Progestin (Systemic Drug)
- Progestational drug used in horses to suppress estrus or maintain pregnancy when progestin deficient; used in swine to synchronize estrus.
- Available commercially as ReguMate® and Matrix®.
- May be used in dogs for luteal deficiency or to prevent premature delivery.
- Very sensitive to light.1
- FDA-approved for horses; off-label use in pigs and dogs.
- Extensive drug handling warnings for humans.
Altrenogest is used to suppress estrus in mares in order to facilitate induction of normal estrous cycle activity. It is also used in mares to synchronize scheduled breeding activity. In the suppression of estrous behavior in mares, this is usually related to mares that are used as performance horses.
Altrenogest is more effective in assisting in pregnancy attainment later in the transition period. Some 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 has been demonstrated to maintain pregnancy in oophorectomized mares and may be of benefit in mares that abort due to subtherapeutic progestin levels. 1
Mares will experience a predictable occurrence of estrus following drug withdrawal. In treated animals, this allows a regular cycle during the transition from winter anestrus to the physiological breeding season in mares with active ovaries. By managing the reproductive cycle, horse owners have more control over breeding procedures and the timing of the arrival of foals. In some cases, altrenogest is used for pregnancy maintenance. It is also used for reduction of aggressive behavior in stallions. 2
Altrenogest has been used in dogs for luteal insufficiency and to prevent premature delivery. 1
Altrenogest is FDA-approved for use in horses.
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.
Altrenogest acts by decreasing plasma concentrations of endogenous gonadotrophin hormones (LH and FSH). Low gonadotrophin concentrations induce the regression of large follicles (>5 mm) and do not allow the growth of follicles greater than 3 mm, leading to an absence of estrus and ovulation during treatment. The end of treatment is followed by a regular increase in LH plasma concentration allowing follicular growth and maturation. Treatment with altrenogest results in estrus (standing heat) 4-9 days after completion of the 14-day treatment period. 1
The pharmacokinetics of altrenogest have been studied in horses. After oral dosing of 44 mg/kg PO, peak levels usually occur within 15-30 minutes postadministration; 24 hours postadministration, levels were below the level of quantification. 3 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 administration. Urine levels were detectable up to 12 days postadministration. An intramuscular dose of 150 mg produced peak serum levels between 9 and 24 hours postadministration. 4 The elimination half-life was approximately 15 hours, and plasma concentrations remained above 0.5 ng/mL for 148 hours after dosing. 1
Contraindications / Precautions:
Altrenogest is contraindicated in mares having a previous or current history of uterine inflammation (ie, acute, subacute, or chronic endometritis). Natural or synthetic gestagen therapy may exacerbate existing low-grade or “smoldering” uterine inflammation into a fulminating uterine infection in some instances. When used to maintain pregnancy, it should be discontinued within 24 hours of the due date. 5 Pregnant mares with gastrointestinal diseases may not absorb altrenogest adequately, thus injectable progesterone is preferred. 6 Altrenogest should not be used in horses intended for food purposes and should not enter water courses, as this may be dangerous for fish and other aquatic organisms.
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. 7 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 may be enhanced.
The following drug interaction with altrenogest has either been reported or is theoretical in humans or animals and may be of significance in veterinary patients.
- 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.
- GRISEOFULVIN: May alter the effects of altrenogest. 1
Since it has been determined that altrenogest can disrupt the hormonal activity of other species (such as humans) via contact, it is recommended that protective gloves be worn when handling altrenogest and that a physician be contacted in the event of accidental contact. According to the available literature, altrenogest should not be handled by women of child-bearing age, and should not be administered to immature animals, animals with diabetes, uterine infection, a history of vaginal discharge or reproductive abnormalities, or animals where the owner or managers suspect they are pregnant. 2
In July of 2018, the U.S. Food and Drug Administration issued a warning alerting veterinary medical professionals and those who work with horses and pigs that altrenogest products may cause reproductive system disorders and other adverse effects in people who become exposed to the drug.
The following people should not handle altrenogest:
- Women who are or suspect that they are pregnant.
- Anyone with thrombophlebitis or thromboembolic disorders or with a history of these events.
- Anyone having cerebrovascular or coronary artery disease.
- Women with known or suspected carcinoma of the breast.
- People with known or suspected estrogen-dependent neoplasia.
- Women with undiagnosed vaginal bleeding.
- Anyone with liver dysfunction or disease.
