Fluconazole

Antifungal Triazole antifungal

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 5-10 mg/kg q12h or q24h Duration: Variable; often 2-6 months for systemic mycoses; treat until clinical resolution and negative antigen tests
Notes: For CNS infections, use higher end of dose range. For dermatophytosis, lower doses may be used.
Cat PO 5-10 mg/kg q12h or q24h Duration: Variable; often 2-6 months for cryptococcosis; treat until clinical resolution and negative antigen tests
Notes: Cats are sensitive to overdose; monitor for hepatotoxicity. For CNS infections, use higher end.
Horse PO 5-10 mg/kg q24h Duration: Variable; weeks to months depending on infection
Notes: For fungal keratitis, may also use topical 1% solution. Monitor liver enzymes.
Cattle PO 5-10 mg/kg q24h Duration: Variable; often 2-4 weeks
Notes: Extra-label use; observe withdrawal times. For mastitis, may be used systemically.
Small Ruminants (sheep/goats) PO 5-10 mg/kg q24h Duration: Variable; 2-4 weeks
Notes: Extra-label use; monitor for adverse effects.
Rabbit PO 10-20 mg/kg q24h Duration: Variable; 2-4 weeks
Notes: Limited data; use cautiously.
Birds (psittacines) PO 10-20 mg/kg q12h or q24h Duration: Variable; often 2-6 weeks
Notes: For aspergillosis, may be used as adjunct to itraconazole or amphotericin B.
Reptiles PO 10-20 mg/kg q24-48h Duration: Variable; 2-4 weeks
Notes: Limited data; adjust based on species and temperature.

Clinical Indications & Species Uses

General Indications
  • Treatment of susceptible fungal infections, especially those caused by Candida, Cryptococcus, and dimorphic fungi
  • Off-label use in many species
Dog (Canine)
  • Treatment of systemic mycoses (blastomycosis, histoplasmosis, coccidioidomycosis, cryptococcosis)
  • Candidiasis (oral, urinary, systemic)
  • Dermatophytosis (as adjunct or alternative to topical therapy)
  • Fungal meningitis (due to good CNS penetration)
  • Ocular fungal infections (e.g., keratomycosis)
Cat (Feline)
  • Cryptococcosis (especially nasal and CNS)
  • Systemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis)
  • Candidiasis
  • Dermatophytosis (especially in severe or refractory cases)
  • Fungal rhinitis
Horse (Equine)
  • Systemic mycoses (e.g., histoplasmosis, cryptococcosis)
  • Fungal keratitis (topical and systemic)
  • Candidiasis (especially in foals)
  • Fungal pneumonia (e.g., Aspergillus, but less effective)
Cattle (Bovine)
  • Systemic mycoses (e.g., mycotic mastitis, fungal pneumonia)
  • Candidiasis (e.g., oral thrush in calves)
  • Dermatophytosis (ringworm) - though topical therapy is preferred
Small Ruminants (Sheep / Goat)
  • Systemic mycoses (e.g., cryptococcosis, histoplasmosis)
  • Candidiasis
  • Dermatophytosis (off-label use)
Rabbit & Small Mammals
  • Systemic mycoses (e.g., cryptococcosis, candidiasis)
  • Dermatophytosis (off-label use)
Avian & Poultry
  • Candidiasis (e.g., crop mycosis in psittacines)
  • Systemic mycoses (e.g., aspergillosis - though less effective, often used as adjunct)
  • Cryptococcosis
Exotic & Other Species
  • Reptiles: systemic mycoses (e.g., fungal dermatitis, pneumonia)
  • Small mammals (ferrets, guinea pigs): candidiasis, systemic mycoses

Pharmacology & Mechanism of Action

Drug Class: Antifungal | Pharmacological Group: Triazole antifungal

Mechanism of Action: Fluconazole is a synthetic triazole antifungal agent that selectively inhibits fungal cytochrome P450-dependent enzyme lanosterol 14-α-demethylase, which is essential for the conversion of lanosterol to ergosterol. Ergosterol is a critical component of the fungal cell membrane. Inhibition of its synthesis leads to increased membrane permeability, leakage of cellular contents, and ultimately fungal cell death. Fluconazole is primarily fungistatic, but may be fungicidal at high concentrations against some organisms. It is selective for fungal CYP450 enzymes, with minimal affinity for mammalian enzymes, which contributes to its safety profile.

Pharmacodynamics: Fluconazole exhibits broad-spectrum antifungal activity against many pathogenic fungi, including Candida spp., Cryptococcus neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis, and some dermatophytes. It is less effective against Aspergillus spp. and some molds. The drug is generally fungistatic, requiring host immune response for fungal eradication. In veterinary medicine, it is commonly used for systemic mycoses and candidiasis. Its efficacy is dose-dependent, and resistance can develop, particularly in Candida species with prolonged use.

