Desoxycorticosterone Pivalate

Mineralocorticoid Corticosteroid (mineralocorticoid)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IM or SC Initial: 2.2 mg/kg (1 mg/lb) every 25 days; adjust dose based on serum electrolyte levels. Maintenance: 1.5-2.2 mg/kg every 21-30 days. Every 21-30 days Duration: Lifelong therapy
Notes: Monitor serum sodium and potassium levels at 1-2 weeks after initial dose and then every 3-4 months. Adjust dose or interval to maintain electrolytes within normal limits.
Cat IM or SC Initial: 2.2 mg/kg every 25 days; adjust based on electrolytes. Typical maintenance: 12.5-25 mg per cat every 21-30 days. Every 21-30 days Duration: Lifelong therapy
Notes: Use with caution; cats may require lower doses. Monitor electrolytes closely.

Clinical Indications & Species Uses

General Indications
  • Replacement therapy for mineralocorticoid deficiency in hypoadrenocorticism
Dog (Canine)
  • Replacement therapy for primary adrenocortical insufficiency (Addison's disease)
  • Maintenance of electrolyte balance in hypoadrenocorticism
Cat (Feline)
  • Replacement therapy for primary adrenocortical insufficiency (Addison's disease) (less common but used off-label)

Pharmacology & Mechanism of Action

Drug Class: Mineralocorticoid | Pharmacological Group: Corticosteroid (mineralocorticoid)

Mechanism of Action: Desoxycorticosterone pivalate (DOCP) is a synthetic mineralocorticoid that acts on the distal convoluted tubules and collecting ducts of the kidney to increase sodium reabsorption and potassium excretion. It binds to the mineralocorticoid receptor, leading to increased expression of the sodium-potassium ATPase and epithelial sodium channels, thereby promoting sodium and water retention and enhancing potassium excretion. This helps to correct the electrolyte imbalances and hypovolemia associated with primary adrenocortical insufficiency (Addison's disease).

Pharmacodynamics: DOCP has potent mineralocorticoid activity with minimal glucocorticoid effects. It effectively replaces the deficient mineralocorticoid in animals with hypoadrenocorticism, restoring normal sodium and potassium balance, blood pressure, and cardiac output. The onset of action is slow due to the pivalate ester, which provides a prolonged duration of action. Maximal effects on electrolyte balance are typically seen within 1-2 weeks after injection.

⚡ Pharmacokinetics Summary

Absorption: DOCP is administered as a microcrystalline suspension for intramuscular or subcutaneous injection. Absorption is slow and sustained, allowing for a prolonged duration of action. Peak plasma concentrations are not typically measured, but the clinical effect lasts for approximately 21-30 days in dogs.
Distribution: DOCP is widely distributed in the body, with a volume of distribution that is not well characterized. It is highly protein-bound, primarily to corticosteroid-binding globulin and albumin.
Metabolism: DOCP is metabolized in the liver, primarily by reduction and conjugation. The pivalate ester is hydrolyzed to release the active desoxycorticosterone, which is then further metabolized.
Excretion: Metabolites are excreted primarily in the urine, with some elimination via bile and feces. The elimination half-life is prolonged due to the slow release from the injection site.
Half-Life: The effective half-life is approximately 21-30 days in dogs, corresponding to the duration of clinical effect. The plasma half-life of desoxycorticosterone itself is short (minutes), but the pivalate ester provides a depot effect.
Bioavailability: Bioavailability is complete when administered parenterally as the suspension, but the rate of absorption is slow and sustained.
Protein Binding: Desoxycorticosterone is approximately 90% bound to plasma proteins, primarily corticosteroid-binding globulin and albumin.

Available Formulations & Strengths

Injectable Suspension 25 mg/mL (IM or SC)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to desoxycorticosterone pivalate or any component of the formulation
  • Animals with congestive heart failure, severe renal disease, or hypertension (may exacerbate fluid retention)
  • Use in animals with hyperadrenocorticism (Cushing's disease) is contraindicated
Warnings & Clinical Precautions:
  • Use with caution in animals with cardiac disease, renal insufficiency, or hepatic disease.
  • May cause hypertension, edema, and weight gain due to sodium retention.
  • Do not use in pregnant or lactating animals unless the benefits outweigh the risks.
  • Monitor serum electrolytes (sodium, potassium) and blood pressure regularly.
  • May require concurrent glucocorticoid replacement (e.g., prednisone) in animals with Addison's disease, as DOCP has minimal glucocorticoid activity.
  • Shake the vial well before use to ensure uniform suspension.
  • Use aseptic technique when administering.

Adverse Effects & Reactions

Common:

  • Polyuria
  • Polydipsia
  • Increased appetite
  • Lethargy
  • Injection site reactions (pain, swelling)

Serious / Severe:

  • Hypertension
  • Congestive heart failure
  • Pulmonary edema
  • Hypernatremia
  • Hypokalemia
  • Muscle weakness
  • Cardiac arrhythmias

Rare:

  • Allergic reactions (urticaria, anaphylaxis)
  • Hyperadrenocorticism-like signs (with overdosage)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Potassium-sparing diuretics (e.g., spironolactone) May increase the risk of hyperkalemia; monitor potassium levels. High
Corticosteroids (e.g., prednisone) Additive mineralocorticoid effects may occur; monitor for electrolyte imbalances. Moderate
Amphotericin B May increase the risk of hypokalemia; monitor potassium levels. Moderate
Insulin May alter glucose metabolism; monitor blood glucose. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Hypertension
  • Edema
  • Weight gain
  • Hypernatremia
  • Hypokalemia
  • Muscle weakness
  • Cardiac arrhythmias
  • Congestive heart failure

Emergency Treatment Protocol: Discontinue the drug and provide supportive care. Monitor serum electrolytes and blood pressure. Administer fluids cautiously to correct dehydration without exacerbating fluid overload. In severe cases, administer potassium supplements if hypokalemia is present, and consider diuretics (e.g., furosemide) to manage fluid overload. Treatment is symptomatic and supportive.

Food Animal Withdrawal Times

Not approved for use in food animals; withdrawal times not established. Do not use in animals intended for food production.

Storage, Handling & Regulatory Information

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

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

Handling & Special Conditions: Protect from light. Do not freeze. Keep out of reach of children.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs in the United States (e.g., Percorten-V). Not approved for cats but used off-label.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is prohibited. For companion animals, extra-label use may be allowed under the Animal Medicinal Drug Use Clarification Act (AMDUCA) with a valid veterinarian-client-patient relationship.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Desoxycorticosterone pivalate (DOCP) is the preferred mineralocorticoid replacement for long-term management of canine hypoadrenocorticism (Addison's disease). It provides a steady release of mineralocorticoid activity over 3-4 weeks, reducing the frequency of injections compared to fludrocortisone. However, it does not provide glucocorticoid activity, so most dogs also require glucocorticoid supplementation (e.g., prednisone) at physiologic doses. Initial dosing is based on body weight, but subsequent doses should be adjusted based on serum sodium and potassium concentrations measured 1-2 weeks after injection. The goal is to maintain electrolytes within normal limits without causing hypertension or edema. In cats, DOCP is used off-label and may require lower doses. Regular monitoring of electrolytes, blood pressure, and clinical signs is essential. Client education should emphasize the need for lifelong therapy and the importance of not missing doses. If an animal presents with an Addisonian crisis, immediate treatment with intravenous fluids, glucocorticoids, and supportive care is necessary before starting maintenance therapy with DOCP.

References & Literature

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