Aglepristone
Aglepristone is a synthetic steroid acting as a **progesterone receptor antagonist**. It is primarily used in veterinary medicine for **pregnancy termination** in dogs and cats, as well as the medical management of **pyometra** and feline **fibroadenomatous mammary hyperplasia**. Because it is formulated in an oil-alcohol base, localized injection site reactions are common. **Clinical Pearl**: As a competitive antagonist, aglepristone does not decrease circulating endogenous progesterone levels; rather, it blocks progesterone's biological action directly at the receptor level.
Mechanism: Aglepristone competitively binds to **progesterone (P4) receptors** in the uterus and other target tissues. * In dogs, its affinity for uterine progesterone receptors is ~3x that of endogenous progesterone; in queens, it is ~9x greater. * **Pathway**: Aglepristone binding โ blockade of progesterone signaling โ withdrawal of pregnancy support โ cervical dilation and resumption of myometrial contractility โ fetal resorption or abortion (usually within 7 days). * It also binds to **glucocorticoid receptors** acting as an antagonist, which can block endogenous or exogenously administered glucocorticoids from acting at these sites.
Dosing by species
- To terminate pregnancy (up to day 45) ยท 10 mg/kg (0.33 mL/kg) subcutaneous injection only. Repeat one time, 24 hours after the first injection. ยท SC ยท q24h ยท 2 doses ยท A maximum of 5 mL should be injected at any one site. Light massage of the injection site is recommended.
- To induce parturition ยท At day 60 (post-estimated LH surge): 15 mg/kg SC and another dose 24 hours later. Subsequently, give oxytocin 0.15 Units/kg SC at hourly intervals until last pup is delivered. ยท SC ยท q24h ยท 2 doses ยท Additional studies confirming efficacy and safety are warranted before routine clinical application.
- To induce parturition ยท On or after day 58 of pregnancy: 15 mg/kg subcutaneously; repeat in 9 hours. ยท SC ยท Repeat in 9 hours ยท 2 doses ยท Expulsion of first pup occurred between 32 and 56 hours after treatment. Use standard protocols to assist with birth.
- As an adjunct to treating pyometra/metritis (preserve fertility) ยท Treatment begun at week 2-4 of diestrus with a single SC injection of aglepristone at 10 mg/kg. Doses are repeated at days 2, 7, and 14. ยท SC ยท Days 1, 2, 7, 14 ยท 14 days ยท During first 7 days, daily injections of amoxicillin/clavulanic acid were also given.
- For closed cervix pyometra ยท 6 mg/kg twice daily on the first day followed by the same dose once daily on days 2, 3, and 4. Some prefer using larger doses (10mg/kg) once daily on days 1, 3, and 8, then follow up also on days 15 and 28 depending on the bitch's condition. ยท SC ยท Variable ยท Variable
- For metritis ยท 10 mg/kg subcutaneously once daily on days 1, 2 and 8. ยท SC ยท Days 1, 2, 8 ยท 8 days
- For open or closed pyometra ยท aglepristone 10 mg/kg subcutaneously once daily on days 1, 2 and 8 and cloprostenol 1 microgram/kg subcutaneously on days 3 to 7. ยท SC ยท Days 1, 2, 8 ยท 8 days ยท Bitches with closed pyometra or with elevated temperature/dehydration should also receive IV fluids and antibiotics. If unresolved, additional doses on days 14 and 28.
Routes of administration
Contraindications
- Known hypersensitivity to aglepristone
- Pregnancy (unless used specifically for pregnancy termination or inducing parturition)
- Hypoadrenocorticism (Addison's disease) or genetic predisposition to it
- Peritonitis (must be ruled out before using for pyometra)
- Caution in patients with poor health, diabetes, or impaired hepatic/renal function
Adverse effects
- Injection site reactions (pain, edema, skin thickening, ulceration, localized lymph node enlargement)
- Anorexia (25%)
- Excitation (23%)
- Depression (21%)
- Diarrhea (13%)
- Uterine infections (3.4%)
- Vomiting (2%)
- Brown mucoid vaginal discharge (associated with pregnancy termination)
- Mammary gland congestion
Drug interactions
- Progestins (natural or synthetic) ยท Could reduce the efficacy of aglepristone
- Glucocorticoids ยท Aglepristone could reduce the efficacy of glucocorticoid treatment due to receptor antagonism ยท moderate
- Ketoconazole ยท May interact with aglepristone (manufacturer warning, likely due to CYP450 enzyme inhibition)
- Itraconazole ยท May interact with aglepristone (manufacturer warning)
- Erythromycin ยท May interact with aglepristone (manufacturer warning)
Monitoring
- Clinical efficacy
- For pregnancy termination: ultrasound 10 days after treatment and at least 30 days after mating
- Injection site reactions (pain, swelling, ulceration)
- Systemic adverse effects (anorexia, excitation, depression, diarrhea)
Overdose
When administered at 3X (30 mg/kg) recommended doses, bitches demonstrated no untoward systemic effects. Localized reactions were noted at the injection site, presumably due to the larger volumes injected.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.