domperidone

For prevention of fescue toxicosis in periparturient mares.

Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian. For oral use in horses only. Horses with hypersensitivity to domperidone should not receive EQUIDONE Gel. All foals born to mares treated with EQUIDONE Gel should be tested for serum IgG concentrations. Do not use for horses intended for human consumption.

Equidone® Gel

For prevention of fescue toxicosis in periparturient mares.

EQUIDONE® Gel (domperidone)

For use as a spawning aid in finfish broodstock.

Domperidone is a D2 dopamine receptor antagonist that blocks the agonistic action of fescue alkaloids at the cellular level. Unlike other D2 antagonist drugs, domperidone does not readily cross the blood-brain barrier4. Distribution studies with radio-labeled drug in animals have shown wide tissue distribution, but low brain concentration. Small amounts of the drug cross the placenta in rats5. In humans, domperidone is 91-93% bound to plasma proteins. Domperidone in humans undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation1. Urinary and fecal excretions of domperidone in humans amount to 31 and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged in humans is small (10% of fecal excretion and approximately 1% of urinary excretion). The average terminal plasma half-life of domperidone administered orally to horses is approximately 6 hours with very low systemic bioavailability.

EQUIDONE® Gel (domperidone)

Horses with hypersensitivity to domperidone should not receive EQUIDONE Gel.

EQUIDONE® Gel (domperidone)

Not for use in humans. Keep out of the reach of children. May damage fertility. Pregnant women should exercise caution because exposure may damage the unborn child. Use in a well-ventilated area. Wear gloves, goggles, and suitable protective clothing. Care should be taken to avoid accidental contact or self-injection. In the event of accidental self-injection, seek medical advice immediately. INHALATION: May be harmful. If breathing becomes difficult, move to fresh air, and contact a physician. INGESTION: May be harmful. If the person is conscious, wash out mouth with copious amounts of water. Contact a physician. EYE CONTACT: May be harmful. In case of contact, flush with copious amounts of water for at least 15 minutes. Assure adequate flushing by separating eyelids with fingers. Contact a physician. SKIN CONTACT: May be harmful. In case of contact, flush with copious amounts of water for at least 15 minutes. Remove contaminated clothing and wash before re-using. Contact a physician. OTHER HEALTH INFORMATION: The toxicological properties of sGnRHa have not been thoroughly investigated. The actions are similar to luteinizing hormone releasing hormone (LHRH, Gonadotropin releasing hormone, GnRH) in humans. LHRH is the key mediator in the liberation of the pituitary gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). LHRH may modify reproductive ability by influencing plasma gonadotropin levels and concomitantly gonadal steroid levels. To obtain a product Safety Data Sheet, call Syndel at (888) 384-7431

WARNING: Care should be taken to avoid accidental contact or self-injection. In the event of accidental self-injection, seek medical advice immediately. Use in a well ventilated area. Wear gloves, goggles and suitable protective clothing. Not for use in humans. Keep out of the reach of children. INHALATION: May be harmful. If breathing becomes difficult, move to fresh air, and contact a physician. INGESTION: May be harmful. If the person is conscious, wash out mouth with copious amounts of water. Contact a physician. EYE CONTACT: May be harmful. In case of contact, flush with copious amounts of water for at least 15 minutes. Assure adequate flushing by separating eyelids with fingers. Contact a physician. SKIN CONTACT: May be harmful. In case of contact, flush with copious amounts of water for at least 15 minutes. Remove contaminated clothing and wash before re-using. Contact a physician. OTHER HEALTH INFORMATION: The toxicological properties of sGnRHa have not been thoroughly investigated. The actions are similar to luteinizing hormone releasing hormone (LHRH, Gonadotropin releasing hormone, GnRH) in humans. LHRH is the key mediator in the liberation of the pituitary gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). LHRH may modify reproductive ability by influencing plasma gonadotropin levels and concomitantly gonadal steroid levels. To obtain a product Safety Data Sheet, call Syndel at sales@syndel.com

Ovaprim® Injectable Solution (Salmon Gonadotropin Releasing Hormone Analog 20 µg/ml + Domperidone 10 mg/ml)For intraperitoneal or intramuscular injection

Not for use in humans. For oral use in animals only. Keep this and all drugs out of the reach of children. Pregnant and lactating women should use caution when handling EQUIDONE Gel, as systemic exposure to domperidone may affect reproductive hormones. Domperidone is not approved for any indication in humans in the US. The safety of domperidone in lactating women and their nursing children has not been evaluated. Consult a physician in case of accidental human exposure.

EQUIDONE® Gel (domperidone)

Failure of passive transfer of immunoglobulins (IgG) may occur when using EQUIDONE Gel even in the absence of leakage of colostrum or milk. All foals born to mares treated with EQUIDONE Gel should be tested for serum IgG concentrations. Do not use in horses intended for human consumption.

