Cortisone Acetate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-2 mg/kg/day (anti-inflammatory); 0.25-0.5 mg/kg/day (replacement therapy)	q12h or divided q12h	Duration: Variable; taper for chronic therapy Notes: For Addison's disease, combine with fludrocortisone or desoxycorticosterone pivalate.
Cat	PO	0.5-2 mg/kg/day (anti-inflammatory); 0.25-0.5 mg/kg/day (replacement therapy)	q12h or divided q12h	Duration: Variable; taper for chronic therapy Notes: Cats are more sensitive to adverse effects; use lowest effective dose.
Horse	IM	0.5-1 mg/kg	q24h	Duration: 3-5 days Notes: Use with caution; alternative corticosteroids preferred.
Cattle	IM	0.5-1 mg/kg	q24h	Duration: 3-5 days Notes: For ketosis, use as adjunct to glucose; observe withdrawal times.
Small Ruminants	IM	0.5-1 mg/kg	q24h	Duration: 3-5 days Notes: Off-label use; observe withdrawal times.
Rabbit	PO	0.5-2 mg/kg	q12-24h	Duration: Short-term; taper Notes: Use with extreme caution; rabbits are prone to GI ulceration and immunosuppression.
Bird/Poultry	IM	0.5-2 mg/kg	q12-24h	Duration: Short-term Notes: Use with caution; immunosuppression may predispose to infections.
Exotic/Other	PO/IM	0.5-2 mg/kg	q12-24h	Duration: Short-term Notes: Use with caution; species-specific sensitivities.

Clinical Indications & Species Uses

General Indications

Adrenocortical insufficiency (Addison's disease) – replacement therapy
Inflammatory and allergic conditions – anti-inflammatory and immunosuppressive therapy

Dog (Canine)

Replacement therapy for adrenocortical insufficiency (Addison's disease) in combination with mineralocorticoids
Anti-inflammatory and immunosuppressive therapy for various inflammatory, allergic, and autoimmune conditions (e.g., allergic dermatitis, asthma, immune-mediated hemolytic anemia, inflammatory bowel disease)

Cat (Feline)

Replacement therapy for adrenocortical insufficiency
Anti-inflammatory and immunosuppressive therapy for inflammatory and allergic conditions (e.g., asthma, allergic dermatitis, eosinophilic granuloma complex)

Horse (Equine)

Anti-inflammatory therapy for musculoskeletal conditions (e.g., arthritis, bursitis) – though less commonly used than other corticosteroids
Treatment of allergic reactions and inflammatory conditions

Cattle (Bovine)

Anti-inflammatory therapy for conditions such as ketosis (as an adjunct to glucose therapy) and musculoskeletal inflammation

Small Ruminants (Sheep / Goat)

Anti-inflammatory therapy for musculoskeletal and allergic conditions (off-label use)

Rabbit & Small Mammals

Anti-inflammatory and immunosuppressive therapy (off-label use) for conditions such as encephalitozoonosis (in combination with antiparasitics) and inflammatory conditions

Avian & Poultry

Anti-inflammatory therapy for shock and inflammatory conditions (off-label use)

Exotic & Other Species

Reptiles: anti-inflammatory therapy (off-label use)
Small mammals (ferrets, guinea pigs): anti-inflammatory therapy (off-label use)

Pharmacology & Mechanism of Action

Drug Class: Corticosteroid | Pharmacological Group: Glucocorticoid

Mechanism of Action: Cortisone acetate is a prodrug that is converted by hepatic 11-beta-hydroxysteroid dehydrogenase type 1 to the active metabolite hydrocortisone (cortisol). Hydrocortisone binds to the glucocorticoid receptor, leading to translocation into the nucleus and modulation of gene transcription. This results in anti-inflammatory, immunosuppressive, and metabolic effects. It induces lipocortin synthesis, which inhibits phospholipase A2, reducing arachidonic acid release and subsequent prostaglandin and leukotriene production. It also inhibits cytokine production (e.g., IL-1, IL-2, TNF-alpha), reduces neutrophil and macrophage migration, and stabilizes lysosomal membranes.

Pharmacodynamics: Cortisone acetate has predominantly glucocorticoid activity with minimal mineralocorticoid activity (about 0.8 times that of hydrocortisone). It produces anti-inflammatory effects by suppressing the inflammatory response to various inciting agents, inhibiting edema, fibrin deposition, capillary dilation, leukocyte migration, and phagocytosis. It also suppresses the immune system by reducing lymphocyte proliferation and antibody production. Metabolic effects include increased gluconeogenesis, protein catabolism, and lipolysis. It also affects the hypothalamic-pituitary-adrenal axis, leading to adrenal suppression with prolonged use.

⚡ Pharmacokinetics Summary

Absorption: Cortisone acetate is well absorbed after oral administration, but it is poorly absorbed after intramuscular injection due to its acetate ester, which requires hydrolysis. Oral absorption is rapid, with peak plasma levels occurring within 1-2 hours. The bioavailability is approximately 25% due to extensive first-pass metabolism to hydrocortisone.

Distribution: Cortisone and its active metabolite hydrocortisone are widely distributed throughout the body. They cross the placenta and are excreted in milk. They are bound to plasma proteins, primarily corticosteroid-binding globulin (CBG) and albumin, with about 90% bound at therapeutic concentrations.

Metabolism: Cortisone acetate is rapidly hydrolyzed to cortisone, which is then converted to hydrocortisone (cortisol) in the liver and adipose tissue. Hydrocortisone is further metabolized in the liver to inactive metabolites such as tetrahydrocortisol and glucuronide conjugates.

