OVACYST- gonadorelin injection, solution

OvaCyst by

Drug Labeling and Warnings

OvaCyst by is a Animal medication manufactured, distributed, or labeled by Bimeda, Inc., Bimeda-MTC, Polypeptide Laboratories Inc. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

SPL UNCLASSIFIED SECTION

OvaCyst®

(gonadorelin)

50 mcg/mL gonadorelin diacetate tetrahydrate

Injectable Solution

For treatment of cystic ovaries in dairy cattle. For use with cloprostenol sodium to synchronize estrous cycles to allow for fixed time artificial insemination (FTAI) in lactating dairy cows and beef cows.

CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION

DESCRIPTION

OvaCyst is a sterile solution containing 43 mcg/mL of gonadorelin (GnRH) as 50 mcg/mL gonadorelin diacetate tetrahydrate suitable for intramuscular or intravenous administration according to the indication. Gonadorelin is a decapeptide composed of the sequence of amino acids—

5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2—

a molecular weight of 1182.32 and empirical formula C55H75N17O13. The diacetate tetrahydrate ester has a molecular weight of 1374.48 and empirical formula C59H91N17O21.

Each mL OvaCyst contains:

Gonadorelin diacetate tetrahydrate

(equivalent to 43 mcg gonadorelin)….. 50 mcg

Benzyl Alcohol…………………………………… 9 mg

Sodium Chloride……………………………….. 7.47 mg

Water for Injection……………………………. q.s.

pH adjusted with potassium phosphate (monobasic and dibasic).

Gonadorelin is the hypothalamic releasing factor responsible for the release of gonadotropins (e.g., luteinizing hormone [LH], follicle stimulating hormone [FSH]) from the anterior pituitary. Synthetic gonadorelin is physiologically and chemically identical to the endogenous bovine hypothalamic releasing factor.

INDICATIONS & USAGE

INDICATIONS AND USAGE

Cystic Ovaries

OvaCyst is indicated for the treatment of ovarian follicular cysts in dairy cattle. Ovarian cysts are non-ovulated follicles with incomplete luteinization which result in nymphomania or irregular estrus. Historically, cystic ovaries have responded to an exogenous source of LH such as human chorionic gonadotropin. OvaCystinitiates release of endogenous LH to cause ovulation and luteinization.

Reproductive Synchrony

OvaCyst is indicated for use with cloprostenol sodium to synchronize estrous cycle to allow for fixed time artificial insemination (FTAI) in lactating dairy cows and beef cows.

DOSAGE & ADMINISTRATION

DOSAGE AND ADMINISTRATION

Cystic Ovaries

The intravenous or intramuscular dosage of OvaCyst is 100 mcg gonadorelin diacetate tetrahydrate (2 mL) per cow.

Reproductive Synchrony

The intramuscular dosage of OvaCyst is 100 mcg gonadorelin diacetate tetrahydrate (2 mL) per cow, used in reproductive synchrony programs similar to the following:

1. Administer the first OvaCyst injection (2 mL) at Time 0.
2. Administer the 500 mcg cloprostenol (as cloprostenol sodium) by intramuscular injection 6 to 8 days after the first OvaCyst injection.
3. Administered the second OvaCyst injection (2 mL) 30 to 72 hours after the cloprostenol sodium injection.
4. Perform FTAI 0 to 24 hours after the second OvaCyst injection, or inseminate cows on detected estrus using standard herd practices.

WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS

Not for use in humans.

Keep out of reach of children.

WITHDRAWAL PERIODS

No withdraw period or milk discard time is required when used according to the labeling.

To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Bimeda, Inc. at 1-888-524-6332. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or www.fda.gov/reportanimalae.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY

PHARMACOLOGY AND TOXICITY

Endogenous gonadorelin is synthesized and/or released from the hypothalamus during various stages of the bovine estrus cycle following appropriate neurogenic stimuli. It passes via the hypophyseal portal vessels, to the anterior pituitary to effect the release of gonadotropins (e.g. LH, FSH). Synthetic gonadorelin administered intravenously or intramuscularly also causes the release of endogenous LH or FSH from the anterior pituitary.

Gonadorelin diacetate tetrahydrate has been shown to be safe. The LD50 for mice and rats is greater than 60 mg/kg, and for dogs, greater than 600 mcg/kg, respectively. No adverse effects were noted among rats or dogs administered 120 mcg/kg/day or 72 mcg/kg/day intravenously for 15 days.

It has no adverse effects on heart rate, blood pressure, or EKG to unanesthetized dogs at 60 mcg/kg. In anesthetized dogs it did not produce depression of myocardial or system hemodynamics or adversely affect coronary oxygen supply or myocardial oxygen requirements.

The intravenous administration of 60 mcg/kg/day of gonadorelin diacetate tetrahydrate to pregnant rats and rabbits during organogenesis did not cause embryotoxic or teratogenic effects.

Further, gonadorelin diacetate tetrahydrate did not cause irritation at the site of intramuscular administration in dogs with a dose of 72 mcg/kg/day administered for seven (7) days.

TARGET ANIMAL SAFETY

In addition to the animal safety information presented in the PHARMACOLOGY AND TOXICOLOGY section, the safety of gonadorelin diacetate tetrahydrate was established through the review and evaluation of the extensive published literature available for the use of gonadorelin-containing products.

The intramuscular administration of 1000 mcg gonadorelin diacetate tetrahydrate on five (5) consecutive days to normally cycling dairy cattle had no effect on hematology or clinical chemistries.

