Imrestor (Pegbovigrastim) – Package leaflet - QL03AA90

PACKAGE LEAFLET FOR

Imrestor 15 mg solution for injection for cattle

1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE, IF DIFFERENT

Marketing authorisation holder:

Eli Lilly and Company Limited

Elanco Animal Health

Priestley Road

Basingstoke

Hampshire

RG24 9NL

United Kingdom

Manufacturer for the batch release:

Eli Lilly and Company Limited

Speke Operations

Fleming Road

Liverpool

L24 9LN

United Kingdom

2.NAME OF THE VETERINARY MEDICINAL PRODUCT

Imrestor 15 mg solution for injection for cattle pegbovigrastim

3.STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

The product is a clear, colourless to pale yellow solution for injection containing 15 mg pegbovigrastim (pegylated bovine colony stimulating factor) in a pre-filled syringe.

4.INDICATION(S)

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.

5.CONTRAINDICATIONS

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

6.ADVERSE REACTIONS

During the clinical field studies, non typical anaphylactoid type 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)

If you notice any serious effects or other effects not mentioned in this package leaflet, please inform your veterinary surgeon.

7.TARGET SPECIES

Cattle (dairy cows and heifers).

8.DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION

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.

9.ADVICE ON CORRECT ADMINISTRATION

Only for subcutaneous injection.

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.

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

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). 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.

10.WITHDRAWAL PERIOD

Meat and offal: zero days.

Milk: zero days.

11.SPECIAL STORAGE PRECAUTIONS

Keep out of sight and reach of children.

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.

Do not use this veterinary medicinal product after the expiry date which is stated on the carton and on the pre-filled syringe.

12.SPECIAL WARNING(S)

In animals, which have pharmaceutically altered immune function e.g. those which have recently received systemically administered corticosteroids or non-steroidal anti-inflammatory drugs the product may not be effective. Concurrent use of such products should be avoided.

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

Evidence from similar active substances in humans suggests that accidental administration to cattle 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.

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

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

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

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

Pregnancy and lactation:

Can be used in pregnancy and lactation

Incompatibilities:

Do not mix with other veterinary medicinal products.

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.

13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY

Medicines should not be disposed of via wastewater or household waste.

Ask your veterinary surgeon or pharmacist how to dispose of medicines no longer required. These measures should help to protect the environment.

14.DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED

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

15.OTHER INFORMATION

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

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.

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 alongside normal dairy herd management practices. During this EU study, 312 cows were treated with Imrestor for every 10 cases of clinical mastitis that were prevented during the periparturient period.

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).

Available in boxes of 10, 50 or 100 syringes.

Not all pack sizes may be marketed.

For any information about this veterinary medicinal product, please contact the local representative of the marketing authorisation holder.

België/Belgique/Belgien (Belgium)

Lietuva (Lithuania)

Eli Lilly Benelux NV./S.A.

Eli Lilly Regional Operations GmbH

Division Elanco Animal Health

Elanco Animal Health

Markiesstraat 1

Kölblgasse 8-10

B-1000 Brussels

A-1030 Viena Austrija

Belgium

 

Česká republika (Czech Republic)

Luxembourg/Luxemburg

Eli Lilly Regional Operations GmbH

Eli Lilly Benelux NV./S.A.

Elanco Animal Health

Division Elanco Animal Health

Kölblgasse 8-10

Markiesstraat 1B-1000 Brussels

A-1030 Vídeň

Belgium

Austria

 

Hrvatska (Croatia)

Magyarország (Hungary)

Eli Lilly Regional Operations GmbH

Eli Lilly Regional Operations GmbH

Elanco Animal Health

Elanco Animal Health

Kölblgasse 8-10

Kölblgasse 8-10

A-1030 Beč

A-1030 Bécs

Austria

Austria

Danmark (Denmark)

Malta

Elanco Animal Health A/SLyskær 3 E, 2 t.v.

Eli Lilly Regional Operations GmbH

2730 Herlev

Elanco Animal Health

Denmark

Kölblgasse 8-10

 

A-1030 Wien

 

L-Awstrija

Deutschland (Germany)

Nederland (the Netherlands)

Lilly Deutschland GmbH

Eli Lilly Nederland B.V.

Abteilung Elanco Animal Health

Elanco Animal Health

Papendorpseweg 83

61352 Bad Homburg

3528 BJ UTRECHT

Germany

The Netherlands

Eesti (Estonia)

Norge (Norway)

Eli Lilly Regional Operations GmbH

Elanco Animal Health A/S

Elanco Animal Health

Lyskær 3 E, 2 t.v.

Kölblgasse 8-10

2730 Herlev

A-1030 Viini

Denmark

Austria

 

España (Spain)

Österreich (Austria)

Lilly S.A.

Eli Lilly Regional Operations GmbH

Elanco Valquimica S.A.

Elanco Animal Health

Avda. de la Industria, 30

Kölblgasse 8-10

E-28108 Alcobendas Madrid

A-1030 Wien

Spain

Austria

Ελλάδα (Greece)

Eli Lilly Regional Operations GmbH Elanco Animal Health

Kölblgasse 8-10 A-1030 Wien Austria

Suomi (Finland)

Elanco Animal Health A/S Lyskær 3 E, 2 t.v.

2730 Herlev Denmark

France (France)

Lilly France

Elanco Animal Health

24 Boulevard Vital Bouhot

92200 Neuilly sur Seine France

Ireland (Ireland)

Eli Lilly & Company Ltd.

Elanco Animal Health

Priestley Road

Basingstoke RG24 9NL

United Kingdom

Ísland (Iceland)

Elanco Animal Health A/SLyskær 3 E, 2 t.v. 2730 Herlev

Denmark

Italia (Italy)

Eli Lilly Italia S.p.A

Elanco Animal Health

Via Gramsci, 731-733

SestoFiorentino

-50019 Firenze

Italy

Κύπρος (Cyprus)

Eli Lilly Regional Operations GmbH Elanco Animal Health

Kölblgasse 8-10 A-1030 Wien Austria

Latvija (Latvia)

Eli Lilly Regional Operations GmbH

Elanco Animal Health

Kölblgasse 8-10

A-1030 Vīne

Austria

Република България (Bulgaria)

Eli Lilly Regional Operations GmbH Elanco Animal Health

Kölblgasse 8-10

A-1030 Виена Австрия

Polska (Poland)

Eli Lilly Polska Sp. z o.o. ul. Żwirki I Wigury 18A 02 – 092 Warszawa Polska

Portugal (Portugal)

Lilly Farma – Produtos Farmacêuticos, Lda

Elanco Animal Health

Torre Ocidente, Rua Galileu Galilei

piso 7 fração A/D

1500-392 Lisboa

Portugal

România (Romania)

Eli Lilly Romania SRL Str. Menuetului nr. 12

Cladirea D, et 2, 013713, sector 1 Bucuresti

România

Slovenská Republika (Slovak Republic)

Eli Lilly Regional Operations GmbH

Elanco Animal Health

Kölblgasse 8-10

A-1030 Viedeň

Austria

Slovenija (Slovenia)

Eli Lilly Regional Operations GmbH

Elanco Animal Health

Kölblgasse 8-10

A-1030 Wien

Austria

Sverige (Sweden)

Elanco Animal Health A/S Lyskær 3 E, 2 t.v.

2730 Herlev Denmark

United Kingdom

Eli Lilly and Company Ltd

Elanco Animal Health

Priestley Road

Basingstoke RG24 9NL

United Kingdom

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