Altrenogest (Regu-Mate, Matrix)

By | 2013-06-08

Oral Progestin

Highlights Of Prescribing Information

Progestational drug used in horses to suppress estrus or maintain pregnancy when progestin deficient; used in swine to synchronize estrus

May be used in dogs for luteal deficiency or as a treatment to prevent premature delivery

Many “handling” warnings for humans (see below)

Very sensitive to light

What Is Altrenogest Used For?

Altrenogest (Regu-Mate) is indicated (labeled) to suppress estrus in mares to allow a more predictable occurrence of estrus following withdrawal of the drug. It is used clinically to assist mares to establish normal cycles during the transitional period from anestrus to the normal breeding season often in conjunction with an artificial photoperiod. It is more effective in assisting in pregnancy attainment later in the transition period. Some authors () suggest selecting mares with considerable follicular activity (mares with one or more follicles 20 mm or greater in size) for treatment during the transitional phase. Mares that have been in estrus for 10 days or more and have active ovaries are also considered excellent candidates for progestin treatment.

Altrenogest is effective in normally cycling mares for minimizing the necessity for estrus detection, for the synchronization of estrus, and permitting scheduled breeding. Estrus will ensue 2-5 days after treatment is completed and most mares ovulate between 8-15 days after withdrawal. Altrenogest is also effective in suppressing estrus expression in show mares or mares to be raced. Although the drug is labeled as contraindicated during pregnancy, it has been demonstrated to maintain pregnancy in oophorectomized mares and may be of benefit in mares that abort due to sub-therapeutic progestin levels.

The product Matrix is labeled for synchronization of estrus in sexually mature gilts that have had at least one estrous cycle. Treatment with altrenogest results in estrus (standing heat) 4-9 days after completion of the 14-day treatment period.

Altrenogest has been used in dogs for luteal insufficiency and as a treatment to prevent premature delivery.

Pharmacology/Actions

Progestins are primarily produced endogenously by the corpus luteum. They transform proliferative endometrium to secretory endometrium, enhance myometrium hypertrophy and inhibit spontaneous uterine contraction. Progestins have a dose-dependent inhibitory effect on the secretion of pituitary gonadotropins and have some degree of estrogenic, anabolic and androgenic activity.

Pharmacokinetics

In horses, the pharmacokinetics of altrenogest have been studied (). After oral dosing of 44 mg/kg PO, peak levels usually occur within 15-30 minutes post-dose; 24 hours post-dose, levels were below the level of quantification. Elimination half-lives are approximately 2.5-4 hours. Altrenogest appears to be primarily eliminated in the urine. Peak urine levels occur 3-6 hours after oral dosing. Urine levels were detectable up to 12 days post-administration.

Before you take Altrenogest

Contraindications / Precautions / Warnings

The manufacturer (Regu-Mate — Intervet) lists pregnancy as a contraindication to the use of altrenogest, however it has been used clinically to maintain pregnancy in certain mares (see Dosages below). Altrenogest should also not be used in horses intended for food purposes.

Adverse Effects

Adverse effects of altrenogest appear to be minimal when used at labeled dosages. One study () found negligible changes in hematologic and most “standard” laboratory tests after administering altrenogest to 4 groups of horses (3 dosages, 1 control) over 86 days. Occasionally, slight changes in Ca++, K+, alkaline phosphatase and AST were noted in the treatment group, but values were only slightly elevated and only noted sporadically. No pattern or definite changes could be attributed to altrenogest. No outward adverse effects were noted in the treatment group during the trial.

Use of progestational agents in mares with chronic uterine infections should be avoided as the infection process maybe enhanced.

Overdosage / Acute Toxicity

The LD50 of altrenogest is 175-177 mg/kg in rats. No information was located regarding the effects of an accidental acute overdose in horses or other species.

