SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Hypophysin LA 35 µg/ml solution for injection for cattle and pigs

Depotocin 35 µg/ml solution for injection for cattle and pigs (AT/DE)

Hypophysin LA 35 microgram/ml solution for injection for cattle and pigs (IE/UK)

Hypophysin 35 µg/ml solution for injection for cattle and pigs (EE)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml contains:

Active substance:

Carbetocin 35.00 µg

Excipients:

Chlorocresol 1.00 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless solution.

4. CLINICAL PARTICULARS

4.1 Target species

Cattle, pig

4.2 Indications for use, specifying the target species

Cow:

- Uterine atony during the puerperal period

- Placental retention as a consequence of uterine atony

- Initiation of milk ejection in stress-induced agalactia or in conditions requiring udder emptying

Sow:

-Acceleration or restart of parturition after disruption of uterine contractions (uterine atony or inertia)

following the expulsion of at least 1 piglet

- Supportive therapy of mastitis-metritis-agalactia (MMA-) syndrome

- Initiation of milk ejection

- Shortening of total parturition duration as a component of synchronisation of parturition in sows. The product may be applied to sows which have previously been administered an appropriate PGF_2(e.g. cloprostenol) not prior to day 114 of pregnancy and have not started farrowing within 24 hours after the PGF_2injection (day 1 of pregnancy is the last day of insemination)

4.3 Contraindications

Do not administer to accelerate parturition if cervix is not opened or if there is a mechanical cause for the delayed parturition such as physical obstruction, positional and postural abnormalities, convulsive labour, threatened rupture of uterus, uterine torsion, relative foetal oversize or deformities of the birth canal.

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

4.4 Special warnings for each target species

The responsiveness to carbetocin of the myometrium is likely to be close to zero from the 5^thto the 11^thday post partum. Therefore, the administration of the veterinary medicinal product during this period is likely to be inefficient and should be avoided.

If treatment with carbetocin should fail, then it is advisable to reconsider the aetiology of the condition, specifically if hypocalcaemia could be a complicating factor.

In case of severe septic metritis, appropriate concomitant therapy should be instigated when administering the veterinary medicinal product.

4.5 Special precautions for use

Special precautions for use in animals

The interval between two injections should not be shorter than 24 hours.

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

In case of an accidental self-injection of the veterinary medicinal product in non-pregnant women the following effects may occur: facial flushing and warmth, lower abdominal pain. These effects usually disappear within a short span of time.

Pregnant women, women post partum and breast-feeding women should not use this product, in order to avoid an accidental exposure. In case of accidental self-injection uterine contractions could be induced in pregnant women.

In the case of accidental self-injection, seek medical advice and show the package leaflet to the doctor.

In case of accidental contact with the skin, the corresponding area should be thoroughly cleaned with soap and water, as carbetocin may be absorbed through the skin.

In case of contact with the eyes, they should be thoroughly rinsed with water.

Persons with a known hypersensitivity to carbetocin or any of the excipients should not administer the product.

Women of childbearing age should administer the product with special caution.

4.6 Adverse reactions (frequency and seriousness)

Carbetocin may have a uterotonic effect in the late pregnancy.

4.7 Use during pregnancy, lactation or lay

The veterinary medicinal product is indicated to induce milk ejection.

See also 4.3 Contraindications.

4.8 Interaction with other medicinal products and other forms of interaction

The administration of oxytocin after the administration of the veterinary medicinal product is un-necessary. Due to a possible intensification of the effect of oxytocin, undesirable uterine spasms may be induced.

4.9 Amounts to be administered and administration route

For intramuscular or intravenous use. The product is in general only administered once.