In field studies evaluating the effectiveness of gonadorelin diacetate tetrahydrate for the treatment of ovarian follicular cysts, the incidence of health abnormalities was not significantly greater in cows administered gonadorelin diacetate tetrahydrate than cows administered a placebo injection.

The target animal safety of, and injection site reactions to, gonadorelin when used with cloprostenol sodium were evaluated during the conduct of effectiveness field studies. The incidence of health abnormalities was not significantly greater in cows administered gonadorelin than cows administered a placebo injection.

SPL UNCLASSIFIED SECTION

EFFECTIVENESS

The use of gonadorelin diacetate tetrahydrate for treatment of ovarian follicular cysts in dairy cattle was demonstrated to be effective with a treatment dose of 100 mcg gonadorelin diacetate tetrahydrate.

The effectiveness of gonadorelin for use with cloprostenol sodium to synchronize estrous cycles to allow for FTAI in lactating dairy cows was demonstrated in a field study at 10 different locations in the U.S. Four of the locations represented conditions that would typically cause heat stress in lactating cows. A total of 1607 healthy, non-pregnant, primiparous or multiparous lactating dairy cows within 40-150 days postpartum were enrolled in the study. A total of 805 cows were administered gonadorelin (1 mL; 100 mcg gonadorelin as the acetate salt) and 802 cows were administered an equivalent volume of water for injection as an intramuscular injection twice in the following regimen:

Day 0: 100 mcg gonadorelin (as the acetate salt) or sterile water for injection.

Day 7: 500 mcg cloprostenol (as cloprostenol sodium).

Day 9: 100 mcg gonadorelin (as the acetate salt) or sterile water for injection.

Fixed time AI was performed on Day 10, approximately 11-31 hours after the Day 9 injection. Cows were evaluated for pregnancy on Day 45 ± 5 days by trans-rectal ultrasound or rectal palpation. Pregnancy rate to FTAI was significantly higher (P < 0.0001) in cows treated with gonadorelin (33.4%) than the pregnancy rate to FTAI in cows treated with water (13.6%). The environmental condition (heat stress or not heat stress) did not affect the conclusion of effectiveness.

The effectiveness of gonadorelin for use with cloprostenol sodium to synchronize estrous cycles to allow for FTAI in beef cows was demonstrated in a field study at 10 different locations in the U.S. A total of 706 healthy, non-pregnant, primiparous or multiparous beef cows within 40-150 days postpartum were enrolled in the study. A total of 364 cows were administered gonadorelin (1 mL; 100 mcg gonadorelin as the acetate salt) and 342 cows were administered an equivalent volume of water for injection as an intramuscular injection twice in the following regimen:

Day 0: 100 mcg gonadorelin (as the acetate salt) or sterile water for injection

Day 7: 500 mcg cloprostenol (as cloprostenol sodium)

Day 9: 100 mcg gonadorelin (as the acetate salt) or sterile water for injection

Fixed time AI was performed immediately after the Day 9 injection. Cows were evaluated for pregnancy on Day 55 ± 5 days by trans-rectal ultrasound. Pregnancy rate to FTAI was significantly higher (P = 0.0006) in cows treated with gonadorelin (21.7%) than the pregnancy rate to FTAI in cows treated with water (7.4%).

The effectiveness of a 2-mL dose of gonadorelin diacetate tetrahydrate delivering 100 mcg gonadorelin diacetate tetrahydrate (86 mcg gonadorelin) for use with cloprostenol sodium to synchronize estrous cycles to allow for FTAI in lactating dairy cows and beef cows was also demonstrated through references to scientific literature.

HOW SUPPLIED

HOW SUPPLIED

OvaCyst is available in a concentration of 50 mcg/mL gonadorelin diacetate tetrahydrate (43 mcg/mL gonadorelin) pH adjusted with potassium phosphate (monobasic and dibasic).

OvaCyst is supplied in multi-dose vials containing 36 mL of sterile solution in a 50 mL vial.

STORAGE AND HANDLING

STORAGE, HANDLING, AND DISPOSAL

Store at controlled room temperature 20°-25°C (68°-77°F). Discard product 3 months after first use.

SPL UNCLASSIFIED SECTION

Approved by FDA under ANADA # 200-069

Manufactured for:

Bimeda, Inc.

Le Sueur, MN 56058

www.bimeda.com

PRINCIPAL DISPLAY PANEL

INGREDIENTS AND APPEARANCE

OVACYST 
gonadorelin injection, solution

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 61133-4002
Route of Administration	INTRAVENOUS, INTRAMUSCULAR

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
GONADORELIN DIACETATE TETRAHYDRATE (UNII: L8CRY8PWF2) (GONADORELIN - UNII:9O7312W37G)	GONADORELIN	50 ug  in 1 mL

Inactive Ingredients
Ingredient Name	Strength
BENZYL ALCOHOL (UNII: LKG8494WBH)	9 mg  in 1 mL
SODIUM CHLORIDE (UNII: 451W47IQ8X)	7.47 mg  in 1 mL
WATER (UNII: 059QF0KO0R)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 61133-4002-1	36 mL in 1 BOTTLE

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANADA	ANADA200069	11/08/2021

Labeler - Bimeda, Inc. (060492923)

Establishment
Name	Address	ID/FEI	Business Operations
Bimeda-MTC		256232216	manufacture

Establishment
Name	Address	ID/FEI	Business Operations
Polypeptide Laboratories Inc		962386124	api manufacture