Itraconazole

Antifungal Triazole Antifungal

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 5-10 mg/kg q24h Duration: For dermatophytosis: 2-4 weeks; for systemic mycoses: 4-6 months or longer
Notes: Administer with food. For blastomycosis, higher doses (10 mg/kg) may be needed. Monitor liver enzymes.
Cat PO 5-10 mg/kg q24h Duration: For dermatophytosis: 2-4 weeks; for cryptococcosis: 4-6 months or longer
Notes: Administer with food. Cats may require higher doses for CNS infections. Use oral solution for better absorption.
Horse PO 3-5 mg/kg q24h Duration: Variable, often weeks to months
Notes: Oral absorption is poor; consider compounded formulations or IV for severe infections.
Cattle PO 5-10 mg/kg q24h Duration: Variable
Notes: Not commonly used; extra-label use requires veterinary oversight. Observe withdrawal times.
Small Ruminants PO 5-10 mg/kg q24h Duration: Variable
Notes: Limited data; use with caution.
Rabbit PO 5-10 mg/kg q24h Duration: Variable
Notes: Limited data; use with caution.
Birds PO 5-10 mg/kg q12-24h Duration: Variable
Notes: For aspergillosis, higher doses may be needed. Use oral solution or compounded suspension.
Reptiles PO 5-10 mg/kg q24-48h Duration: Variable
Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications
  • Treatment of systemic and superficial fungal infections caused by susceptible organisms
Dog (Canine)
  • Dermatophytosis (ringworm)
  • Malassezia dermatitis
  • Blastomycosis
  • Histoplasmosis
  • Coccidioidomycosis (Valley fever)
  • Cryptococcosis
  • Sporotrichosis
  • Aspergillosis (nasal and systemic)
  • Candidiasis
  • Systemic mycoses
Cat (Feline)
  • Dermatophytosis (ringworm)
  • Cryptococcosis
  • Histoplasmosis
  • Sporotrichosis
  • Candidiasis
  • Systemic mycoses
Horse (Equine)
  • Dermatophytosis
  • Pythiosis (subcutaneous)
  • Aspergillosis (guttural pouch mycosis)
  • Candidiasis
Cattle (Bovine)
  • Dermatophytosis (ringworm)
  • Bovine mycotic abortion (rarely used)
  • Systemic mycoses (rarely used)
Small Ruminants (Sheep / Goat)
  • Dermatophytosis
  • Systemic mycoses (rarely used)
Rabbit & Small Mammals
  • Dermatophytosis
  • Systemic mycoses (rarely used)
Avian & Poultry
  • Aspergillosis (especially in raptors and waterfowl)
  • Candidiasis
  • Cryptococcosis
Exotic & Other Species
  • Reptiles: Dermatophytosis, systemic mycoses
  • Small mammals (ferrets, guinea pigs): Dermatophytosis, systemic mycoses

Pharmacology & Mechanism of Action

Drug Class: Antifungal | Pharmacological Group: Triazole Antifungal

Mechanism of Action: Itraconazole inhibits fungal cytochrome P450 14α-demethylase (CYP51), which is essential for the conversion of lanosterol to ergosterol, a critical component of the fungal cell membrane. This leads to accumulation of toxic methylated sterols and depletion of ergosterol, disrupting membrane integrity and function, ultimately causing fungal cell death. Itraconazole is primarily fungistatic but can be fungicidal at high concentrations against certain organisms.

Pharmacodynamics: Itraconazole exhibits broad-spectrum antifungal activity against dermatophytes (e.g., Microsporum, Trichophyton), yeasts (e.g., Candida, Malassezia), dimorphic fungi (e.g., Blastomyces, Histoplasma, Coccidioides), and some molds (e.g., Aspergillus, Sporothrix). It is more potent than ketoconazole and has a longer half-life. It also has anti-inflammatory and anti-angiogenic properties that may contribute to its therapeutic effects in some conditions.

⚡ Pharmacokinetics Summary

Absorption: Itraconazole is a weak base and requires an acidic environment for optimal absorption. Oral absorption is variable and enhanced when administered with food, particularly fatty meals. In dogs, absorption is improved when given with food; in cats, absorption is also improved with food. The oral solution (hydroxypropyl-β-cyclodextrin formulation) has better bioavailability than capsules.
Distribution: Itraconazole is highly lipophilic and extensively distributed to tissues, especially skin, nails, and adipose tissue. It achieves high concentrations in keratinous tissues and is slowly released. It penetrates the CNS poorly but can reach therapeutic levels in inflamed meninges. It crosses the placenta and is excreted in milk.
Metabolism: Itraconazole is extensively metabolized in the liver by cytochrome P450 enzymes (CYP3A4) into several metabolites, including hydroxy-itraconazole, which has antifungal activity. It undergoes significant first-pass metabolism, resulting in low systemic bioavailability of the parent drug.
Excretion: Itraconazole and its metabolites are excreted primarily in feces (about 40% as metabolites) and to a lesser extent in urine (about 35% as metabolites). Biliary excretion is a major route. Enterohepatic recirculation occurs.
Half-Life: Dogs: 24-48 hours; Cats: 24-48 hours; Horses: 8-10 hours (after IV); Humans: 20-60 hours.
Bioavailability: Oral bioavailability is variable and dose-dependent, ranging from 20-70% in dogs and cats. The oral solution has higher bioavailability (about 55% in dogs) compared to capsules (about 20-30%).
Protein Binding: Itraconazole is highly protein-bound (>99%) in plasma, primarily to albumin.

