Imrestor (Pegbovigrastim) – Summary of product characteristics - QL03AA90

1.NAME OF THE VETERINARY MEDICINAL PRODUCT

Imrestor 15 mg solution for injection for cattle

2.QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 2.7 ml pre-filled syringe contains:

Active substance:

Pegbovigrastim (Pegylated bovine Granulocyte Colony

Stimulating Factor [PEG bG-CSF]) 15 mg

For the full list of excipients, see section 6.1.

3.PHARMACEUTICAL FORM

Solution for injection

Clear, colourless to pale yellow solution

4.CLINICAL PARTICULARS

4.1Target species

Cattle (dairy cows and heifers).

4.2Indications for use, specifying the target species

As an aid in a herd management programme, to reduce the risk of clinical mastitis in periparturient dairy cows and heifers during the 30 days following calving.

4.3Contraindications

Do not use in case of hypersensitivity to the active substance or to any of the excipients.

4.4Special warnings for each target species

In a European field trial, the incidence of clinical mastitis observed in the treated group was 9.1 % (113/1235) and in the control group 12.4 % (152/1230), showing a relative reduction in mastitis incidence of 26.0 % (p=0.0094). The efficacy was tested together with normal management practice. Clinical mastitis is investigated as a change in the appearance of the milk or of the quarter or of both milk and quarter.

Based on all field studies, the proportion of mastitis prevented due to herd treatment with Imrestor (Prevented Fraction) is 0.25 (with 95% confidence interval 0.14 – 0.35).

The product should only be used on the basis of a positive benefit: risk assessment performed at the herd level by the responsible veterinarian.

4.5Special precautions for use

Special precautions for use in animals

Only for subcutaneous administration.

In one safety study in Jersey cows the margin of safety of this product was 1.5x the highest recommended dose (an overdose of 60µg/kg was administered on three occasions) (see also section 4.10). Do not exceed the stated dose.

As expected from the mode of action of the active substance, safety data shows that a mild and transient rise in somatic cell counts in individual cows may be seen.

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

In the case of accidental self-injection, headache and bone and muscle pain may occur. There may also be other effects including nausea and a skin rash, hypersensitivity reactions (breathing difficulties, hypotension, urticaria and angioedema). Seek medical advice immediately and show the package leaflet or the label to the physician.

People with known hypersensitivity to pegbovigrastim should avoid contact with the veterinary medicinal product.

Personal protective equipment consisting of gloves should be worn when handling broken or damaged syringes. Remove gloves and wash hands and exposed skin after use.

4.6Adverse reactions (frequency and seriousness)

In the clinical studies, non-typical anaphylactoid reactions were uncommonly observed. The cows presented with swelling of mucous membranes (notably vulva and eyelid), skin reactions, increased respiration rate and salivation. In rare cases, the animal may collapse. These clinical signs typically appear between 30 minutes and 2 hours after the first dose and resolve within 2 hours. Symptomatic treatment may be required.

Subcutaneous administration of the product may induce transient local swelling at the injection site as well as inflammatory reactions which resolve within 14 days post treatment.

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

-very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of one treatment)

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

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

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

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

4.7Use during pregnancy, lactation or lay

Can be used during pregnancy and lactation.

4.8Interaction with other medicinal products and other forms of interaction

Concurrent administration of substances which alter immune function (e.g. corticosteroids or non steroidal anti-inflammatory drugs) may reduce the efficacy of the product. Concurrent use of such products should be avoided.

No information is available on the safety and efficacy of the concurrent use of this product with vaccines.

4.9Amounts to be administered and administration route

Subcutaneous administration.

The treatment regimen consists of two syringes. The content of a single pre-filled syringe is to be injected subcutaneously to a dairy cow/heifer 7 days before the anticipated date of calving. The content of a second pre-filled syringe is to be injected subcutaneously within 24 hours after calving. The intervals between the two administrations should not be less than 3 days or more than 17 days.

A single syringe delivers a dose of 20-40 µg/kg pegbovigrastim for most cows depending on bodyweight: e.g. a dose of 21 µg/kg bodyweight for a 700 kg cow or 33 µg/kg bodyweight for a 450 kg heifer.

Excessive shaking of the syringe may aggregate pegbovigrastim, reducing its biological activity. The solution should be visually inspected prior to use. Only clear solutions without particles should be used.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

Evidence from similar active substances in humans suggests that accidental administration of more than the authorised dose could result in adverse reactions, which are related to the activity of pegbovigrastim.

Treatment should be symptomatic. There is no known antidote.

In one safety study in Jersey cows, at overdose of 60 µg/kg, administered on three occasions (1.5x the highest recommended dose), abomasal ulcers were observed.

4.11 Withdrawal period(s)

Meat and offal: zero days.

Milk: zero days.

5.PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Colony stimulating factors.

ATCvet code: QL03AA90

5.1Pharmacodynamic properties

Pegbovigrastim is a modified form of the naturally occurring immunoregulatory cytokine, bovine granulocyte colony stimulating factor (bG-CSF). Bovine granulocyte colony stimulating factor is a naturally occurring protein produced by mononuclear leukocytes, endothelial cells and fibroblasts. Colony stimulating factors regulate the production and functional activities of immune cells. The immunoregulatory activities of granulocyte colony stimulating factor concerns notably cells of the neutrophilic granulocyte lineage which bear cell surface receptors for the protein. The product increases the number of circulating neutrophils. It has also been proved that it enhances myeloperoxidase hydrogen peroxide halide mediated microbiocidal capabilities of neutrophils. bG-CSF presents additional functions beyond its action on neutrophils and these may be direct or indirect functions on other cells/receptors and cytokine pathways.

No information is available with regard to a possible immune reaction towards the product or towards the endogenous molecule (bG-CSF) after repeated use of the product in cows.

5.2Pharmacokinetic particulars

There is no information available about the pharmacokinetics of pegbovigrastim in cattle.

6.PHARMACEUTICAL PARTICULARS

6.1List of excipients

Citric acid monohydrate.

Arginine hydrochloride.

Arginine.

Water for injections.

6.2Incompatibilities

Do not mix with any other veterinary medicinal products.

6.3Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale: 2 years. Shelf -life after first opening the immediate packaging: use immediately.

6.4Special precautions for storage

Store in a refrigerator (2 C – 8 C).

Do not freeze.

Sensitive to light. Store in original packaging.

The product may be stored at 25 °C for 24 hours maximum.

6.5Nature and composition of immediate packaging

2.7 ml of solution for injection in a pre-filled polypropylene colourless syringe with siliconised chlorobutyl stopper and a stainless steel needle with needle guard.

The syringes are packed into cardboard boxes as follows;

10 syringes.

50 syringes.

100 syringes.

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

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

7.MARKETING AUTHORISATION HOLDER

Eli Lilly and Company Limited

Elanco Animal Health

Priestley Road

Basingstoke

Hampshire RG24 9NL

United Kingdom

8.MARKETING AUTHORISATION NUMBER(S)

EU/2/15/193/001-003

9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 09/12/2015

10.DATE OF REVISION OF THE TEXT

Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency (http://www.ema.europa.eu/).