ALTRENOGEST

Chemistry - An orally administered synthetic progestational agent, altrenogest has a chemicalname of 17 alpha-Allyl-17b-hydroxyestra-4, 9, 11-trien-3-one. It may also be known as allyl trenbolone.

Storage, Stability, Compatibility

Altrenogest oral solution should be stored at room temperature.

Pharmacology - ALTRENOGEST

Progestins are primarily produced endogenously by the corpus luteum. Theytransform proliferative endometrium to secretory endometrium, enhance myometrium hypertrophyand inhibit spontaneous uterine contraction. Progestins have a dose-dependent inhibitory effect onthe secretion of pituitary gonadotropins and also have some degree of estrogenic, anabolic andandrogenic activity.
Uses, Indications - Altrenogest is indicated (labeled) to suppress estrus in mares to allow a morepredictable occurrence of estrus following withdrawal of the drug. It is used clinically to assistmares to establish normal cycles during the transitional period from anestrus to the normal breedingseason often in conjunction with an artificial photoperiod. It is more effective in assisting inpregnancy attainment later in the transition period. One group of authors (Squires et al. 1983)suggest selecting mares with considerable follicular activity (mares with one or more follicles 20mm or greater in size) for treatment during the transitional phase. Mares that have been in estrus for10 days or more and have active ovaries are also considered to be excellent candidates for progestintreatment.
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 2-5days 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 tomaintain pregnancy in oophorectomized mares and may be of benefit in mares who abort due tosub-therapeutic progestin levels.

Pharmacokinetics - ALTRENOGEST

The pharmacokinetic parameters of altrenogest were not found. Other progestin agents are rapidly metabolized by the liver.Contraindications/Precautions - The manufacturer (Regu-Mate® ¯ Hoechst) lists pregnancy asa contraindication to the use of altrenogest, however it has been used clinically to maintainpregnancy in certain mares (see Dosages below). Altrenogest should also not be used in horsesintended for food purposes.

Adverse Effects, Warnings

Adverse effects of altrenogest appear to be minimal when used at labeled dosages. One study (Shideler et al. 1983) 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 mare's with chronic uterine infections should be avoided as the infection process may be enhanced.
The manufacturer (Regu-Mate® ¯ Hoechst) 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 neoplasia

6. Women with undiagnosed vaginal bleeding

7. People with benign or malignant tumor which 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.
Overdosage - The LD50 of altrenogest in is 175-177 mg/kg in rats. No information was located regarding the effects of an accidental acute overdose in horses.

Drug Interactions

Rifampin may decrease progestin activity if administered concomitantly.
This is presumably due to microsomal enzyme induction with resultant increase in progestin metabolism. The clinical significance of this potential interaction is unknown.