Revised: November 2009
AN: 01085/2009
Summary of Product Characteristics
1.Name of the veterinary medicinal product
OVAGENTM
2.Qualitative and quantitative composition
Each vial of OvagenTM contains the equivalent of 17.6mg NIADDK-oFSH-17.
3.Pharmaceutical form
Powder and solvent for solution for injection.
4.Pharmacological properties
Summary Presentation of the Active Ingredient:
Follicle Stimulating Hormone is a gonadotropin hormone consisting of α and ß subunits, which stimulates follicular development in females. The treatment of the female animal gives rise to an abnormally large number of follicles. As the follicles develop, oestrogen is produced, causing the release of luteinising hormone which in turn causes rupture of the follicles with ovulation. Subsequent formation of the corpora lutea leads to release of progesterone from the CL, thus elevating the circulating plasma progesterone levels above normal.
Pharmacodynamics
The mechanism of action is via specific receptors for the gonadotropins that exist only in gonadal tissues. FSH binds to the surface of small follicle granulosa cells in the ovary. The receptors for FSH are coupled to adenyl cyclase by means of guanine nucleotide-binding protein. Although the mechanism by which gonadotropins stimulate gametogenesis is not known in its entirety, it too is mediated by cyclic AMP. It is well documented in literature that an excess Luteinising Hormone (LH) will reduce ovulation rates, oocyte and embryo numbers in cows.
Pharmacokinetics
The pharmacology of FSH is well documented in readily available literature, with the pharmacokinetics showing a very rapid clearance rate from tissues. As the level of dosing is low, no untoward toxicity would be expected from the metabolic breakdown of proteins and amino acids.
The absorption of ovine FSH from the injection site is rapid. Ovine FSH is a water soluble protein complex. As such, FSH is not widely distributed, being mainly confined to the vascular compartment. FSH binds to receptors on granulosa cells at the ovary and is not retained in other tissues.
Excretion of glycoprotein hormones is by glomerular filtration, followed by degradation in the proximal renal tubule or excretion (unchanged) in the urine. The half life (t½) of ovine FSH in sheep has been estimated at approximately 2 hours. Cattle trials confirm the rapid clearance of FSH. Within 48 hours of the last injection, the concentrations of the FSH, LH and oestradiol-17ß had returned to pretreatment levels. Progesterone levels increase following superovulation, to levels approximating those of naturally pregnant cows.
Prostaglandin F2αluteolytic, leading to lysis of the corpus lutuem and luteal regression, follicle growth, oestrus and ovulation. Prostaglandin F2α is used with the product firstly to induce ovulation, and again after embryo collection, to prevent pregnancy due to embryos left behind after embryo collection.
ATC Vet Code: QG03GA90
5.Clinical particulars
5.1Target species
Cattle
5.2Indicationsfor use, specifying the target species
FSH stimulates ovarian follicle maturation and oestrogen synthesis, leading to increased ovulation rates. For use as a supplementary source of FSH to superovulate cattle programmed for embryo transfer.
5.3Contraindications
None.
5.4Undesirableeffects, frequency and seriousness
None known
5.5Specialprecautionsforuse
For treatment of healthy cattle only.
5.6Useduringpregnancyandlactation
The product can be administered to lactating and non-lactating cows. FSH residues in milk are negligible.
Not intended for use during pregnancy.
5.7Interactionwithothermedicamentsandotherformsofinteraction
As FSH is a naturally occurring substance, interactions with other drugs will be the same as endogenous follicle stimulating hormone.
5.8Posologyandmethodofadministration
Reconstitute freeze dried powder with 20ml sodium chloride diluent immediately before use.
Administer 10 - 20ml (depending on age and weight and breed of cow) intramuscularly as 8 equal injections (1.25 -2.5ml) at 12 hourly intervals over 4 days. Commence injections on Day 11 (Day 0 = Oestrus).
Administer the recommended dose of an appropriate Prostaglandin F2α on Day 13.
Cows will exhibit oestrus on Day 15. Commence insemination 12 hours after onset on oestrus and again 12 hours later.
Collect embryos on day 22 (7 days after superovulatory oestrus).
Administer the recommended dose of an appropriate Prostaglandin F2α on day 22.
The first prostaglandin is given to induce oestrus. The second prostaglandin injection administered on day 22 is to prevent the possibility of multiple pregnancy occurring as a consequence of the development of embryos left behind after flushing.
5.9Overdose
Overdosing of follicle stimulating hormone has not been recorded, due to the rapid clearance rate. Work using cultured ovine and bovine ovarian granulosa cells showed no observed adverse effects to concentrations up to 100 µg/mL. These are the cells that are sensitive to the effects of FSH, and hence their use would enhance detection of possible adverse effects. The recommended dose rate would give rise to concentrations in the animals not exceeding 3µg/mL.
5.10Specialwarningsforeachtarget species
There are no special warnings for the target species.
5.11Withdrawal periods
Meat, Milk:Zero days. Observe the recommended withdrawal period for prostaglandin used in the course of treatment.
5.12Special precautions to be taken by the person administering the product to animals
Care should be taken to avoid accidental self-injection.
When administering the prostaglandin F2α injection, read the user warnings very carefully.
6.Pharmaceutical particulars
6.1Incompatibilities
None Known.
6.2Shelf-life
2 years.
6.3Special precautions for storage
1.Store in a refrigerator (2 - 8°C)
2.Protect from light
3.The reconstituted product should be stored at 2 - 8°C; any reconstituted product remaining 24 hours after reconstitution should be discarded.
6.4Nature and contents of container
Each box contains 2 x 20ml Clear Type 1 vials, one containing ovine follicle stimulating hormone (freeze-dried powder), the other 20ml of a 0.9% w/v solution of sterile sodium chloride Ph. Eur.
6.5Special precautions for the disposal of unused product or waste materials, if any
Any unused product or waste material should be disposed of in accordance with national requirements.
7.Additional Information
Name or style and permanent address or registered place of business of the holder of the authorisation to place the product on the market:
ICPbio (UK) Ltd
Unit 4, Merlin Way
Bowerhill Industrial Estate
Melksham
Wiltshire
SN12 6TJ
UNITED KINGDOM
- marketing authorisation number:
Vm16466/4000
9.Date of last renewal
12 June 2007
10.Last Revision of the SPC
November 2009
ADDITIONAL INFORMATION
Authorised Pack Size: 2 x 20 mL vials (one containing freeze-dried FSH, the other a 0.9% w/v solution of sterile sodium chloride Ph. Eur.).