Altren Solution 0.22% (1000 mL)

ALTREN for suppression of estrus in mares. Suppression of estrus allows for a predictable occurrence of estrus following drug withdrawal in mares with ovarian follicles 20 mm or greater. Suppression of estrus will facilitate.

Key Benefits

• Attainment of regular cyclicity during the transition from winter anestrus to the physiological breeding season.
• Management of prolonged estrus conditions.
• Scheduled breeding during the physiological breeding season.

Indications

Altren (altrenogest) Solution 0.22% is indicated to suppress estrus in mares. Suppression of estrus allows for a predictable occurrence ofestrus following drug withdrawal. This facilitates the attainment of regular cyclicity during the transition from winter anestrus to thephysiological breeding season. Suppression of estrus will also facilitate management of prolonged estrus conditions. Suppression of estrus maybe used to facilitate scheduled breeding during the physiological breeding season.

View Altren Drug Facts Sheet.

While wearing protective gloves, remove shipping cap and seal; replace with enclosed plastic dispensing cap. Remove cover from bottledispensing tip and connect luer lock syringe (without needle). Draw out appropriate volume of Altren solution. (Note: Do not remove syringewhile bottle is inverted as spillage may result.) Detach syringe and administer solution orally at the rate of 1 mL per 110 pounds of body weight(0.044 mg/kg) once daily for 15 consecutive days. Administer solution directly on the base of the mare's tongue or on the mare's usual grainration. Replace cover on bottle dispensing tip to prevent leakage. Excessive use of a syringe may cause the syringe to stick; therefore, replacesyringe as necessary.

Which Mares will respond to Altren (altrenogest) Solution 0.22%:

Extensive clinical trials have demonstrated that estrus will be suppressed in approximately 95% of the mares within three days; however, thepost-treatment response depended on the level of ovarian activity when treatment was initiated. Estrus in mares exhibiting regular estrus cyclesduring the breeding season will be suppressed during treatment; these mares return to estrus four to five days following treatment and continueto cycle normally. Mares in winter anestrus with small follicles continued in anestrus and failed to exhibit normal estrus following withdrawal.

Response in mares in the transition phase between winter anestrus and the summer breeding season depended on the degree of follicularactivity. Mares with inactive ovaries and small follicles failed to respond with normal cycles post-treatment, whereas a higher proportion ofmares with ovarian follicles 20 mm or greater in diameter exhibited normal estrus cycles post-treatment. Altren (altrenogest) Solution 0.22%was very effective for suppressing the prolonged estrus behavior frequently observed in mares during the transition period (February, Marchand April). In addition, a high proportion of these mares responded with regular estrus cycles post-treatment.

Specific Uses for Altren (altrenogest) Solution 0.22%:

Suppression of Estrus To:

1. Facilitate attainment of regular cycles during the transition period from winter anestrus to the physiological breeding season. To facilitateattainment of regular cycles during the transition phase, mares should be examined to determine the degree of ovarian activity. Estrus in mareswith inactive ovaries (no follicles greater than 20 mm in diameter) will be suppressed but these mares may not begin regular cycles followingtreatment. However, mares with active ovaries (follicles greater than 20 mm in diameter) frequently respond with regular post-treatment estruscycles.
2. Facilitate management of the mare exhibiting prolonged estrus during the transition period. Estrus will be suppressed in mares exhibitingprolonged behavioral estrus either early or late during the transition period. Again, the post-treatment response depends on the level of ovarianactivity. The mares with greater ovarian activity initiate regular cycles and conceive sooner than the inactive mares. Altren (altrenogest)Solution 0.22% may be administered early in the transition period to suppress estrus in mares with inactive ovaries to aid in the management ofthese mares or to mares later in the transition period with active ovaries to prepare and schedule the mare for breeding.
3. Permit scheduled breeding of mares during the physiological breeding season. To permit scheduled breeding, mares which are regularlycycling or which have active ovarian function should be given Altren (altrenogest) Solution 0.22% daily for 15 consecutive days beginning 20days before the date of the planned estrus. Ovulation will occur 5 to 7 days following the onset of estrus as expected for non-treated mares.Breeding should follow usual procedures for mares in estrus. Mares may be regulated and scheduled either individually or in groups.

