Aglepristone (Alizin, Alizine)

By | 2013-06-07

Injectable Progesterone Blocker

Highlights Of Prescribing Information

Injectable progesterone blocker indicated for pregnancy termination in bitches; may also be of benefit in inducing parturition or in treating pyometra complex in dogs & progesterone-dependent mammary hyperplasia in cats

Not currently available in USA; marketed for use in dogs in Europe, South America, etc.

Localized injection site reactions are most commonly noted adverse effect; other adverse effects reported in >5% of patients include: anorexia (25%), excitation (23%), depression (21%), & diarrhea (13%)

What Is Aglepristone Used For?

Aglepristone is labeled (in the U.K. and elsewhere) for pregnancy termination in bitches up to 45 days after mating.

In dogs, aglepristone may prove useful in inducing parturition or treating pyometra complex (often in combination with a prostaglandin F analog such as cloprostenol).

In cats, it may be of benefit for pregnancy termination (one study documented 87% efficacy when administered at the recommended dog dose at day 25) or in treating mammary hyperplasias or pyometras.

Pharmacology/Actions

Aglepristone is a synthetic steroid that binds to the progesterone (P4) receptors thereby preventing biological effects from progesterone. It has an affinity for uterine progesterone receptors approximately three times that of progesterone. As progesterone is necessary for maintaining pregnancy, pregnancy can be terminated or parturition induced. Abortion occurs within 7 days of administration.

Benign feline mammary hyperplasias (fibroadenomatous hyperplasia; FAHs) are usually under the influence of progesterone and aglepristone can be used to medically treat this condition.

When used for treating pyometra in dogs, aglepristone can cause opening of the cervix and resumption of miometral contractility.

Within 24 hours of administration, aglepristone does not appreciably affect circulating plasma levels of progesterone, cortisol, prostaglandins or oxytocin. Plasma levels of prolactin are increased within 12 hours when used in dogs during mid-pregnancy which is probably the cause of mammary gland congestion often seen in these dogs.

Aglepristone also binds to glucocorticoid receptors but has no glucocorticoid activity; it can prevent endogenous or exogenously administered glucocorticoids from binding and acting at these sites.

Pharmacokinetics

In dogs, after injecting two doses of 10 mg/kg 24 hours apart, peak serum levels occur about 2.5 days later and mean residence time is about 6 days. The majority (90%) of the drug is excreted via the feces.

Before you take Aglepristone

Contraindications / Precautions / Warnings

Aglepristone is contraindicated in patients who have documented hypersensitivity to it and during pregnancy, unless used for pregnancy termination or inducing parturition.

Because of its antagonistic effects on glucocorticoid receptors, the drug should not be used in patients with hypoadrenocorticism or in dogs with a genetic predisposition to hypoadrenocorticism.

The manufacturer does not recommend using the product in patients in poor health, with diabetes, or with impaired hepatic or renal function as there is no data documenting its safety with these conditions.

Adverse Effects

As the product is in an oil-alcohol base, localized pain and inflammatory reactions (edema, skin thickening, ulceration, and localized lymph node enlargement) can be noted at the injection site. Resolution of pain generally occurs shortly after injection; other injection site reactions usually resolve within 2-4 weeks. The manufacturer recommends light massage of the injection site after administration. Larger dogs should not receive more than 5 mL at any one subcutaneous injection site. One source states that severe injection reactions can be avoided if the drug is administered into the scruff of the neck.

Systemic adverse effects reported from field trials include: anorexia (25%), excitation (23%), depression (21%), vomiting (2%), diarrhea (13%) and uterine infections (3.4%). Transient changes in hematologic (RBC, WBC indices) or biochemical (BUN, creatinine, chloride, potassium, sodium, liver enzymes) laboratory parameters were seen in <5% of dogs treated.

When used for pregnancy termination, a brown mucoid vaginal discharge can be seen approximately 24 hours before fetal expulsion. This discharge can persist for an additional 3-5 days. If used in bitches after the 20th day of gestation, abortion maybe accompanied with other signs associated with parturition (e.g., inappetance, restlessness, mammary congestion).

Bitches may return to estrus in as little as 45 days after pregnancy termination.