EQUIDONE® Gel (domperidone)

The most common adverse reactions associated with treatment with EQUIDONE Gel are premature lactation (dripping of milk prior to foaling) and failure of passive transfer. In a laboratory effectiveness study with 32 periparturient mares (17 treated with EQUIDONE Gel and 15 treated with vehicle control) 3/17 (18%) mares treated with EQUIDONE Gel experienced premature lactation. In the 25 foals (16 foals of mares treated with EQUIDONE Gel and 9 foals of vehicle control mares) evaluated for passive transfer, failure of passive transfer occurred in 13/16 (81%) foals of mares treated with EQUIDONE Gel and 8/9 (89%) foals of control mares. Failure of passive transfer in foals of mares treated with EQUIDONE Gel was not solely due to physical loss of colostrum through premature lactation, because 77% of EQUIDONE Gel treated mares that did not drip milk prior to foaling had foals with failure of passive transfer. In a field study with 279 periparturient mares treated with EQUIDONE Gel, premature lactation was reported in 3 mares (1%) and failure of passive transfer was reported in 3 foals (1%). In two additional field studies, a total of 2,556 mares were treated with EQUIDONE Gel or a bioequivalent formulation for 2,730 breeding seasons. Horses in these studies were treated with EQUIDONE Gel for varying durations. Of the 2,730 breeding seasons evaluated, premature lactation was reported in 262 mares (9.6%), failure of passive transfer was reported in 50 foals (1.8%), and premature parturition (gestation length ≤320 days) occurred in 13 mares (<0.5%). To report suspected adverse events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Dechra at (866) 933-2472. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or online at http://www.fda.gov/reportanimalae

EQUIDONE® Gel (domperidone)

Orally administer 0.5 mg/lb (1.1 mg/kg) once daily starting 10 to 15 days prior to Expected Foaling Date (EFD). Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk after foaling.

Oral

Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian. For oral use in horses only. Horses with hypersensitivity to domperidone should not receive EQUIDONE Gel. All foals born to mares treated with EQUIDONE Gel should be tested for serum IgG concentrations. Do not use for horses intended for human consumption.

Equidone® Gel

DIRECTIONS FOR USE: Ovaprim® is packaged ready for use in liquid form. Precise amounts for individual injections should be withdrawn directly from the bottle into a syringe. Due to the viscosity of the product, use of syringes with Luer Lock tips or permanently attached needles is strongly recommended. Use of syringes with slip tips is not recommended since needles could inadvertently eject under pressure. CLEANLINESS: Syringes/needles should be sterile prior to use. LOADING: Withdraw only enough solution from the bottle of Ovaprim® Injectable Solution as will be required for the weight of the fish. With the needle pointed upward and directed away from your face, squeeze the syringe gently to expel any trapped air. INJECTION: Hold the fish firmly and insert the needle into the abdominal cavity/belly between the pelvic fin and the vent or into the muscle on either side of the dorsal fin. For intra-abdominal injection in smaller species, it may be helpful to secure the fish on a soft wet surface such as a sponge, and to place the fish on its side and inject into the rear abdominal cavity to avoid contact with internal organs. Inject Ovaprim® carefully. After injection, gently place the fish into a container of clean aerated water. SEDATION FOR HANDLING AND RECOVERY: If necessary, sedate broodstock prior to Ovaprim® injection. DOSE: A general dose of Ovaprim® is 0.5 ml per kilogram of bodyweight. This dose may vary among finfish species and physiological state of individual animals. Environment and temperature also play a significant role in the reproductive process and may affect dose and timing. For most species, only a single dose of Ovaprim® is required; but treatment of fish with a single dose of Ovaprim® is only effective in fish that are within or near their natural spawning season. For other species, a split dose may be needed. For split dosing, a loading dose of 10% of the total dose should be injected, followed by injection of the remaining 90% of the total dose at least 6 hours later. In warm water species, ovulation may occur in as little as 4 hours post treatment, so fish should be monitored accordingly. Signs of ovulation/spermiation may include a noticeable swelling and “softening” of the abdomen; presence of eggs in the water; the ability to easily express eggs from the female and milt from males; and when sexes are held together in the same tank, onset of spawning behavior (e.g., males “chasing” females). However, it is important to note that the interval between treatment and the onset of ovulation is variable between species and temperature, and treated fish should be disturbed as little as possible to reduce stress during final maturation. Males may respond in shorter periods of time than females of the same species. DOSE CALCULATION: The dose is calculated based on the weight of the fish. FISH WEIGHT x OVAPRIM® DOSAGE = AMOUNT OF INJECTION Examples: 1) 0.2 kg 0.5 ml/kg 0.1 ml 2) 50 gm 0.5 µl/gm 25 µl Use of a needle guard to limit the penetration of the needle into the fish may be helpful, and use of a tuberculin or similar syringe is also recommended for accurate dosing in small fish and to minimize trauma at the injection site. Intramuscular injection may result in bleeding at the injection site. Swelling, ulceration, whiteness, redness, or hypopigmentation may also be observed at the injection site.

