Vetdrugs 2.0Aglepristone is a steroidal antiprogestin used primarily for medical termination of pregnancy in bitches. It blocks progesterone action at the receptor rather than requiring a fall in circulating progesterone before it can work. Other veterinary applications exploit the same dependence of reproductive or mammary tissues on progesterone.
Selected feline pregnancy termination, mammary fibroadenomatous hyperplasia and medical pyometra protocols are extralabel uses. These applications share a dependence on progesterone signaling in reproductive or mammary tissues.
Group
Antiprogestin; progesterone-receptor antagonist
Mechanism of Action
Aglepristone binds with high affinity to progesterone receptors without producing the normal progestational response. Competitive receptor blockade interrupts progesterone-dependent maintenance of the endometrium and pregnancy, promotes cervical opening and permits uterine evacuation. Circulating progesterone can remain measurable despite effective blockade at its target tissue.
Progesterone also supports mammary proliferation in susceptible cats and contributes to uterine conditions that favor pyometra. Antagonizing its receptor provides a rationale for regression of progesterone-associated mammary hyperplasia and for restoring uterine drainage in selected pyometra protocols. It does not have direct antibacterial activity.
Aglepristone also binds glucocorticoid receptors and has antiglucocorticoid activity. This additional receptor action can reduce glucocorticoid effects and is distinct from progesterone blockade in reproductive tissues.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Pregnancy termination | 10 mg/kg | SC | Every 24 h | Up to 2 days; Do not use in: Desired ongoing pregnancy, More than 45 days after mating, Hepatic or renal impairment, Diabetes mellitus, Hypoadrenocorticism, Poor general health; Two injections total. Treat after the end of estrus and no later than day 45 after mating. Maximum injection volume is 5 mL per site; confirm uterine evacuation by ultrasound. |
| Pyometra | 10 mg/kg | SC | Do not use in: Peritonitis, Hepatic or renal impairment, Diabetes mellitus, Hypoadrenocorticism, Poor general health; Administer on days 1, 2, 7 and 14 as part of a selected medical treatment course with antimicrobials and supportive care. Confirm uterine evacuation and monitor for recurrence. | |
| Metritis | 10 mg/kg | SC | Do not use in: Peritonitis, Hepatic or renal impairment, Diabetes mellitus, Hypoadrenocorticism, Poor general health; Described schedule: days 1, 2 and 8, with appropriate antimicrobial and supportive treatment. Reassess uterine evacuation and systemic status. | |
| Parturition induction | 15 mg/kg | SC | Every 9 h | Do not use in: Uncertain gestational age or fetal maturity, Hepatic or renal impairment, Diabetes mellitus, Hypoadrenocorticism; Two injections total in a studied protocol beginning on or after gestational day 58. Confirm dating and fetal maturity; monitor whelping and intervene if delivery does not proceed. |
| Parturition induction | 15 mg/kg | SC | Every 24 h | Up to 2 days; Do not use in: Uncertain gestational age or fetal maturity, Hepatic or renal impairment, Diabetes mellitus, Hypoadrenocorticism; Two injections total beginning at day 60 after the estimated LH surge in the described protocol. Subsequent oxytocin is a separate regimen; this is not aglepristone monotherapy. |
| Pyometra | 6 mg/kg | SC | Closed-cervix alternative: twice on day 1, then once daily on days 2, 3 and 4. The variable schedule is not a continuous twice-daily course. Reassess systemic illness and uterine response. | |
| Pyometra | 10 mg/kg | SC | Alternative injections on days 1, 3 and 8, with possible further treatment on days 15 and 28 according to clinical status. Do not convert the gaps into a fixed daily interval. | |
| Pyometra | 10 mg/kg | SC | Combined course: aglepristone on days 1, 2 and 8; cloprostenol 1 mcg/kg SC on days 3–7. Persistent disease may require further aglepristone on days 14 and 28. Provide fluids and antibiotics according to systemic status; the described antimicrobial example is amoxicillin/clavulanate 24 mg/kg/day on days 1–5. | |
| Pyometra | 10 mg/kg | SC | Separate combined course: aglepristone on days 1, 2, 8, 15 and 29, with misoprostol 10 mcg/kg PO twice daily on days 3–12. Preserve the individual component schedules and reassess response. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Pregnancy termination | 10 mg/kg | SC | Every 24 h | Up to 2 days; Do not use in: Desired ongoing pregnancy, Pregnancy later than the second trimester; Two injections total. Extralabel; do not use later than the second trimester. Some protocols combine misoprostol, which requires a separate regimen. |
| Pyometra | 10 mg/kg | SC | Administer on days 1, 2 and 7; day 14 is used if not cured. Reassess clinically and by ultrasound; give appropriate antimicrobial and supportive treatment. | |
| Mammary fibroadenomatous hyperplasia | 20 mg/kg | SC | Every 168 h | Do not use in: Desired ongoing pregnancy; Continue to clinical resolution, commonly over 1-4 weeks; prolonged progestin exposure can require longer treatment. |
| Mammary fibroadenomatous hyperplasia | 10 mg/kg | SC | Do not use in: Desired ongoing pregnancy; Alternative course: injections on two consecutive days each week until regression; long-acting progestin-associated disease can require about five weeks. | |
| Pregnancy termination | 15 mg/kg | SC | Every 24 h | Up to 2 days; Do not use in: Desired ongoing pregnancy, Pregnancy later than the second trimester; Two injections total in a separately described feline protocol. Confirm gestational stage and completion; do not mix dose endpoints with the existing regimen. |
Indications
- Medical termination of pregnancy in bitches up to 45 days after mating.
