NICU and Dept. of Pharmacy
Dose and Administration
Intravenous & oral
Administer IV dose over 30-120 minutes1
- Treatment of suspected systemic
fungal infection and extensive cutaneous and confirmed Candidiasis once
- Co-administration of other drugs which might prolong the QT interval.
- Hypersensitivity to fluconazole or related azole compounds.
- Administer with caution in patients with liver dysfunction. Discontinue if
signs and symptoms of liver disease develop.
- Impaired renal or hepatic function. Dose reduction recommended in renal
impairment – see "Special Considerations".
Fluconazole is a highly selective
inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation, thus
inhibiting ergosterol synthesis. Ergosterol is an essential component of the
fungal cell membrane, and instability of the cell membrane results in cell
It is water-soluble and is well
absorbed from the gastrointestinal tract, although it is not generally used via
this route in neonates. Oral absorption is unaffected by food intake. It has
good CSF penetration and is excreted largely unchanged in urine, therefore dose
adjustments are necessary in the presence of impaired renal function. Neonates
have a greater volume of distribution and decreased elimination rates compared
to older children and adults. The plasma half life in neonates is approximately
70 hours (30 hours in adults). In preterm infants fluconazole was found to have
a plasma half life=73 hours (at birth), 53 hours (6 days of age), and 46 hours
(at 12 days of age).
|| Currently not
established if the combination is beneficial or of reduced benefit in
terms of antifungal reponse. There is theoretical antagonism seen in
vitro but not in vivo.
increase in caffeine levels.
|| Increases risk
|| Prolongation of QT interval possible
|| Possible decrease in fentanyl
|| Given orally
with oral fluconazole may increase fluconazole levels
half-life of midazolam (more likely with higher doses long term)
phenytoin levels – (measure serum levels and reduce phenytoin dose if
necessary); possible decrease in fluconazole levels; increase in LFTs
fluconazole levels, possible increase in LFTs
Possible Adverse Effects
- Hepatic toxicity. Discontinue if signs and symptoms of liver disease
- Prolongation of QT interval.
- Rash – monitor carefully.
- Rarely: leukopenia, thrombocytopenia, toxic epidermal necrolysis,
- Monitor: Renal & hepatic function Consider reducing dose if there is renal impairment1:
- Mild to moderate renal impairment: give 50%
- Moderate to severe renal impairment: give 50%
of normal dose and extend dosing interval.
- Do NOT give by IM or direct IV
bolus injection. Continuous infusion is not recommended
- Systemic Candidiasis is rare without evidence of superficial infection or colonisation.
- Not effective against some Candida species (i.e. C.krusei, C.glabrata)
- Amphotericin is still the drug of choice for proven Candida infection
until sensitivity to Fluconazole is confirmed. However, Fluconazole therapy
for established infection can be considered in consultation with the
Infectious Diseases service.