Cows

For all indications:

6.0 – 10.0 ml/animal, corresponding to 210 – 350 µg carbetocin/animal

Sows

For shortening of total parturition duration as a part of the synchronisation of

parturition:

1.0 ml/animal, corresponding to 35 µg carbetocin/animal

For acceleration or restart of parturition after disruption of uterine contractions (uterine atony or inertia) following the expulsion of at least 1 piglet:

1.0 - 2.0 ml/animal, corresponding to 35 - 70 µg carbetocin/animal

For MMA and milk ejection:

3.0 – 6.0 ml/animal, corresponding to 105 – 210 µg carbetocin/animal

The dosage requirements can be variable within the indicated limits based on the assessment of the veterinarian.

In case of treatment for milk ejection in the cow and sow or supportive therapy in MMA-syndrome in sow, a repeated administration is possible after 1 to 2 days.

The rubber stopper of the vial may be safely punctured up to 25 times. Otherwise, automatic syringe equipment, or a suitable draw-off needle, should be used for the 50 and 100 ml vials to avoid excessive puncturing of the closure.

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

An overdosing of more than 400 µg of carbetocin/animal could increase the stillbirth rate in older sows if administered during prolonged parturition.

An overdosing of 600 µg of carbetocin/animal may induce profuse lactation in sows that may result in diarrhoea, reduced weight gain and increased mortality in their piglets.

Carbetocin is considered as moderately irritant. At the injection sites of treated animals, focal lymphocytic infiltration was observed at higher doses (1000 µg of carbetocin/animal).

4.11 Withdrawal periods

Cattle, pig Meat and offal: Zero days

Cattle Milk: Zero hours

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Systemic hormonal preparations, excl. sex hormones and insulin

ATCvet code: QH01BB03

5.1 Pharmacodynamic properties

Carbetocin is a synthetic analogue of the posterior pituitary lobe hormone oxytocin and has its physiological and pharmacological main effects at the smooth muscle (induction and increase of contractions) of reproductive organs.

Carbetocin has the same effect as natural oxytocin: at the oestrogen stimulated uterus it causes a change from weak, spontaneous and irregular to synchronised, regular, increased and directed contractions. Moreover, in the mammary gland it produces physiological contractions of the myoepithelial cells in the alveolae and small lactiferous ducts as well as a simultaneous relaxation of the teat sphincter.

The action of carbetocin is prolonged and it causes an intensification of the physiological effect.

5.2 Pharmacokinetic particulars

Carbetocin is, due to its strongly developed peptidase-resistance, much more slowly degraded in vivo and distinguishes itself by a prolonged efficacy. Carbetocin is much more lipophilic than exogenously applied oxytocin and therefore, a better distribution and a longer effect on the receptors occur. Beside the stability against proteases, this may also contribute to the prolonged increase of uterine tone activity. After administration of 600 µg of carbetocin, in sows a bicompartimental kinetic was observed. The elimination half-life is approximately 85 - 100 min. There are no essential differences between intramuscular and intravenous administration.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Chlorocresol

Acetic acid (glacial)

Sodium acetate trihydrate

Sodium hydroxide (for pH adjustment)

Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

6.3 Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale:

3 years

Shelf-life after first opening the immediate packaging:

28 days

6.4. Special precautions for storage

Store in a refrigerator (2 - 8 °C). Keep the vial in the outer carton in order to protect from light.

6.5 Nature and composition of immediate packaging

Colourless glass injection vial, type I, containing 10 ml, 20 ml, 50 ml or 100 ml, respectively, solution for injection closed with a fluorinated bromobutyl rubber stopper and sealed with an aluminium cap.

1 x 10 ml, 1 x 20 ml, 1 x 50 ml, 12 x 50 ml, 1 x 100 or 12 x 100 ml solution for injection, packaged in an outer cardboard box.

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 products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Veyx-Pharma GmbH

Söhreweg 6

34639 Schwarzenborn

Germany

8. MARKETING AUTHORISATION NUMBER

Vm 27569/4003

9. DATE OF FIRST AUTHORISATION

05 August 2014

10. DATE OF REVISION OF THE TEXT

August 2014

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

APPROVED 5/08/14