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Dose and administration
Intravenous and oral
|<7 days||q 72hrs|
|7-14 days||q 48hrs|
|>14 days||q 24hrs|
|<14 days||q 72hrs|
|14 - 28 days||q 48hrs|
|>28 days||q 24hrs|
Administer IV dose over 30-120 minutes1
Treatment of suspected systemic fungal infection and extensive cutaneous and confirmed Candidiasis once sensitivities confirmed.
- 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 death.
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).
|Amphotericin||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.|
|Caffeine||Possible increase in caffeine levels.|
|Cisapride||Increases risk of arrhythmias|
|Erythromycin||Prolongation of QT interval possible|
|Fentanyl||Possible decrease in fentanyl elimination|
|Chlorothiazide||Given orally with oral fluconazole may increase fluconazole levels|
|Midazolam||Increases half-life of midazolam (more likely with higher doses long term)|
|Theophylline||Raises theophylline levels|
|Phenytoin||Raises phenytoin levels - (measure serum levels and reduce phenytoin dose if necessary); possible decrease in fluconazole levels; increase in LFTs|
|Rifampicin||Decreases fluconazole levels, possible increase in LFTs|
|Zidovudine||Increase in zidovudine levels|
Possible adverse effects
- Hepatic toxicity. Discontinue if signs and symptoms of liver disease develop.
- Prolongation of QT interval.
- Rash - monitor carefully.
- Rarely: leukopenia, thrombocytopenia, toxic epidermal necrolysis, Stevens-Johnson syndrome.
- Monitor: Renal
& hepatic function Consider reducing dose if there is renal
Mild to moderate renal impairment: give 50% normal dose
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 4
- 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.
Management of IV Fluconazole administration
- Injection fluconazole 2mg/ml . pH:4 - 8. Osmolality 315 mOsm/L
- Oral: dry powder for reconstitution to a solution containing fluconazole 50mg/5ml Oral
Charted on the prescription chart in mg/dose
- Administer undiluted, through a PALL 0.2 micron filter, over 60 minutes.
- Compatible with glucose 5%, glucose 10%, and sodium chloride 0.9%.
- Incompatible with frusemide, calcium gluconate. Do NOT mix with other medications.
Oral doses can be given with food.
- Monitor ECG, renal function, LFTs, FBC.
- Monitor for diarrhoea and feeding intolerance
- Monitor for other adverse effects eg. rash
- Injection vials: room temperature, below 30°C.
- Reconstituted oral solution: between 5-30°C (preferably in fridge). Note expiry date on label.
- Phelps SJ, Hak EB, Crill CM, editors. Teddy bear book: Pediatric injectable drugs. 8th ed. Bethesda, MD: American Society of Heath-System Pharmacists; 2007.
- Hey, E, editor. Neonatal formulary. 5th ed. Oxford: Blackwell Publishing; 2007
- Young TE, Mangum B, editors. Neofax: A manual of drugs used in neonatal care. 18th ed. Raleigh, North Carolina, USA: Acorn Publishing; 2005.
- Fluconazole dosing for the prevention or treatment of invasive candidiasis in young infants. Wade KC, Benjamin DK Jr, Kaufman DA, Ward RM, Smith PB, Jayaraman B, Adamson PC, Gastonguay MR, Barrett JS.Pediatr Infect Dis J. 2009 Aug;28(8):717-23
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- Date last published: 30 April 2014
- Document type: Drug Dosage Guideline
- Services responsible: ADHB Pharmacy, Neonatology
- Editor: Sarah Bellhouse
- Review frequency: 2 years