Overdosage / Acute Toxicity

When administered at 3X (30mg/kg) recommended doses, bitches demonstrated no untoward systemic effects. Localized reactions were noted at the injection site, presumably due to the larger volumes injected.

How to use Aglepristone

WARNING: As accidental injection of this product can induce abortion; it should not be administered or handled by pregnant women. Accidental injection can also cause severe pain, intense swelling and ischemic necrosis that can lead to serious sequelae, including loss of a digit. In cases of accidental injection, prompt medical attention must be sought.

Aglepristone dosage for dogs:

To terminate pregnancy (up to day 45):

a) 10 mg/kg (0.33 mL/kg) subcutaneous injection only. Repeat one time, 24 hours after the first injection. A maximum of 5 mL should be injected at any one site. Light massage of the injection site is recommended after administration. (Label information; Alizin — Virbac U.K.)

To induce parturition:

a) After day 58 of pregnancy: 15 mg/kg subcutaneously one time. 24 hours after aglepristone injection, give oxytocin 0.15 Units/kg every 2 hours until the end of parturition. ()

b) On or after day 58 of pregnancy: 15 mg/kg subcutaneously; repeat in 9 hours. In treated group, expulsion of first pup occurred between 32 and 56 hours after treatment. Use standard protocols to assist with birth (including oxytocin to assist in pup expulsion if necessary) or to intervene if parturition does not proceed. ()

As an adjunct to treating pyometra/metritis:

a) For closed cervix: 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 (10 mg/kg) once daily on days 1, 3,and 8, then follow up also on days 15 and 28 depending on the bitch’s condition. ()

b) For metritis: 10 mg/kg subcutaneously once daily on days 1,2 and 8.

For open or closed pyometra: aglepristone 10 mg/kg subcutaneously once daily on days 1,2 and 8 and cloprostenol 1 meg/ kg subcutaneously on days 3 to 7. Bitches with closed pyometra or with elevated temperature or dehydration should also receive intravenous fluids and antibiotics (e.g., amoxicillin/clavulanate at 24 mg/kg/day on days 1 – 5). If pyometra has not resolved, additional aglepristone doses should be given on days 14 and 28. ()

Aglepristone dosage for cats:

For treating mammary fibroadenomatous hyperplasia: a) 20 mg/kg aglepristone subcutaneously once weekly until resolution of signs. Cats who present with heart rates greater than 200 BPM should receive atenolol at 6.25 mg (total dose) until heart rate is less than 200 BPM with regression in size of the mammary glands. ()

Monitoring

■ Clinical efficacy

■ For pregnancy termination: ultrasound 10 days after treatment and at least 30 days after mating

■ Adverse effects (see above)

Client Information

■ Only veterinary professionals should handle and administer this product

■ When used for pregnancy termination in the bitch, clients should understand that aglepristone might only be 95% effective in terminating pregnancy when used between days 26-45

■ A brown mucoid vaginal discharge can be seen approximately 24 hours before fetal expulsion

■ Bitch may exhibit the following after treatment: lack of appetite, excitement, restlessness or depression, vomiting, or diarrhea

■ Clients should be instructed to contact veterinarian if bitch exhibits a purulent or hemorrhagic discharge after treatment or if vaginal discharge persists 3 weeks after treatment

Chemistry / Synonyms

Aglepristone is a synthetic steroid. The manufactured injectable dosage form is in a clear, yellow, oily, non-aqueous vehicle that contains arachis oil and ethanol. No additional antimicrobial agent is added to the injection.

Aglepristone may also be known as RU-534, Alizine, or Alizin.

Storage / Stability/Compatibility

Aglepristone injection should be stored below 25°C and protected from light. The manufacturer recommends using the product within 28 days of withdrawing the first dose.

Although no incompatibilities have been reported, due to the product’s oil/alcohol vehicle formulation it should not be mixed with any other medication.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Note: Not presently available or approved for use in the USA. In several countries:

Aglepristone 30 mg/mL in 5 mL and 10 mL vials; Alizine or Alizin (Virbac); (Rx)

The FDA may allow legal importation of this medication for compassionate use in animals; for more information, see the Instructions for Legally Importing Drugs for Compassionate Use in the USA found in the appendix.

Human-Labeled Products: None