Fixplan 200 IU/ml Lyophilisate and Solvent for Solution for Injection

Composition

Lyophilisate vial contains:

Active substance

Gonadotrophin, equine serum 5000 IU

Excipients:

For the full list of excipients, see section 6.1.

Solvent vial contains 25 ml

Excipients:

For the full list of excipients, see section 6.1.

Each ml of the reconstituted solution contains:

Active substance:

Gonadotrophin, equine serum 200 IU

Excipients:

For the full list of excipients, see section 6.1.

6.1 List of excipients

Lyophilisate:

Mannitol

Disodium phosphate

Sodium dihydrogen phosphate dihydrate

Solvent:

Disodium phosphate dihydrate

Sodium dihydrogen phosphate dihydrate

Water for injections

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Pharmaceutical form

Lyophilisate and solvent for solution for injection.

Lyophilisate: white powder

Solvent: clear colourless solution

Reconstituted solution: clear colourless solution free from visible particles.

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Pharmacological properties

Pharmacotherapeutic group: Genito urinary system and sex hormones, gonadotropins and other ovulation stimulants, serum gonadotrophin.

ATC vet code: QG03GA03

5.1 Pharmacodynamic properties

Equine serum gonadotropin is a complex glycoprotein obtained from the serum of pregnant mares. This substance is capable of supplementing and being substituted for follicle stimulating gonadotrophin of the anterior pituitary gland in both female and male animals.

Equine serum gonadotropin is a potent gonadotrophin with dual FSH and LH activity. It is composed of two non-covalently associated alpha and beta subunits and is heavily glycosylated on its CTP tail. This extensive glycosylation is of key importance in obtaining the extended half-life in blood that is typical of equine serum gonadotropin. As equine serum gonadotropin binds to FSH and LH receptors, it stimulates follicular growth and follicular maturation in the days preceding oestrus and ovulation. Limited amounts of equine serum gonadotropin will result in induction and synchronisation of ovulation in cattle and small ruminants, irrespective of their cyclicity prior to treatment. Administration of slightly higher amounts will modestly increase ovulation rate and litter size. Administration of high amounts of equine serum gonadotropin will result in superovulation, therefore resulting in the numerous blastocysts needed for embryo transfer.

5.2 Pharmacokinetic particulars

The pharmacokinetic profile observed following injection of equine serum gonadotropin is characterised by the very long half-life generated by the glycosylation (N and O glycosylation) of the equine serum gonadotropin molecule. It also explains why a single equine serum gonadotropin administration has the ability to support follicular growth throughout the full duration of the follicular phase (2 to 5 days depending on the species).

Absorption of equine serum gonadotropin is rapid. In all three species studied, equine serum gonadotropin is rapidly absorbed from the injection site and Cmax is reached within 8 hours (pig/sheep) or 16 hours (cattle) following injection. Bioavailability following intramuscular injection (compared to intravenous administration) is high in all species (cattle: 72 %; pigs: 71.3 %; sheep: 92.6 %). Equine serum gonadotropin elimination is slow. The elimination half-life has been shown to range between 34 and 150 hours depending on the species.

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Target species

Cattle, sheep and pigs.

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Indications

To stimulate the development of the ovarian follicle in the female.

Cows: Treatment of anoestrus/ induction of oestrus, induction of superovulation and increase in fertility rates after progestagen pre-treatment.

Ewes: Increase in fertility rates after progestagen pre-treatment.

Sows: Treatment of anoestrus post-weaning/ induction of oestrus.

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Dosage

Routes of administration: Cattle and sheep: intramuscular use; pigs: intramuscular or subcutaneous use.

Reconstitution: Reconstitute the lyophilisate with the solvent provided. Dissolve the lyophilisate with a small quantity of solvent. Mix to obtain a homogenous solution. Transfer this solution into the vial that contains the rest of the solvent and mix until completely dissolved.

Ensure the lyophilisate has fully dissolved before use.

Use normal aseptic precautions. Avoid the introduction of contamination.

Anoestrus is often caused by inadequate management (feeding and housing). Improvement of management is therefore a prerequisite for a successful treatment.

Equine serum gonadotropin is a protein hormone which acts on the ovary to stimulate the production of follicles. The number of follicles produced can be influenced by the dose of equine serum gonadotropin administered and this must be taken into account when, for instance, calculating the dose for a particular flock of ewes in which oestrus synchronisation is desired. In general, the further out of season that breeding is attempted and the lower the normal prolificacy of the flock, the more equine serum gonadotropin that will be required.

An average dose of 500 IU / ewe is recommended as a useful starting point but doses ranging from 400 - 750 IU have been used on occasion. It is therefore recommended that accurate flock records are kept of breed, dose given, time of injection and lambs produced so that in future seasons the amount can, if necessary, be adjusted for optimum results.