⚡ Pharmacokinetics Summary

Absorption: Fluconazole is well absorbed after oral administration in most species, with bioavailability exceeding 90% in dogs and cats. Absorption is not significantly affected by food, gastric pH, or concurrent administration of antacids. Peak plasma concentrations are achieved within 1-2 hours in dogs and cats, and 0.5-1.5 hours in horses. In birds, absorption is variable but generally good.
Distribution: Fluconazole is widely distributed throughout the body, including into cerebrospinal fluid (CSF), where concentrations reach 50-90% of plasma levels. It also penetrates well into ocular tissues, skin, and vaginal tissues. The volume of distribution is approximately 0.7 L/kg in dogs and 0.6 L/kg in cats. Protein binding is low (11-12% in humans, similar in animals).
Metabolism: Fluconazole is minimally metabolized in the liver. It is a weak inhibitor of CYP450 enzymes, but its own metabolism is limited. In dogs, a small portion is metabolized to inactive metabolites, but the majority is excreted unchanged. In cats, metabolism is also minimal.
Excretion: Fluconazole is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. Renal clearance accounts for about 70-80% of total clearance. In animals with renal impairment, the half-life is prolonged, and dose adjustments are necessary. Fecal excretion is minimal.
Half-Life: Dog: approximately 25-30 hours; Cat: approximately 25-30 hours; Horse: approximately 20-30 hours; Cattle: approximately 20-30 hours; Birds: variable, often 10-20 hours.
Bioavailability: Oral bioavailability is high: >90% in dogs and cats, ~100% in horses, and variable in birds (often 60-100%).
Protein Binding: Low (approximately 11-12% in dogs and cats).

Available Formulations & Strengths

Oral Tablet 50 mg, 100 mg, 150 mg, 200 mg (PO)
Oral Suspension 10 mg/mL, 40 mg/mL (PO)
Injectable Solution (IV) 2 mg/mL in 0.9% NaCl (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to fluconazole or other azole antifungals
  • Concurrent use with drugs that are contraindicated with fluconazole (e.g., cisapride, terfenadine, astemizole) due to risk of QT prolongation
  • Severe hepatic impairment (use with caution)
  • Pregnancy (especially first trimester) unless benefits outweigh risks; teratogenic in animals at high doses
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic disease; monitor liver enzymes periodically.
  • Use with caution in animals with renal impairment; dose adjustment may be necessary.
  • Cats are particularly sensitive to fluconazole; overdose can cause severe neurological signs and hepatotoxicity.
  • May cause QT prolongation; use with caution in animals with cardiac disease or those receiving other QT-prolonging drugs.
  • Not recommended for use in pregnant animals unless clearly necessary; may cause fetal abnormalities.
  • In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
  • May interact with many drugs; review medication history.
  • In birds, use with caution; monitor for regurgitation and liver toxicity.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Elevated liver enzymes (ALT, AST)
  • Lethargy

Serious / Severe:

  • Hepatotoxicity (especially in cats)
  • Severe skin reactions (rare)
  • QT prolongation and cardiac arrhythmias
  • Neurological signs (seizures, ataxia) in overdose

Rare:

  • Blood dyscrasias (thrombocytopenia, leukopenia)
  • Anaphylaxis
  • Stevens-Johnson syndrome

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Cisapride Increased risk of QT prolongation and ventricular arrhythmias; contraindicated. High
Terfenadine, Astemizole Increased risk of QT prolongation; contraindicated. High
Warfarin and other anticoagulants Increased anticoagulant effect; monitor coagulation parameters. Moderate
Phenytoin Increased phenytoin levels; monitor for toxicity. Moderate
Rifampin Decreased fluconazole levels; may require dose adjustment. Moderate
Sulfonylureas (e.g., glipizide) Increased risk of hypoglycemia; monitor blood glucose. Moderate
Cyclosporine Increased cyclosporine levels; monitor renal function and drug levels. Moderate
Benzodiazepines (e.g., midazolam) Increased benzodiazepine levels; potential for enhanced sedation. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Anorexia
  • Lethargy
  • Ataxia
  • Tremors
  • Seizures
  • Hepatotoxicity (elevated liver enzymes, jaundice)
  • In cats: severe neurological signs, depression, and hepatic necrosis

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce vomiting if recent ingestion (within 1-2 hours) in dogs and cats. Administer activated charcoal to reduce absorption. Provide intravenous fluids to maintain hydration and promote renal excretion. Monitor liver enzymes and renal function. In severe cases, consider hemodialysis (fluconazole is dialyzable). Seizures may be managed with anticonvulsants (e.g., diazepam).

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not established for fluconazole in food animals in many countries. The values provided are based on reasonable estimates and should be used as a guide. Extra-label use requires veterinary oversight and extended withdrawal periods may be necessary. Consult regulatory authorities for specific guidance.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature, 20-25°C (68-77°F).

Handling & Special Conditions: Protect from moisture. Keep container tightly closed. Oral suspension: store at room temperature, do not freeze. Injectable solution: store at room temperature, protect from freezing.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. However, it is widely used in veterinary medicine as an extra-label drug.

Extra-Label (Off-Label) Use: In the US, fluconazole is not FDA-approved for veterinary use, but it is commonly used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA). Extra-label use is permitted in animals under the supervision of a veterinarian, provided that a valid veterinarian-client-patient relationship exists and appropriate withdrawal times are observed for food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Fluconazole is a valuable antifungal agent in veterinary medicine due to its excellent oral bioavailability, wide distribution (including CNS), and favorable safety profile compared to other azoles. It is particularly useful for long-term therapy of systemic mycoses such as cryptococcosis, blastomycosis, and histoplasmosis. However, it is less effective against Aspergillus and some molds, where itraconazole or amphotericin B may be preferred. In cats, careful dosing is essential to avoid toxicity; monitoring liver enzymes is recommended. In food animals, extra-label use requires attention to withdrawal times. Fluconazole is generally well-tolerated, but drug interactions should be considered, especially with drugs that prolong QT interval. For optimal outcomes, treatment should be guided by culture and susceptibility testing when possible, and continued until clinical resolution and negative antigen tests (e.g., for Cryptococcus).

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)