAZOLE

Disclaimer to the On-line Edition
This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.

FLUCONAZOLE

Indication

  • fluconAZOLE is a triazole antifungal agent that may be used for prophylaxis against or treatment of mucocutaneous, systemic and cerebrospinal Candida infections, most specifically C. albicans.

Pharmacology

  • fluconAZOLE is a broad-spectrum, antifungal agent that has excellent activity against many Candida species. However, C. krusei and C. glabrata are resistant.
  • fluconAZOLE is fungistatic; it works by decreasing ergosterol synthesis and inhibiting formation of the fungal cell membrane
  • fluconAZOLE has excellent penetration into the CSF and joint spaces, and is excreted unchanged in the urine
  • fluconAZOLE is available in both IV and oral formulations; oral fluconAZOLE is rapidly absorbed by the gastrointestinal tract, with an estimated bioavailability of over 90%

Side Effects

  • generally well tolerated; more favourable side-effect profile than amphotericin B
  • may cause vomiting, diarrhea, rash, elevations in liver enzymes
  • rare adverse effects: angioedema, hypokalemia, leucopenia, neutropenia, thrombocytopenia

Precautions

  • periodic monitoring of liver enzymes, renal function tests, potassium, CBC and differential is recommended
  • use with caution in patients with liver impairment.
  • dose adjustment required in patients with renal impairment
    • moderate impairment – reduce dose by 50%
    • severe impairment – reduce dose by 75%
  • interferes with metabolism of PHENObarbital, phenytoin, caffeine and midazolam
  • may cause QTc prolongation and torsades de pointes; use caution in patients with concomitant medications or conditions which are arrhythmogenic
  • avoid using in patients receiving erythromycin

Dose

Treatment of Systemic Candidiasis, including meningitis:

  • loading dose
    25 mg/kg/dose IV/oral may be used in select cases
  • maintenance dose
    12 mg/kg/dose IV/oral once daily starting 24 hours after loading dose

Treatment of Thrush:

  • loading dose
    6 mg/kg/dose oral on day 1
  • maintenance dose
    3 mg/kg/dose oral daily

Prophylaxis: (Consider for neonates with a birth weight less than 1000 g)

Gestational Age Postnatal Age Dose
Less than 30 weeks Less than 7 days 3 mg/kg/dose IV/oral Q72h
Greater than 7 days 3 mg/kg/dose IV/oral daily
30 to 40 weeks All 6 mg/kg/dose IV/oral Q48h
  • Duration of prophylaxis should be guided by the presence of risk factors

Administration:

Loading Dose

  • administer by slow IV infusion over at least 2 hours

Maintenance Dose

  • administer by slow IV infusion over 2 hours

**NOT COMPATIBLE WITH SMOF LIPIDS**

Supplied

  • syringe (2 mg/mL) prepared by pharmacy for immediate use – RN to notify pharmacy to request dose 30 minutes to 1 hour prior to administration time
  • 10 mg/mL oral suspension

References

  1. Lexicomp Online, Fluconazole (Pediatric and Neonatal Lexi-Drugs) Lexi-Drugs Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2018. Accessed January 29, 2019
  2. Lexicomp Online, Fluconazole (The Hospital for Sick Children Electronic Formulary) Lexi-Drugs Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2018. Accessed January 29, 2019
  3. Turner, K, et al.  Fluconazole pharmacokinetics and safety in premature infants. Curr Med Chem, (2012)19(27), 4617-4620.
  4.  Pacifici M,G. Clinical Pharmacology of Fluconazole in Neonates: Effects and Pharmacokinetics. Int J Pediatr 2016; 4(3): 1475-89.
  5. Cleminson J, Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database of Systematic Reviews 2015, Issue 10. Art. No.: CD003850. DOI: 10.1002/14651858.CD003850.pub5.

Updated: February 2019

 

 

 

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