- People with a benign or malignant tumor that developed during the use of oral contraceptives or other estrogen-containing products. 1
With regard to the FDA-issued warning that exposure to these products may cause reproductive system disorders or other adverse effects: While both men and women can be affected, the FDA cautions that teenage girls may be at risk. 1 Symptom may include abnormal or absent menstrual cycles, and some reports have described adverse effects in girls as young as 14 years of age (fda.gov).
In humans, accidental exposure to altrenogest can result in headaches, fever, abdominal pain, nausea, diarrhea, vomiting and rashes. Such exposures have occurred when personnel touched product residue on barn surfaces or equipment.
Adverse Drug Events
People handling altrenogest products should wear impermeable protective gloves. In swine and equine facilities, the outside of drug containers and syringes should be kept clean of drug residue. Such containers may be modified to enhance safety, and equine facilities are encouraged to take these precautions. Any drug that is spilled should be cleaned and decontaminated.
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). 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. Report adverse effects to your physician and poison control authorities in the event of human exposure.
Altrenogest is prohibited from use in an extra-label manner to enhance food and/or fiber production in animals.
Horses: Suppress estrus for synchronization (labeled dosage; FDA-approved) - Administer 1 ml per 110 lb body weight (0.044 mg/kg) PO every 24 hours for 15 consecutive days. 1
Prevention of abortion/pregnancy loss (all are extra-label):
a) 0.088 mg/kg PO every 24 hours.8
b) To maintain pregnancy in mares with deficient progesterone levels: 0.044 mg/kg PO every 24 hours. 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. 9
c) To maintain pregnancy in mares with placentitis: 22 – 44 mg (total dose; 10 – 20 mL) PO every 24 hours. 10
To suppress estrus (long-term) (extra-label): 0.044 mg/kg PO every 24 hours. 11
Dogs: Luteal insufficiency (extra-label) -
a) Document luteal insufficiency and rule out infectious causes of pregnancy loss. Best to avoid during first trimester. Give equine product at 2 mL per 100 lb of body weight PO every 24 hours. Monitor pregnancy with ultrasonography. Exogenous progesterone is the experimental model for pyometra in the bitch, so monitor carefully. 12
b) Luteal insufficiency, preterm labor: 0.1 mL per 10 lb body weight PO every 24 hours. 13
c) Maintain pregnancy if tocolytics (eg, terbutaline) do not control myometrial contractility: 0.088 mg/kg every 24 hours. Must be withdrawn 2-3 days before predicted whelp date. 14
Swine: To synchronize estrus in gilts that have had at least one estrous cycle (labeled dosage; FDA-approved): Follow label directions for safe use. Administer 5 ml (20 mg) per gilt for 18 consecutive days. Apply as a top-dressing on a portion of gilt’s daily feed allowance. Estrous should occur 5-6 days after completing treatment. 1
1Plumb's Veterinary Drugs.
3Machnik M, et al. Pharmacokinetics of altrenogest in horses. J Vet Phamacol Ther. 2007;30:86-90.
4McConaghy F.F., et al. Studies of the pharmacokinetic profile, in vivo efficacy and safety of injectable altrenogest for the suppression of oestrus in mares. Aust Vet J. 2016;94(7):248-255.
5Baker, T.W., Davidson A.F. Obstetrical Emergencies I. Western Veterinary Conference 2012 2012. 2012.
6Volkmann, D. Rational Use of Progestagen Therapy During Pregnancy. Western Veterinary Conference 2010 2010. 2010.
7Shideler RK, et al. The effect of altrenogest, an oral progestin, on hematologic and biochemical parameters in mares. Vet Hum Tox. 1983;25(4):250-252.
8Dascanio, J. Hormonal Control of Reproduction. Proceedings: ABVP 2009. 2009. Veterinary Information Network.
9McCue, P. Ovarian problems in the non-pregnant mare. Proceedings: Western Veterinary Conference 2003. 2003. Veterinary Information Network.
10Valla, W. Medical management of mares with complicated pregnancies. Proceedings: ACVIM Forum 2003. 2003. Veterinary Information Network.
11Squires, E.L., et al. Clinical Applications of Progestins in Mares. Comp CE. 1983;5(1):S16-S22.
12Purswell, B. Pharmaceuticals used in canine theriogenology - Part 1 & 2. Proceedings: Central Veterinary Conference 1999. 1999; Kansas City.
13Barber, J. Whelping management in the bitch. Proceedings: Western Veterinary Conference 2006. 2006. Veterinary Information Network.
14Davidson, A. Myths in small animal reproduction. Proceedings: Canine Medicine Symposium 2006. 2006. Veterinary Information Network.