- Fluconazole is an antifungal agent indicated for the treatment of susceptible fungal organisms
- fluconazole is a broad-spectrum, antifungal agent that has excellent activity against many Candida species. However, resistance to C. kruseii, Torulopsis glabrata has been reported.
- fluconazole is fungistatic; it works by inhibiting formation of the cell membrane
- fluconazole has excellent penetration into the CSF (70-80%; higher in inflamed meninges) and joint space, and is excreted primarily in the urine
- available in both IV and oral formulations; oral fluconazole is rapidly absorbed by the gastrointestinal tract, with an estimated bioavailability of over 90%
- the combined use of a polyene (amphotericin B) and an azole (fluconazole) is controversial, since the former binds to ergosterol in the fungal cell membrane, and the latter inhibits the synthesis of ergosterol, thus causing possible antagonism
- may be useful in the treatment of Trichosporon beigelii, a fungus that has shown resistance to amphotericin B
- usually well tolerated; more favourable side-effect profile than amphotericin B
- may cause vomiting, diarrhea, rash, elevations in LFTs (mild and transient elevations in LFTs have been reported in a preterm infant)
- Baseline liver function tests, followed by bi-weekly liver function tests, is a practice that we have used in this unit. Regular monitoring of platelets is also recommended
Systemic Candidiasis, including meningitis:
Use in prophyalxis against fungal infection(1):
- Intravenous fluconazole has been used prophylactically, beginning within the first 5 days of birth, in preterm newborns (< 1,000 g) for 6 weeks. The dose used was 3 mg/kg q72h for the first 2 weeks, q48h for weeks 3 and 4, and q24h for weeks 5 and 6.
- administer by slow iv infusion over 2 hours; administer undiluted (2mg/mL solution)
- administer by slow iv infusion over 1 hour; administer undiluted (2mg/mL solution)
- **COMPATIBLE WITH LIPID/TPN**
- syringe (2 mg/mL) prepared by pharmacy
- 100 mL single-use vial of 2 mg/mL solution; administer undiluted, discard unused portion
- powder for oral suspension available (10 mg/mL after reconstitution; stable for 14 days); can be ordered in by pharmacy
- Taketomo CK, Hodding JH and Kraus DM: Pediatric Dosage Handbook, Lexi-Comp Inc., Cleveland, 1992.
- Young TE and Mangum OB: Neofax - A Manual of Drugs Used in Neonatal Care, Columbus, Ohio: Ross Laboratories, 1992.
- Driessen M, Ellis JB, Cooper PA et al. Fluconazole vs. Amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pedriatr Infect Dis J 1996;15:1107-12
- Fasano C, O'Keeffe J, Gibbs D. Fluconazole treatment of neonates with severe fungal infection not treatable with conventional agents. Eur J Clin Microbiol Infect Dis 1994;13:351-4
- Huang Y-C, Tzou-Yien L, Peng L. Outbreak of Candida albicans fungaemia in a neonatal intensive care unit. Scand J Infect Dis 1998;30:137-142
- Saxen H, Hoppu K, Pohjavuori M. Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life. Clin Pharmacol Therapeut 1993;54:269-77
- Wenzl TG, Schefels J, Hornchen H, Skopnik H. Pharmacokinetics of oral fluconazole in premature infants. Eur J Pediatr 1998;157:661-2
- Zenk KE. Neonatal medications & nutrition: a comprehensive guide. NICU Ink, Santa Rosa, CA 1999.
- Sugar AM. Use of amphotericin B with azole antifungal drugs - what are we doing? Antimicrob Agents Chemother 1995; 39: 1907-1912.
- Louie A, Banerjee P, Drusano GL, Shayegani M, Miller MH. Interaction between fluconazole and amphotericin B in mice with systemic infection due to fluconazole-susceptible or -resistant strains of Candida albicans. Antimicrob Agents Chemother 1999; 43: 2841-2847.
- Lewis RE, Lund BC, Klepser ME, Ernst EJ, Pfaller MA. Assessment of antifungal activities of fluconazole and amphotericin B administered alone and in combination against Candida albicans by using a dynamic in vitro mycotic infection model. Antimicrob Agents Chemother 1998; 42: 1382-1396.
- Yoss BS, Sautter RL, Brenker HJ. Trichosporon beigelii, a new neonatal pathogen. American Journal of Perinatology 1997: 14:113-117.
- Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M and Donowitz LG: Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med 2001;354:1660-6
Date of preparation: August 2001