Excretion: Metabolites are excreted primarily in the urine as glucuronide and sulfate conjugates. A small amount is excreted in feces. The elimination half-life of cortisone is short, but the biological half-life (duration of action) is longer due to intracellular effects.

Half-Life: Plasma half-life: approximately 30 minutes in dogs and cats; biological half-life: 8-12 hours.

Bioavailability: Oral bioavailability is approximately 25% due to first-pass metabolism; IM bioavailability is variable and slow.

Protein Binding: Approximately 90% bound to plasma proteins (CBG and albumin).

Available Formulations & Strengths

Oral Tablet 5 mg, 10 mg, 25 mg (PO)

Injectable Suspension 25 mg/mL, 50 mg/mL (IM)

Contraindications & Clinical Warnings

Contraindications:

Systemic fungal infections
Known hypersensitivity to corticosteroids
Administration of live vaccines (immunosuppression may impair immune response)
Gastrointestinal ulceration (may exacerbate)
Osteoporosis (may worsen)
Pregnancy (especially first trimester; may cause fetal abnormalities)
Concurrent use with NSAIDs (increased risk of GI ulceration)

Warnings & Clinical Precautions:

Use with caution in animals with diabetes mellitus, renal disease, heart disease, hypertension, or epilepsy.
Prolonged use may cause iatrogenic hyperadrenocorticism (Cushing's syndrome).
Abrupt withdrawal after prolonged therapy may precipitate adrenal insufficiency; taper dose gradually.
Use with caution in pregnant animals; potential teratogenic effects.
May mask signs of infection; monitor for intercurrent infections.
In food animals, observe withdrawal times.
In horses, use with caution in animals with laminitis risk.
In rabbits and rodents, corticosteroids are generally contraindicated due to high risk of adverse effects.

Adverse Effects & Reactions

Common:

Increased thirst and urination (polydipsia/polyuria)
Increased appetite
Panting (in dogs)
Weight gain
Behavioral changes (e.g., lethargy or agitation)

Serious / Severe:

Iatrogenic hyperadrenocorticism (Cushing's syndrome) with prolonged use
Adrenal suppression and atrophy
Gastrointestinal ulceration and perforation
Diabetes mellitus or worsening of glycemic control
Immunosuppression leading to opportunistic infections
Ligament and tendon rupture (in horses)
Laminitis (in horses)
Growth retardation in young animals

Rare:

Pancreatitis
Hepatopathy
Cutaneous calcinosis
Behavioral changes (aggression, depression)
Anaphylactoid reactions (rare)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Nonsteroidal anti-inflammatory drugs (NSAIDs)	Increased risk of gastrointestinal ulceration and bleeding.	High
Phenobarbital or phenytoin	Increased hepatic metabolism of corticosteroids, reducing their efficacy.	Moderate
Insulin or oral hypoglycemic agents	Corticosteroids antagonize the hypoglycemic effects, requiring dose adjustments.	Moderate
Diuretics (e.g., furosemide, thiazides)	Increased risk of hypokalemia.	Moderate
Amphotericin B	Increased risk of hypokalemia and potential cardiac toxicity.	Moderate
Vaccines (live)	Immunosuppression may reduce vaccine efficacy and increase risk of vaccine-induced disease.	High
Cyclosporine	Additive immunosuppression; may increase risk of infections.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Polydipsia, polyuria, polyphagia
Gastrointestinal ulceration and hemorrhage
Hyperglycemia and glycosuria
Electrolyte imbalances (hypokalemia, hypernatremia)
Hypertension
Behavioral changes (excitement or depression)
Adrenal suppression (with chronic overdose)

Emergency Treatment Protocol: Treatment is primarily supportive. For acute overdose, induce vomiting (if oral and within 2 hours) and administer activated charcoal. Monitor vital signs, electrolytes, and blood glucose. Provide symptomatic treatment for GI ulceration (e.g., H2 antagonists or proton pump inhibitors). For chronic overdose, taper the drug gradually to avoid adrenal crisis. In severe cases, consider administration of mineralocorticoids if adrenal insufficiency occurs. There is no specific antidote.

Food Animal Withdrawal Times

🥩 Meat: 21 days🥛 Milk: 3 days

Withdrawal times vary by country and formulation; consult local regulations. For cattle and small ruminants, meat withdrawal is typically 21 days and milk withdrawal 3 days. Not approved for use in poultry or egg-laying birds in many jurisdictions.

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 injectable suspension.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats for oral and injectable formulations. Not approved for food animals in the US, but may be used extra-label.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship, provided withdrawal times are extended and residues are avoided. Use in non-food animals is allowed. In the EU, similar rules apply under Regulation (EU) 2019/6.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Cortisone acetate is a short-acting glucocorticoid with mineralocorticoid activity. It is primarily used for replacement therapy in Addison's disease and as an anti-inflammatory agent. Because it requires hepatic activation to hydrocortisone, it may be less effective in animals with severe hepatic disease. It is less potent than prednisone/prednisolone and has a shorter duration of action. For anti-inflammatory purposes, other corticosteroids such as prednisone or dexamethasone are often preferred. In dogs and cats, oral administration is common; IM administration is painful and absorption is erratic. In horses, it is rarely used due to the risk of laminitis. In food animals, use is limited by withdrawal times. Always taper the dose after prolonged therapy to avoid adrenal crisis. Monitor for adverse effects, especially with chronic use. For Addison's disease, combine with a mineralocorticoid (e.g., fludrocortisone or DOCP).

References & Literature

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