Additional Information:

A 3-year well controlled reproductive safety study was conducted in 27 pregnant mares, and compared with 24 untreated control mares. Treatedmares received 2 mL altrenogest solution 0.22%/110 lb body weight (2x dosage recommended for estrus suppression) from day 20 to day 325of gestation. This study provided the following data:

1. In filly offspring (all ages) of treated mares, clitoral size was increased.
2. Filly offspring from treated mares had shorter interval from Feb. 1 to first ovulation than fillies from their untreated mare counterparts.
3. There were no significant differences in reproductive performance between treated and untreated animals (mares & their respectiveoffspring) measuring the following parameters:
• interval from Feb. 1 to first ovulation, in mares only.
• mean interovulatory interval from first to second cycle and second to third cycle, mares only.
• follicle size, mares only.
• at 50 days gestation, pregnancy rate in treated mares was 81.8% (9/11) and untreated mares was 100% (4/4).
• after 3 cycles, 11/12 treated mares were pregnant (91.7%) and 4/4 untreated mares were pregnant (100%).
• colt offspring of treated and control mares reached puberty at approximately the same age (82 & 84 weeks respectively).
• stallion offspring from treated and control mares showed no differences in seminal volume, spermatozoal concentration, spermatozoalmotility, and total sperm per ejaculate.
• stallion offspring from treated and control mares showed no difference in sexual behavior.
• testicular characteristics (scrotal width, testis weight, parenchymal weight, epididymal weight and height, testicular height, width & length)were the same between stallion offspring of treated and control mares.

Warning:

For oral use in horses only. Keep this and all other medications out of the reach of children. Do not use in horses intended for humanconsumption.

Human Warnings:

Skin contact must be avoided as Altren (altrenogest) Solution 0.22% is readily absorbed through unbroken skin. Protective glovesmust be worn by all persons handling this product. Pregnant women or women who suspect they are pregnant should not handleAltren (altrenogest) Solution 0.22%. Women of childbearing age should exercise extreme caution when handling this product.Accidental absorption could lead to a disruption of the menstrual cycle or prolongation of pregnancy. Direct contact with the skinshould therefore be avoided. Accidental spillage on the skin should be washed off immediately with soap and water.

Information For Handlers:

Warning: Altren (altrenogest) Solution 0.22% is readily absorbed by the skin. Skin contact must be avoided; protective gloves mustbe worn when handling this product.

Effects of Overexposure

There has been no human use of this specific product. The information contained in this section is extrapolated from data available on otherproducts of the same pharmacological class that have been used in humans. Effects anticipated are due to the progestational activity ofaltrenogest.

Acute effects after a single exposure are possible; however, continued daily exposure has the potential for more untoward effects such asdisruption of the menstrual cycle, uterine or abdominal cramping, increased or decreased uterine bleeding, prolongation of pregnancy andheadaches. The oil base may also cause complications if swallowed.

In addition, the list of people who should not handle this product (see below) is based upon the known effects of progestins used in humans on achronic basis.

People who should not handle this product:

1. Women who are or suspect they are pregnant.
2. Anyone with thrombophlebitis or thromboembolic disorders or with a history of these events.
3. Anyone with cerebral-vascular 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 tumors which developed during the use of oral contraceptives or other estrogen-containing products.
8. Anyone with liver dysfunction or disease.

Accidental Exposure

Altrenogest is readily absorbed from contact with the skin. In addition, this oil based product can penetrate porous gloves. Altrenogest shouldnot penetrate intact rubber or impervious gloves; however, if there is leakage (i.e., pinhole, spillage, etc.), the contaminated area covered bysuch occlusive materials may have increased absorption. The following measures are recommended in case of accidental exposure.

Skin Exposure: Wash immediately with soap and water.

Eye Exposure: Immediately flush with plenty of water for 15 minutes. Get medical attention.

If Swallowed: Do not induce vomiting. Altren (altrenogest) Solution 0.22% contains an oil. Call a physician. Vomiting should be supervisedby a physician because of possible pulmonary damage via aspiration of the oil base. If possible, bring the container and labeling to thephysician.

Storage:

Store at or below 25°C (77°F). Reclose tightly.