Superovulation in cattle

The veterinary medicinal product may be used for the superovulation of female donor cattle prior to embryo transfer.

The following is an example, of a regime that has been successfully been applied in the field:

• A single dose of the veterinary medicinal product (1,500 - 3,000 IU) is injected between day 8 and 13 of a normal oestrus cycle. NB: the exact dose of the veterinary medicinal product required to achieve effective superovulation will depend upon a number of factors particularly the breed, age, reproductive history, general health and nutritional status of the donor female and is subject to individual variation.

• 48 hours after injection of the veterinary medicinal product, luteolysis is inducedby the injection of a prostaglandin analogue. Usually 1 ½ times the normal luteolytic dose is administered. Oestrus normally occurs approximately 48 hours after the prostaglandin injection.

• Insemination is carried out at 60 and 72 hours after prostaglandin injection.

• Collection of fertilised embryos (flushing) is carried out 6-8 days after insemination. Suitable embryos are transferred to female recipient cattle whose oestrus cycles have previously been synchronised with that of the donor female. Experience has shown that oestrus cycles in donor and recipient females should be synchronised within ± 24 hours if reasonable success is to be expected.

• A further prostaglandin treatment (usually 1 ½ times the luteolytic dose) should be administered at the time of embryo collection.

Note:

1. Despite the application of a suitable treatment regime certain individual donor cows may fail to respond.

2. Wide variations in response may be expected between individual animals. Repeated treatment of a single animal may also yield variable results.

3. The overall success of an embryo transfer protocol will be influenced by the availability of suitable equipment and the skill and experience of the operator.

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Contraindications

None.

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Adverse reactions

In rare cases, as with all protein preparations, anaphylactic reactions may occur shortly after injection (See Section 4.5).

The frequency of adverse reactions is defined using the following convention:

- very common (more than 1 in 10 animals treated displaying adverse reaction(s))

- common (more than 1 but less than 10 animals in 100 animals treated)

- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

- rare (more than 1 but less than 10 animals in 10,000 animals treated)

- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

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Warnings

Special precautions for use in animals

In case of anaphylactic shock, symptomatic treatment (e.g. adrenaline or corticosteroids) should be administered.

Where the possibility of multiple ovulations has not been excluded by clinical examination following administration of the veterinary medicinal product to uniparous species (unless to induce superovulation in cattle), it is inadvisable to permit service or to inseminate animals during the first heat produced.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

Studies in laboratory animals exhibited teratogenic effects after the administration of eCG. Pregnant women, those intending to become pregnant, or whose pregnancy status is unknown, should not handle the product.

The veterinary medicinal product can influence fertility in humans after injection. Administer the veterinary medicinal product with caution to avoid self-injection. In case of accidental self-injection, seek medical advice immediately and show the package leaflet or label to the physician.

Accidental spillage on the skin should be washed immediately with soap and water.

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Use during pregnancy, lactation or lay

Do not use during pregnancy.

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Interactions

None known.

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Overdose

No specific treatment or antidote is recommended.

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Special warnings

Especially in sheep, dosing of eCG should be adapted to the breed (doses should be lower in prolific breeds) and to the breeding season of animals (higher when used off season).

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Withdrawal period

Cattle

Meat and offal: Zero days

Milk: Zero hours

Sheep

Meat and offal: Zero days

Milk: Zero hours

Pigs

Meat and offal: Zero days

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Incompatibilities

Do not mix with any other veterinary medicinal product, except solvent supplied for use with the veterinary medicinal product.

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Immediate packaging

Lyophilisate: 8 ml colourless type I glass vial closed with a grey bromobutyl rubber stopper, aluminium seals and prolypropylene caps.

Solvent: 30 ml colourless type IIglass vial closed with a grey bromobutyl rubber stopper, aluminium seals and polypropylene caps.

Carton box containing 1 vial of 5,000 IU lyophilisate and 1 vial of solvent (25 ml).

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Storage

Store in a refrigerator (2°C – 8°C).

Keep the vials in the outer carton in order to protect from light.

The reconstituted solution should be stored in the refrigerator (2°C - 8°C).

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

Shelf life after reconstitution according to directions: 24 hours.

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Disposal of unused product

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

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Additional information

Vm 54400/4001

9 DATE OF FIRST AUTHORISATION

03 March 2021

10 DATE OF REVISION OF THE TEXT

March 2025

Approved: 12 March 2025

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Registration holder

Syn Vet-Pharma Ireland Limited

G24A Arclabs Research & Innovation Centre

Carriganore

Waterford X91 XD96

Ireland

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