- Extralabel pregnancy termination in queens, including selected combination protocols.
- Medical management of selected canine pyometra or metritis and feline pyometra cases, usually in combination with antimicrobial and supportive treatment.
- Treatment of progesterone-associated feline mammary fibroadenomatous hyperplasia.
- Selected induction of parturition in bitches with established gestational timing and fetal maturity.
Contraindications
- Do not use to preserve a desired pregnancy.
- For labeled canine pregnancy termination, do not administer beyond day 45 after mating.
- Do not use in dogs with hepatic or renal impairment, diabetes, poor general health, or known/latent hypoadrenocorticism or genetic predisposition to it.
- Hypersensitivity to aglepristone or excipients, including the oily vehicle.
- Accidental self-injection is particularly hazardous during human pregnancy; prevent skin exposure and self-injection.
- Do not administer to food-producing animals.
- Rule out peritonitis before medical treatment of pyometra. Severe systemic illness, deterioration or treatment failure can require ovariohysterectomy.
- Parturition induction can produce premature puppies if gestational timing or fetal maturity is incorrect.
- Mammary-hyperplasia treatment can terminate an unsuspected pregnancy; establish pregnancy status before treatment.
Interactions
- May antagonize glucocorticoid therapy.
- Potential interactions with ketoconazole, itraconazole and erythromycin have not been adequately characterized.
- Do not mix the injection with other medicines in the same syringe.
- Natural or synthetic progestins can oppose the antiprogestin effect and may reduce efficacy.
Adverse effects
- Injection-site pain, swelling, inflammation or thickening.
- Anorexia, depression, excitation, diarrhea or vomiting.
- Vaginal discharge and mammary congestion accompanying termination.
- Incomplete abortion, uterine infection or treatment failure; failure can lead to dystocia or uterine rupture.
Toxicity
High injection volumes increase local inflammation. After pregnancy termination, persistent pregnancy or retained uterine contents is clinically important even without an overdose. Confirm completion by ultrasound about 10 days after treatment and no earlier than 30 days after mating in bitches.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Alizin 30 mg/mL Oily solution containing refined arachis oil; no antimicrobial preservative. Maximum 5 mL per injection site in large bitches. Keep in the outer carton protected from light; use within 28 days after first opening. | Injection | 30 mg / mL | SC |
Monitoring and Administration
Successful treatment requires confirmation that pregnancy has ended and the uterus has emptied. It can also be part of selected medical pyometra protocols, which require close reassessment.
Monitor clinical condition, vaginal discharge, uterine contents and response to treatment. Purulent or hemorrhagic discharge, prolonged discharge beyond three weeks, or clinical deterioration requires reassessment.
Return to estrus can be earlier than expected. Long-acting progestins can prolong the course needed to resolve feline mammary hyperplasia.
In dogs, peak concentrations after the two-injection course occur about 2.5 days later, and mean residence time is about 6 days; excretion is predominantly fecal.
Accidental self-injection may cause severe pain, swelling and ischemic injury, and may induce abortion in a pregnant handler. Avoid skin exposure and obtain prompt medical attention after accidental injection. Store protected from light at room temperature.