Aglepristone

Overview

Aglepristone (Alizin®, Alizine®) is a synthetic progesterone receptor antagonist used in veterinary medicine primarily for medical termination of pregnancy and other progesterone-dependent conditions in several animal species. It is formulated as an injectable preparation and is marketed for use in dogs in multiple countries outside the United States.

By competitively blocking progesterone receptors, aglepristone disrupts the hormonal support required to maintain pregnancy, resulting in embryonic resorption, abortion, or induction of parturition depending on the stage of gestation and clinical application. In dogs, pregnancy termination typically occurs within 4 to 7 days after administration.

In addition to pregnancy termination, aglepristone has been used extra-label in dogs and cats for the medical management of progesterone-dependent disorders, including pyometra, mammary fibroadenomatous hyperplasia in cats, and selected reproductive or endocrine conditions in dogs.

Mechanism of Action (MOA): Aglepristone competitively antagonizes progesterone at the progesterone (P4) receptor. It has a higher affinity for progesterone receptors than endogenous progesterone, particularly in dogs and cats. Although it blocks progesterone action at the tissue level, it does not significantly alter circulating progesterone concentrations. Aglepristone also binds to glucocorticoid receptors without exerting glucocorticoid activity, potentially interfering with glucocorticoid signaling.

Indications

Aglepristone is used in veterinary medicine primarily for conditions that are dependent on progesterone activity. Its clinical applications vary by species and are largely extra-label, except where specifically licensed in certain countries.

• Pregnancy termination (dogs): Labeled in several countries for termination of pregnancy in bitches up to 45 days after mating. It is nearly 100% effective in preventing implantation during early pregnancy and approximately 95% effective for termination during midterm gestation.
• Induction of parturition (dogs): Used extra-label, often in combination with oxytocin, to induce parturition near term when fetal maturity has been confirmed.
• Pyometra complex (dogs and cats): Used as part of a medical management protocol for open-cervix pyometra, frequently in combination with prostaglandin analogs and antimicrobial therapy, in clinically stable patients where surgery is not immediately indicated.
• Pregnancy termination (cats): Used extra-label for abortion in queens, with variable efficacy when used alone; combination therapy with other agents may improve success rates.
• Mammary fibroadenomatous hyperplasia (cats): Used to induce regression of progesterone-dependent mammary enlargement.
• Endocrine and reproductive disorders (dogs): Extra-label uses include treatment of progesterone-induced insulin-resistant diabetes mellitus, progesterone-induced acromegaly, benign vaginal tumors, and progesterone receptor–positive mammary carcinomas.
• Other species (extra-label): Used for parturition induction in ewes and prevention of fetal implantation in rabbits under controlled clinical or research settings.

Dosage (Reference)

Dog

In dogs, aglepristone is administered by subcutaneous injection only. All indications listed below are considered extra-label in many regions and require confirmation of diagnosis, appropriate case selection, and close follow-up.

Cat

In cats, aglepristone is used extra-label for progesterone-dependent reproductive disorders. Response rates vary, and combination therapy is commonly required to improve efficacy.

Warnings & Precautions

Aglepristone is a potent progesterone receptor antagonist with additional activity at glucocorticoid receptors. Proper case selection, strict handling precautions, and close clinical monitoring are essential to minimize risks and ensure safe use.

• Pregnancy handling risk: This medication must not be handled or administered by pregnant women, as accidental exposure may induce abortion.
• Use during pregnancy: Contraindicated in pregnant animals unless the explicit goal is pregnancy termination or induction of parturition.
• Systemic illness: Do not use in animals in poor general health or those with diabetes mellitus, or with hepatic or renal impairment.
• Adrenal function: Because aglepristone antagonizes glucocorticoid receptors, it should not be used in animals with hypoadrenocorticism or a genetic predisposition to this condition.
• Respiratory disease: Use with caution in animals with chronic obstructive airway disease.
• Cardiovascular disease: Use cautiously in animals with cardiovascular disease, particularly those with bacterial endocarditis.
• Pyometra management: Medical treatment with aglepristone is contraindicated in bitches with severe or life-threatening conditions, such as hepatorenal failure or suspected peritonitis.
• Injection technique: The drug is formulated in an oil–alcohol vehicle and should be administered subcutaneously only. Injection into the scruff of the neck is recommended to minimize local reactions.
• Injection volume: In dogs, no more than 5 mL should be injected at a single site to reduce the risk of severe local inflammation.
• Post-injection care: Gentle massage of the injection site after administration is recommended by the manufacturer.

