Posaconazole — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	5-10 mg/kg	q12h for first 24 hours, then q24h	Duration: Variable; often 4-6 months or longer depending on infection and response Notes: Administer with food to enhance absorption. Use the oral suspension or tablets; tablets have better bioavailability. Monitor liver enzymes and therapeutic drug levels if available.
Cat	PO	5-10 mg/kg	q12h for first 24 hours, then q24h	Duration: Variable; often 4-6 months or longer Notes: Administer with food. Cats may be more prone to adverse effects; monitor appetite and liver enzymes.
Horse	PO	2-4 mg/kg	q24h	Duration: Variable; often weeks to months Notes: Limited pharmacokinetic data; use with caution. May require higher doses for guttural pouch mycosis.
Rabbit	PO	5-10 mg/kg	q24h	Duration: Variable Notes: Extrapolated from other species; use with caution.
Bird (pet)	PO	5-10 mg/kg	q12h	Duration: Variable Notes: Limited data; use with caution. May be compounded into suspensions.

Clinical Indications & Species Uses

General Indications

Treatment of systemic fungal infections caused by susceptible fungi, especially Aspergillus spp., Candida spp., and zygomycetes.
Prophylaxis of invasive fungal infections in immunocompromised patients.

Dog (Canine)

Treatment of systemic fungal infections including aspergillosis (nasal and disseminated), blastomycosis, histoplasmosis, coccidioidomycosis, cryptococcosis, and zygomycosis.
Treatment of refractory or resistant fungal infections when other azoles have failed.
Prophylaxis in immunocompromised dogs (e.g., those on immunosuppressive therapy).

Cat (Feline)

Treatment of systemic fungal infections including cryptococcosis, histoplasmosis, blastomycosis, sporotrichosis, and aspergillosis.
Treatment of refractory dermatophytosis (though not first-line).

Horse (Equine)

Treatment of fungal infections such as aspergillosis (guttural pouch mycosis), histoplasmosis, and other systemic mycoses.
Used off-label due to limited approved veterinary formulations.

Rabbit & Small Mammals

Treatment of systemic fungal infections such as aspergillosis and dermatophytosis (off-label).

Avian & Poultry

Treatment of aspergillosis in pet birds (e.g., parrots, raptors) and potentially in poultry, but not approved for food animals.

Exotic & Other Species

Treatment of fungal infections in reptiles (e.g., snakes with fungal pneumonia), small mammals (e.g., ferrets, guinea pigs), and other exotic species (off-label).

Pharmacology & Mechanism of Action

Drug Class: Triazole antifungal | Pharmacological Group: Azole antifungals

Mechanism of Action: Posaconazole inhibits fungal cytochrome P450-dependent enzyme lanosterol 14α-demethylase, which is essential for the conversion of lanosterol to ergosterol, a key component of the fungal cell membrane. This leads to accumulation of toxic methylated sterols and depletion of ergosterol, disrupting membrane integrity and function, resulting in fungal cell death. It is primarily fungistatic but may be fungicidal against certain species at high concentrations.

Pharmacodynamics: Posaconazole exhibits broad-spectrum antifungal activity against yeasts, molds, and dimorphic fungi, including Aspergillus spp., Candida spp., Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, and the zygomycetes (e.g., Rhizopus, Mucor). It is more potent than itraconazole and voriconazole against many molds, especially Aspergillus and zygomycetes. It also has activity against some parasites (e.g., Leishmania) but is not primarily used for that. Resistance can develop via mutations in the target enzyme or overexpression of efflux pumps.

⚡ Pharmacokinetics Summary

Absorption: Posaconazole is administered orally (tablets or oral suspension). Absorption is variable and influenced by food, especially high-fat meals, which increase absorption. The oral suspension has lower and more variable bioavailability compared to the delayed-release tablets. In dogs, oral bioavailability is approximately 30-50% with the suspension, but higher with the tablet formulation. In cats, absorption is also variable; administration with food improves absorption.

Distribution: Posaconazole has a large volume of distribution, indicating extensive tissue penetration. It distributes well into lungs, liver, kidney, spleen, and adrenal glands. Penetration into the CNS is limited but may be sufficient for some fungal infections. It is highly protein-bound (greater than 98%) in plasma, primarily to albumin.

Metabolism: Posaconazole is metabolized primarily in the liver via glucuronidation (UDP-glucuronosyltransferase) and to a lesser extent by oxidative metabolism (CYP3A4). It is a strong inhibitor of CYP3A4, which can lead to significant drug interactions. It does not undergo extensive CYP-mediated metabolism itself, so its own metabolism is less affected by CYP inhibitors/inducers.