Available Formulations & Strengths

Capsule 100 mg (PO)
Oral Solution 10 mg/mL (PO)
Tablet (compounded) Various strengths (PO)
Injectable (compounded) Various strengths (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to itraconazole or other azole antifungals
  • Hepatic disease (severe)
  • Pregnancy (especially first trimester) unless benefits outweigh risks
  • Concurrent use with drugs that are strong CYP3A4 inhibitors or substrates with narrow therapeutic index (e.g., cisapride, dofetilide, ergot alkaloids, midazolam, triazolam, lovastatin, simvastatin)
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal impairment
  • Monitor liver enzymes (ALT, AST, ALP) and renal function periodically during therapy
  • May cause gastrointestinal upset; administer with food to reduce nausea
  • In cats, may cause anorexia and weight loss; monitor food intake
  • Use with caution in pregnant or lactating animals; potential teratogenic effects
  • May cause hypokalemia and hypertension in some animals
  • In horses, oral absorption is erratic; consider alternative routes or formulations
  • For food animals, observe withdrawal times; extra-label use requires veterinary oversight

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Elevated liver enzymes (ALT, AST, ALP)
  • Lethargy
  • Weight loss (especially in cats)

Serious / Severe:

  • Hepatotoxicity (hepatic necrosis, cholestasis)
  • Severe skin reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome)
  • Peripheral edema
  • Congestive heart failure (rare, but reported in humans; caution in animals with cardiac disease)
  • Hypokalemia
  • Adrenal suppression (with high doses)

Rare:

  • Thrombocytopenia
  • Leukopenia
  • Neurotoxicity (tremors, ataxia)
  • Photosensitivity
  • Alopecia

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Cisapride Increased risk of cardiac arrhythmias (QT prolongation, torsades de pointes) High
Dofetilide Increased risk of cardiac arrhythmias High
Ergot alkaloids (e.g., ergotamine) Increased risk of ergotism (vasospasm, ischemia) High
Midazolam, Triazolam Increased sedation and respiratory depression High
Lovastatin, Simvastatin Increased risk of rhabdomyolysis High
Digoxin Increased digoxin levels, risk of toxicity Moderate
Phenytoin Increased phenytoin levels, risk of toxicity Moderate
Warfarin Increased anticoagulant effect, risk of bleeding Moderate
Cyclosporine Increased cyclosporine levels, risk of nephrotoxicity Moderate
Antacids, H2 blockers, proton pump inhibitors Decreased itraconazole absorption due to reduced gastric acidity Moderate
Rifampin, Rifabutin Decreased itraconazole levels, reduced efficacy Moderate
Phenobarbital, Carbamazepine Decreased itraconazole levels, reduced efficacy Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe gastrointestinal distress (vomiting, diarrhea)
  • Hepatotoxicity (jaundice, elevated liver enzymes)
  • Lethargy
  • Hypokalemia
  • Cardiac arrhythmias (QT prolongation)

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Monitor liver function, electrolytes, and cardiac status. Provide intravenous fluids and supportive care. In severe cases, consider hemodialysis (though itraconazole is highly protein-bound, so efficacy is limited).

Food Animal Withdrawal Times

🥩 Meat: 28 days🥛 Milk: 7 days

Withdrawal times are not established for itraconazole in food animals. The values provided are conservative estimates based on pharmacokinetic data and are for guidance only. Extra-label use in food animals requires veterinary oversight and extended withdrawal periods may be necessary. Consult FARAD (Food Animal Residue Avoidance Databank) for current recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep container tightly closed. Do not freeze the oral solution.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. Veterinary use is extra-label.

Extra-Label (Off-Label) Use: Itraconazole is not FDA-approved for veterinary species, but it is commonly used extra-label in accordance with AMDUCA (Animal Medicinal Drug Use Clarification Act). Extra-label use in food animals requires a valid veterinary-client-patient relationship and extended withdrawal times must be observed. Use in minor species may be allowed under the Minor Use and Minor Species (MUMS) Act.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Itraconazole is a valuable triazole antifungal in veterinary medicine, particularly for dermatophytosis and systemic mycoses. It is generally well-tolerated, but hepatotoxicity is a concern, especially with prolonged therapy. Baseline and periodic monitoring of liver enzymes is recommended. Administer with food to enhance absorption. In cats, the oral solution is preferred due to better bioavailability and palatability. Drug interactions are significant due to CYP3A4 inhibition; review the patient's medication list. For food animals, extra-label use requires careful consideration of withdrawal times. In horses, oral absorption is poor; consider alternative formulations or routes. Always follow current guidelines and consult a veterinary pharmacologist for complex cases.

References & Literature

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