Drug Interactions

The following drug interactions with aglepristone have either been reported or are theoretical in animals or humans and may be clinically relevant in veterinary patients. Concurrent use is not always contraindicated, but potential risks should be carefully weighed and additional monitoring performed when appropriate.

• Progestins (natural or synthetic): Concurrent administration may theoretically reduce the effectiveness of both aglepristone and progestin compounds due to competitive receptor interactions.
• Glucocorticoids (e.g., prednisolone, prednisone): Aglepristone may reduce the clinical efficacy of glucocorticoid therapy by antagonizing glucocorticoid receptors.
• Ketoconazole, itraconazole, erythromycin: These drugs may interact with aglepristone, presumably through inhibition of CYP3A enzymes and/or P-glycoprotein, potentially altering aglepristone metabolism and exposure.

Side Effects & Overdose

Side Effects

Adverse effects associated with aglepristone are primarily related to its oil-alcohol injectable formulation and progesterone receptor antagonism. Most adverse effects are transient and resolve without specific treatment.

• Injection site reactions: Localized pain, inflammation, edema, skin thickening, ulceration, and regional lymph node enlargement may occur. Severity is correlated with injection volume. Reactions typically resolve within 2 to 4 weeks.
• Injection-related pain: Pain is usually short-lived and resolves shortly after administration. Light massage of the injection site is recommended.
• Gastrointestinal effects: Anorexia, diarrhea, and vomiting have been reported.
• Behavioral changes: Excitation, restlessness, or depression may occur following treatment.
• Uterine infections: Reported in a small percentage of treated animals, particularly when used for pregnancy termination or pyometra management.
• Cardiovascular effects (cats): Tachycardia has been reported in cats treated for mammary fibroadenomatous hyperplasia.
• Hematologic and biochemical changes: Transient and reversible changes may include neutrophilia or neutropenia, thrombocytosis, variations in hematocrit, lymphocytosis or lymphopenia, and elevations in BUN, creatinine, electrolytes, and liver enzymes (ALT, ALP, AST).
• Reproductive-related effects: When used for pregnancy termination, brown mucoid vaginal discharge may occur approximately 24 hours before fetal expulsion and may persist for 3 to 5 days. Signs associated with parturition (e.g., mammary congestion, lactation, restlessness) may occur if used after day 20 of gestation.

Overdose

Aglepristone has demonstrated a wide margin of safety in overdose situations.

• Systemic toxicity: Administration of doses up to three times the recommended dose (30 mg/kg) did not result in significant systemic adverse effects.
• Local reactions: Increased severity of injection site reactions may occur due to larger injection volumes.
• Management: Treatment of overdose is supportive and symptomatic. Monitor injection sites and overall clinical status.
• Poison consultation: For suspected overdose cases, consultation with a veterinary poison control center is recommended for guidance and monitoring recommendations.

Key Notes

Practical clinical points to support appropriate case selection and optimize outcomes when using aglepristone in veterinary practice:

• Timing is critical: Clinical success depends heavily on accurate determination of gestational stage or luteal phase timing, particularly for pregnancy termination and parturition induction.
• Ultrasound guidance: Ultrasonography is essential for confirming pregnancy status, fetal viability, treatment success, and for monitoring complications after administration.
• Medical vs surgical decision-making: Aglepristone is best suited for clinically stable patients; surgical intervention remains the preferred option in unstable or life-threatening cases.
• Delayed clinical response: Pregnancy termination or uterine evacuation does not occur immediately and typically develops over several days; owners should be counseled accordingly.
• Fertility preservation: Unlike ovariohysterectomy, aglepristone preserves future reproductive potential when used appropriately.
• Adjunctive protocols: Therapeutic success is often enhanced when aglepristone is incorporated into multimodal treatment plans (e.g., antibiotics, prostaglandins, or dopamine agonists).
• Injection technique matters: Proper site selection, volume limitation per site, and post-injection massage significantly reduce local complications.
• Client compliance: Strict adherence to follow-up visits is critical to confirm resolution and detect complications early.
• Regulatory availability: Lack of availability in certain regions may affect access and requires legal and ethical consideration before use.