INTRAPERITONEAL, INTRAMUSCULAR

Ovaprim® Injectable Solution (Salmon Gonadotropin Releasing Hormone Analog 20 µg/ml + Domperidone 10 mg/ml)For intraperitoneal or intramuscular injection

Ovaprim® is packaged ready for use in liquid form. Precise amounts for individual injections should be withdrawn directly from the bottle into a syringe. Due to the viscosity of the product, use of syringes with Luer Lock tips or permanently attached needles is strongly recommended. Use of syringes with slip tips is not recommended since needles could inadvertently eject under pressure. Use of a needle guard to limit the penetration of the needle into the fish may be helpful. For small fish, use of a tuberculin or similar syringe is also recommended for accurate dosing and to minimize trauma at the injection site. CLEANLINESS: Syringes and needles should be sterile prior to use. LOADING: Withdraw only enough solution from the bottle of Ovaprim® as will be required for the weight of the fish. With the needle pointed upward and directed away from your face, squeeze the syringe gently to expel any trapped air. INJECTION: Hold the fish firmly and insert the needle into the abdominal cavity/belly between the pelvic fin and the vent or into the muscle on either side of the dorsal fin. For intra-abdominal injection in smaller species, it may be helpful to secure the fish on a soft wet surface such as a sponge, and to place the fish on its side and inject into the rear abdominal cavity to avoid contact with internal organs. Inject Ovaprim® carefully. After injection, gently place the fish into a container of clean aerated water. Intramuscular injections may result in bleeding at the injection site. Swelling, ulceration, whiteness, redness, or hypopigmentation may also be observed at the injection site. SEDATION FOR HANDLING AND RECOVERY: If necessary, sedate finfish broodstock prior to Ovaprim® injection. DOSE: A general dose of Ovaprim® is 0.5 ml per kilogram of bodyweight. This dose may vary among finfish species and physiological state of individual animals. Environment and temperature also play a significant role in the reproductive process and may affect dose and timing. For most species, only a single dose of Ovaprim® is required; but treatment of fish with a single dose of Ovaprim® is only effective in fish that are within or near their natural spawning season. For some species, a split dose may be needed. For split dosing, a loading dose of 10% of the total dose should be injected, followed by injection of the remaining 90% of the total dose at least 6 hours later. In warm water species, ovulation may occur in as little as 4 hours post treatment, so fish should be monitored accordingly. Signs of ovulation/spermiation may include a noticeable swelling and “softening” of the abdomen; presence of eggs in the water; the ability to easily express eggs from the female and milt from males; and when sexes are held together in the same tank, onset of spawning behavior (e.g., males “chasing” females). However, it is important to note that the interval between treatment and the onset of ovulation is variable between species and temperature, and treated fish should be disturbed as little as possible to reduce stress during final maturation. Males may respond in shorter periods of time than females of the same species. DOSE CALCULATION: The dose is calculated based on the weight of the fish. FISH WEIGHT x OVAPRIM® DOSAGE = AMOUNT OF INJECTION Examples: 1) 0.2 kg 0.5 ml/kg 0.1 ml 2) 50 gm 0.5 µl/gm 25 µl

INTRAPERITONEAL, INTRAMUSCULAR

Determine the appropriate dose for the body weight of the mare based on the dosing table below. One cc will treat 220 lb (100 kg) of body weight. Table 1. Dosing Table Weight (lb) Weight (kg) cc Domperidone (mg) 550-660 250-300 3 330 661-880 301-400 4 440 881-1100 401-500 5 550 1101-1320 501-600 6 660 Turn the dial ring until the edge of the ring nearest the tip of the syringe lines up with the dose to be delivered. Remove the syringe cap. Make sure the horse's mouth is free of food or other obstructions. Insert the nozzle of the syringe through the interdental space of the horse's mouth and deposit the gel on the back of the tongue by depressing the plunger. Recap the syringe. This is a 25 cc multi-dose syringe. Please note that for subsequent doses, it will be necessary to adjust for previous doses. For example, if the intended dose for a horse is 5 cc, then the dial ring is set at 5 cc for the first dose, at 10 cc for the second dose, at 15 cc for the third dose, at 20 cc for the fourth dose, and at 25 cc for the fifth dose.

ORAL

EQUIDONE® Gel (domperidone)

Orally administer 0.5 mg/lb (1.1 mg/kg) once daily starting 10 to 15 days prior to Expected Foaling Date (EFD). Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk after foaling.

ORAL

EQUIDONE® Gel (domperidone)