Excretion: Posaconazole is excreted primarily in feces as unchanged drug (about 77%) and metabolites (about 17%). Renal excretion is minimal (less than 1% unchanged). Biliary excretion is a major route. In animals with hepatic impairment, clearance may be reduced.

Half-Life: The elimination half-life in dogs is approximately 25-30 hours; in cats, it is approximately 24-30 hours. In humans, it is about 35 hours, but in animals, it may vary.

Bioavailability: Oral bioavailability is variable: in dogs, approximately 30-50% for suspension, higher for tablets; in cats, approximately 30-40% for suspension; administration with food increases absorption.

Protein Binding: Greater than 98% protein bound in plasma.

Available Formulations & Strengths

Oral Suspension 40 mg/mL (PO)

Delayed-Release Tablet 100 mg (PO)

Intravenous Solution (not commonly used in veterinary medicine) 18 mg/mL (IV)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to posaconazole or other azole antifungals.
Concurrent use with drugs that are highly dependent on CYP3A4 for metabolism (e.g., certain statins, midazolam, pimozide) due to risk of severe toxicity.
Use in pregnant or lactating animals unless benefits outweigh risks (teratogenic in some species).

Warnings & Clinical Precautions:

Use with caution in animals with hepatic impairment; monitor liver enzymes regularly.
Use with caution in animals with cardiac disease, as QT prolongation may occur.
May cause gastrointestinal upset; administer with food to reduce nausea.
In cats, monitor for anorexia and weight loss; may require dose adjustment.
Drug interactions are common; review all concurrent medications.
Not approved for food animals; withdrawal times are not established.

Adverse Effects & Reactions

Common:

Gastrointestinal upset (vomiting, diarrhea, anorexia)
Elevated liver enzymes (ALT, AST, ALP)
Hypokalemia
Headache (in humans, but may be observed in animals as lethargy)

Serious / Severe:

Hepatotoxicity (hepatic necrosis, jaundice)
QT prolongation and cardiac arrhythmias
Adrenal insufficiency (rare)
Severe skin reactions (e.g., Stevens-Johnson syndrome, rare)

Rare:

Peripheral neuropathy
Visual disturbances
Photosensitivity
Bone marrow suppression

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CYP3A4 substrates (e.g., cyclosporine, tacrolimus, midazolam, cisapride, pimozide)	Posaconazole inhibits CYP3A4, increasing plasma concentrations of these drugs, potentially leading to toxicity.	High
Rifampin, rifabutin, phenytoin, carbamazepine	These CYP3A4 inducers decrease posaconazole plasma concentrations, reducing efficacy.	High
H2 antagonists and proton pump inhibitors (e.g., omeprazole)	May decrease absorption of posaconazole suspension (but not tablets) by reducing gastric acidity.	Moderate
Vincristine and other vinca alkaloids	Increased risk of neurotoxicity due to CYP3A4 inhibition.	Moderate
Digoxin	Posaconazole may increase digoxin levels; monitor digoxin concentrations.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

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

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 (especially potassium), and cardiac function (ECG). Provide intravenous fluids and supportive care. In severe cases, consider hemodialysis (though unlikely to be effective due to high protein binding).

Food Animal Withdrawal Times

Not approved for use in food animals. Withdrawal times have not been established. Do not use in animals intended for human consumption.

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).

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

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not approved for veterinary use in the US; approved for human use (e.g., Noxafil).

Extra-Label (Off-Label) Use: In the US, posaconazole is not FDA-approved for veterinary use. Use in animals is extra-label and must comply with AMDUCA (Animal Medicinal Drug Use Clarification Act) regulations. For food animals, extra-label use is prohibited if there are no established withdrawal times and if approved drugs are available.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Posaconazole is a potent broad-spectrum triazole antifungal that is particularly valuable for treating resistant or refractory fungal infections, especially aspergillosis and zygomycosis. It is often used when other azoles (e.g., itraconazole, voriconazole) have failed or are not tolerated. Due to its high cost and potential for drug interactions, it should be reserved for cases where susceptibility testing indicates susceptibility or when other options are limited. Therapeutic drug monitoring is recommended in humans and may be beneficial in animals to ensure adequate exposure and minimize toxicity. Administer with food to enhance absorption, and monitor liver enzymes and electrolytes periodically. In cats, watch for anorexia and weight loss. Because of the lack of approved veterinary formulations, compounded preparations may be necessary, but their stability and bioavailability should be verified. Always consider the potential for drug interactions, especially with CYP3A4 substrates. For food animals, do not use due to lack of withdrawal data.

References & Literature

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