Fluconazole
Fluconazole is a systemic **triazole antifungal** agent. Unlike older first-generation azoles (such as ketoconazole), it is highly hydrophilic, allowing for excellent penetration into the **central nervous system (CSF)**, **eyes**, and **urinary tract**. > **Clinical Pearl:** Fluconazole does not require an acidic gastric environment for absorption, making its oral bioavailability highly reliable even in patients receiving antacid therapy. Furthermore, it has a significantly lower affinity for mammalian cytochrome P450 enzymes compared to ketoconazole, meaning it has minimal impact on mammalian steroid hormone synthesis and generally fewer side effects.
Mechanism: Fluconazole acts by inhibiting the fungal cytochrome P450-dependent enzyme **lanosterol 14-ฮฑ-demethylase**. Lanosterol โ (blocked by fluconazole) โ **Ergosterol** This depletion of ergosterol disrupts the synthesis of the fungal cell membrane, increasing its permeability and causing leakage of essential cellular contents. It also impairs the uptake of purine and pyrimidine precursors. Fluconazole is primarily **fungistatic**.
Dosing by species
- Nasal or dermal cryptococcosis ยท 5-10 mg/kg PO q12-24h, or 10 mg/kg PO q24h ยท PO ยท q12-24h ยท For most infections, 50 mg/cat PO once daily achieves adequate therapeutic levels
- CNS, intraocular, or multisystemic cryptococcosis ยท 50-100 mg/cat PO or IV q12h ยท PO/IV ยท q12h ยท Often treat neurologic ocular cryptococcosis for at least 12 weeks or 2 weeks after CSF exam shows resolution
- CNS, intraocular or multisystemic mycoses ยท 50 mg/cat PO once daily (q24h) ยท PO ยท q24h
- Cryptococcosis ยท 50 mg (total dose) PO twice daily ยท PO ยท q12h ยท 1 month beyond resolution of clinical signs
- Cryptococcosis ยท 50 mg (total dose) PO twice daily ยท PO ยท q12h ยท At least 2 months beyond resolution of clinical signs
- C. immitis infection or Candida bacteremia ยท Loading dose of 14 mg/kg followed by 5 mg/kg PO once daily ยท PO ยท q24h
- Fungal keratitis ยท 1 mg/kg PO q24h ยท PO ยท q24h ยท Anecdotal reports of successful treatment
- Candidiasis (cockatoos, parrots) ยท 20 mg/kg PO q24-48h or 10 mg/kg PO q24h ยท PO ยท q24-48h ยท Likely effective for C. albicans. C. galabrata and C. papasilosis may have higher MICs.
- Candidiasis (cockatiels) ยท 10 mg/kg fluconazole PO suspension and 100 mg/mL fluconazole treated drinking water ยท PO ยท Maintained plasma levels above the MIC for most strains of Candida albicans
Routes of administration
Contraindications
- Hypersensitivity to fluconazole or other azole antifungals
- Budgerigars (reportedly toxic)
- Pregnant animals
- Lactating animals
Adverse effects
- Inappetence
- Vomiting
- Diarrhea
- Hepatotoxicity (rare)
- Headache (humans)
- Increased liver enzymes (humans)
- Exfoliative skin disorders (humans)
- Thrombocytopenia (humans)
- Nausea
- Diarrhoea
- Hepatotoxicity
Drug interactions
- Amphotericin B ยท May be antagonistic against Aspergillus or Candida; clinical importance unclear
- Buspirone ยท Plasma concentrations of buspirone may be elevated
- Cisapride ยท May increase cisapride levels and the possibility for toxicity
- Corticosteroids ยท May inhibit the metabolism of corticosteroids; potential for increased adverse effects
- Cyclophosphamide ยท May inhibit the metabolism of cyclophosphamide and its metabolites; potential for increased toxicity
- Cyclosporine ยท Increases cyclosporine levels; dosage of cyclosporine may need to be decreased by 29%-51%
- Diuretics, Thiazides ยท Increased fluconazole concentrations
- Fentanyl/Alfentanil ยท May increase fentanyl levels
- Midazolam ยท Increased midazolam levels and effects
- NSAIDs ยท May increase NSAID plasma levels; increased risk for adverse effects
- Quinidine ยท Increased risk for cardiotoxicity
- Rifampin ยท May decrease fluconazole efficacy; fluconazole may increase rifampin levels
- Theophylline/Aminophylline ยท Increased theophylline concentrations
Monitoring
- Clinical efficacy
- Liver function tests (occasional, with long-term therapy)
- Liver enzyme panel (ALT, AST, ALP, Bilirubin) prior to and during prolonged therapy
- Renal function (BUN, Creatinine)
- Resolution of clinical signs of fungal infection
- Therapeutic drug monitoring for concurrent medications like ciclosporin or theophylline
Overdose
There is limited information on acute toxicity in domestic animals. In rodents, massive overdoses (1-2 g/kg) caused respiratory depression, salivation, lacrimation, urinary incontinence, and cyanosis, leading to death within several days. **Treatment:** If a massive overdose occurs, consider gut emptying (emesis or gastric lavage) if recent, and provide supportive therapy as required. Fluconazole may be removed by hemodialysis or peritoneal dialysis.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.