How to use Altrenogest

Altrenogest dosage for dogs:

For luteal insufficiency:

a) Document luteal insufficiency and rule out infectious causes of pregnancy loss. Best to avoid during first trimester. Give equine product (Regumate) at 2 mL per 100 lbs of body weight PO once daily. Monitor pregnancy with ultrasound. Remember that exogenous progesterone is the experimental model for pyometra in the bitch, so monitor carefully. ()

b) For luteal insufficiency, pre-term labor: 0.1 mL per 10 lb body weight PO once daily. ()

c) To maintain pregnancy if tocolytics (e.g., terbutaline) do not control myometrial contractility: 0.088 mg/kg once daily (q24h). Must be withdrawn 2-3 days prior to predicted whelp date. ()

Altrenogest dosage for horses:

To suppress estrus for synchronization:

a) Administer 1 mL per 110 pounds body weight (0.044 mg/ kg) PO once daily for 15 consecutive days. May administer directly on tongue using a dose syringe or on the usual grain ration. (Package insert; Regu-Mate — Intervet)

b) 0.044 mg/kg PO for 8-12 days ()

To maintain pregnancy in mares with deficient progesterone levels:

a) 22-44 mg daily PO ()

b) 0.044 mg/kg PO once daily. Three options for treatment: 1) treatment until day 60 of pregnancy or greater AND measurement of endogenous progesterone level of >4 ng/mL; 2) treatment until day 120 of pregnancy; or 3) treatment until end of pregnancy. ()

To maintain pregnancy in mares with placentitis: a) 10-20 mL (22-44 mg) daily PO () To suppress estrus (long-term): a) 0.044 mg/kg PO daily ()

Altrenogest dosage for swine:

For synchronization of estrous in sexually mature gilts that have had at least one estrous cycle:

a) Follow label directions for safe use. Administer 6.8 mL (15 mg) per gilt for 14 consecutive days. Apply as a top-dressing on a portion of gilt’s daily feed allowance. Estrous should occur 4-9 days after completing treatment. (Package insert; Matrix — Intervet)

Client Information

■ The manufacturer (Regu-Mate, Matrix — Intervet) lists the following people as those who should not handle the product:

1. Women who are or suspect that they are pregnant

2. Anyone with thrombophlebitis or thromboembolic disorders or with a history of these events

3. Anyone having cerebrovascular or coronary artery disease

4. Women with known or suspected carcinoma of the breast

5. People with known or suspected estrogen-dependent neoplasias

6. Women with undiagnosed vaginal bleeding

7. People with benign or malignant tumor that developed during the use of oral contraceptives or other estrogen containing products

■ Altrenogest can be absorbed after skin contact and absorption can be enhanced if the drug is covered by occlusive materials (e.g., under latex gloves, etc.). If exposed to the skin, wash off immediately with soap and water. If the eyes are exposed, flush with water for 15 minutes and get medical attention. If the product is swallowed, do not induce vomiting and contact a physician or poison control center.

■ This medication is prohibited from use in an extra-label manner to enhance food and/or fiber production in animals

Chemistry / Synonyms

An orally administered synthetic progestational agent, altrenogest has a chemical name of 17 alpha-Allyl- 17beta-hydroxyestra-4,9,11-trien-3-one.

Altrenogest may also be known as: allyl trenbolone, A-35957, A-41300, RH-2267, or RU-2267, Regu-Mate, or Matrix.

Storage / Stability

Altrenogest oral solution should be stored at room temperature. Altrenogest is extremely sensitive to light; dispense in light-resistant containers.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Altrenogest 0.22% (2.2 mg/mL) in oil solution in 150 mL and 1000 mL bottles; Regu-Mate (Intervet); (Rx). Approved for use in horses not intended for food. This medication is banned in racing animals in some countries.

Altrenogest 0.22% (2.2 mg/mL) in 1000 mL bottles; Matrix (Intervet); (OTC, but extra-label use prohibited). Approved for use in sexually mature gilts that have had at least one estrous cycle. Gilts must not be slaughtered for human consumption for 21 days after the last treatment. The FDA prohibits the extra-label use of this medication to enhance food and/or fiber production in animals.

Human-Labeled Products: None