Aglepristone

Antiprogestin Progesterone receptor antagonist

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog SC 10 mg/kg Once daily for 2 consecutive days Duration: 2 days
Notes: For pregnancy termination: administer on days 0 and 1. For mammary tumors: repeat after 1-2 weeks if needed.
Cat SC 10 mg/kg Once daily for 2 consecutive days Duration: 2 days
Notes: For pregnancy termination: administer on days 0 and 1. Efficacy is higher if given early (before day 30).

Clinical Indications & Species Uses

General Indications
  • Termination of pregnancy in dogs and cats
  • Treatment of progesterone-dependent conditions
Dog (Canine)
  • Termination of pregnancy (up to 45 days after mating)
  • Treatment of mammary tumors (benign and malignant)
  • Treatment of false pregnancy (pseudopregnancy)
  • Induction of parturition (in selected cases)
Cat (Feline)
  • Termination of pregnancy (up to 30 days after mating)
  • Treatment of mammary tumors (limited data)

Pharmacology & Mechanism of Action

Drug Class: Antiprogestin | Pharmacological Group: Progesterone receptor antagonist

Mechanism of Action: Aglepristone is a synthetic steroid that acts as a competitive antagonist at the progesterone receptor. By binding to the receptor with high affinity but without activating the receptor, it blocks the effects of endogenous progesterone. This action is used to terminate pregnancy by causing luteolysis, cervical dilation, and expulsion of the conceptus. It also inhibits the action of progesterone in the mammary gland, which is useful in treating mammary tumors.

Pharmacodynamics: Aglepristone has a strong affinity for the progesterone receptor, with minimal androgenic, estrogenic, or glucocorticoid activity. It induces a rapid decline in plasma progesterone concentrations, leading to luteolysis and termination of pregnancy. In non-pregnant animals, it can be used to treat conditions associated with progesterone dominance, such as mammary tumors and certain skin disorders. Its effects are dose-dependent and reversible upon discontinuation.

⚡ Pharmacokinetics Summary

Absorption: After subcutaneous administration, aglepristone is rapidly absorbed, reaching peak plasma concentrations within 1-2 hours. Bioavailability is high, approximately 100%.
Distribution: Aglepristone is widely distributed throughout the body, with high concentrations in the liver, kidneys, and reproductive organs. It crosses the placenta and is excreted in milk.
Metabolism: Aglepristone is extensively metabolized in the liver, primarily by hydroxylation and conjugation. The main metabolites are less active than the parent compound.
Excretion: Metabolites are excreted primarily in the feces via bile, with a smaller amount in the urine. The elimination half-life is approximately 24-48 hours in dogs.
Half-Life: Dogs: ~24-48 hours; Cats: ~24 hours (estimated)
Bioavailability: ~100% after subcutaneous injection
Protein Binding: Approximately 90% bound to plasma proteins, mainly albumin.

Available Formulations & Strengths

Injectable Solution 30 mg/mL (SC)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to aglepristone or any component of the formulation
  • Use in animals with hepatic or renal impairment
  • Use in pregnant animals beyond the recommended gestational age (dogs >45 days, cats >30 days)
  • Use in animals with uterine infection or metritis
  • Use in animals with a history of thromboembolic disease
Warnings & Clinical Precautions:
  • Use with caution in animals with diabetes mellitus, as aglepristone may affect glucose metabolism.
  • May cause transient local reactions at the injection site.
  • In lactating animals, aglepristone is excreted in milk; do not use in nursing animals unless the benefits outweigh the risks.
  • Safety in breeding animals has not been fully established; use with caution in valuable breeding stock.
  • Do not use in animals intended for breeding for at least one estrous cycle after treatment.
  • In food animals, aglepristone is not approved; extra-label use is prohibited in the US.

Adverse Effects & Reactions

Common:

  • Local injection site reactions (pain, swelling)
  • Vomiting
  • Lethargy
  • Decreased appetite

Serious / Severe:

  • Uterine infection (metritis) if pregnancy termination is incomplete
  • Hemorrhage
  • Anaphylaxis (rare)
  • Hepatotoxicity (rare)

Rare:

  • Mammary gland enlargement
  • Alopecia
  • Behavioral changes

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Corticosteroids May enhance the catabolic effects of corticosteroids; monitor for signs of hypercortisolism. Moderate
Progestins (e.g., megestrol acetate) May antagonize the effects of progestins; concurrent use is not recommended. High
Ketoconazole May increase plasma concentrations of aglepristone due to CYP inhibition; monitor for increased adverse effects. Moderate
Phenobarbital May decrease plasma concentrations of aglepristone due to CYP induction; monitor for reduced efficacy. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Lethargy
  • Hypotension
  • Electrolyte imbalances

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce vomiting if recent ingestion (oral) and administer activated charcoal. Monitor vital signs and provide fluid therapy as needed. In severe cases, consider hospitalization.

Food Animal Withdrawal Times

Not approved for use in food animals. Extra-label use is prohibited in the US. No withdrawal times established.

Storage, Handling & Regulatory Information

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

Handling & Special Conditions: Protect from freezing. Keep in original carton until use.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use in the US; approved in some European countries (e.g., UK, France) for dogs and cats.

Extra-Label (Off-Label) Use: In the US, aglepristone is not FDA-approved for veterinary use; it is available through extra-label use under AMDUCA for dogs and cats. In Europe, it is approved for use in dogs and cats. Extra-label use in food animals is prohibited.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Aglepristone is a valuable tool for terminating unwanted pregnancies in dogs and cats, especially when surgical intervention is not desired. It is most effective when administered early in gestation. For pregnancy termination, a two-dose protocol (10 mg/kg SC on two consecutive days) is standard. It is also used off-label for treating mammary tumors and false pregnancy. Adverse effects are generally mild and transient, but serious complications such as metritis can occur if pregnancy termination is incomplete. Always confirm pregnancy status before administration and perform follow-up ultrasound to ensure complete termination. In the US, it is not FDA-approved, so informed consent and careful client communication are essential.

References & Literature

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