SUMMARY OF PRODUCT CHARACTERISTICS

In France, Germany, Hungary, Italy, Poland, Spain and The Netherlands:

LUTEOSYL 0.075 mg/ml solution for injection for cattle and pigs.

In United Kingdom: Prellim 0.075 mg/ml solution for injection for cattle and pigs

Active substance:

d-Cloprostenol (as d-cloprostenol sodium) 0.075 mg/ml

Excipients:

Chlorocresol 1 mg/ml

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless solution, free from particles in suspension.

4. CLINICAL PARTICULARS

4.1. Target species

Cattle (cows) and pigs (sows).

Cattle (cows)

Indications for reproduction: synchronization or induction of oestrus. Induction of parturition.

Therapeutic indication:ovarian dysfunction (persistent corpus luteum, luteal cyst), interruption of pregnancy including foetal mummification, endometritis/pyometra, delayed uterine involution.

Pigs (sows)

Indications for reproduction: Induction of parturition.

4.3 Contraindications

See section 4.7

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

Do not use in animal with spastic respiratory or gastro-intestinal diseases.

4.4 Special warnings for each target species

None.

Special precautions for use in animals

To reduce the risk of anaerobic infections care should be taken to avoid injection through contaminated areas of skin. Clean and disinfect injection sites thoroughly before application.

Pigs: use only when precise date of insemination is known. Administer on day 113 of gestation, at the earliest. The veterinary medicinal product administered earlier, may impair the viability and weight of piglets.

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

d-Cloprostenol, like all F_2prostaglandins, can be absorbed through the skin and can produce bronchospasm and abortion.

Women of child-bearing age, asthmatics and persons with bronchial problems or any other type of respiratory problem must avoid any contact or use disposable plastic gloves when administering the veterinary medicinal product.

The veterinary medicinal product must be handled carefully to avoid ACCIDENTAL SELF-INJECTION OR SKIN CONTACT.

Do not eat, drink or smoke while handling the veterinary medicinal product.

In case of accidental self injection seek medical advice and show the label to the physician.

Seek medical advice immediately in case of any respiratory difficulty caused by accidental inhalation or inoculation.

In case of accidental skin contact, wash with soap and water immediately.

4.6 Adverse reactions (frequency and seriousness)

Occurrence of anaerobic infection is likely if anaerobic bacteria penetrate the tissue of the injection site. This applies especially to intramuscular injection and in particular to cows. Typical local reactions due to anaerobic infection are swelling and crepitus at the injection site.

Do not use (during the whole or part of the pregnancy) unless it is desirable to induce parturition or therapeutic interruption of pregnancy.

Do not use in animals being treated with non-steroidal anti-inflammatories, as the synthesis of endogenous prostaglandins is inhibited.

The activity of other oxytocic agents can be increased after the administration of Cloprostenol.

4.9 Amounts to be administered and administration route

For intramuscular use only:

Cattle(cows): The recommended dose is 0.150 mg d-cloprostenol/animal, equivalent to 2 ml/animal.

- Oestrus induction(also in cows with weak or silent heat): After determining the presence of corpus luteum (day 6-18 of the cycle), administer the veterinary medicinal product. Heat is generally observed in 48-60 hours. Inseminate 72-96 hours after this treatment. If heat is not observed, repeat after 11 days.

- Parturition induction: Administer the veterinary medicinal product after gestation day 270. Parturition should occur 30-60 hours post-treatment.

- Oestrus synchronisation: Administer the veterinary medicinal product twice (11 days apart). Inseminate artificially 72 and 96 hours after the second injection.

- Ovarian dysfunction: Once the presence of corpus luteum is determined, administer the veterinary medicinal product and inseminate in the first heat after the treatment. If no heat is observed, carry out a gynaecological examination again and repeat the injection 11 days after the first treatment. Insemination is 72-96 hours post-treatment.

- Endometritis or pyometra: Administer 1 dose of the veterinary medicinal product. Repeat the treatment 10-11 days later if necessary.

- Gestation interruption: Administer the veterinary medicinal product during the first half of gestation.

- Foetal mummification: Administer 1 dose of veterinary medicinal product. The foetus will be expelled after 3 or 4 days.

- Retarded uterine involution: Administer 1 dose of the veterinary medicinal product and, if indicated, repeat the treatment once or twice at 24 hour interval.

Pigs(sows):The recommended dose is 0.075 mg d-cloprostenol/animal, equivalent to 1 ml/animal.

- Parturition induction: Administer the veterinary medicinal product after day 112 of gestation. Repeat after 6 hours. Alternatively, 20 hours after the initial dose of d-cloprostenol, a myometrial stimulant (oxytocin or carazolol) may be administered. Following the protocol of double administration, in about 70% of cases, parturition occurs 20-30 hours after the first treatment.

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

In safety studies, at 10 times the therapeutic dose, no adverse reactions are reported.

As no specific antidote has been identified, in the case of overdose, symptomatic therapy is advisable.

4.11 Withdrawal period(s)

Cows: Meat and offal: 1 day.

Milk: 0 hours.

Sows: Meat and offal: 1 day.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group:Uterotonics. Prostaglandins.

ATCvet code:QG02AD90.

5.1 Pharmacodynamic properties

The veterinary medicinal product is based on dextrorotatory cloprostenol (d-Cloprostenol), a synthetic analogue of prostaglandin F_2.

d-Cloprostenol is the biologically active luteolytic component of cloprostenol and results in an approximately 3.5 fold increase in activity.

During the luteinizing stage of the oestrus cycle d-cloprostenol induces a rapid regression of the corpus luteum and a decrease in progesterone levels. The increased release of follicle stimulating hormone (FSH) allows a new follicle to mature, followed by oestrus and ovulation.

5.2 Pharmacokinetic particulars

Pharmacokinetic studies demonstrate a rapid absorption of d-cloprostenol. The peak blood level is reached a few minutes following intramuscular administration, as well as a rapid diffusion to the ovaries and uterus, the organs in which the maximum concentration is reached 10-20 minutes after administration.

Following intramuscular administration of 150 micrograms of d-cloprostenol in the cow, the peak plasma level ( C_max) of 1.4 micrograms/l is reached after approximately 90 minutes, while the elimination half life ( t_½) is in the order of 1 hour 37 minutes.

In sows, a C_maxof approximately 2 micrograms/l is observed between 30 and 80 minutes following administration of 75 micrograms d-cloprostenol, with an elimination half life in the order of 3 hours 10 minutes.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Chlorocresol

Ethanol (96%)

Citric acid monohydrate

Sodium hydroxide

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: 2 years.

Shelf life after first opening the immediate packaging: 28 days.

6.4 Special precautions for storage

Protect from light.

Avoid introduction of contamination.

6.5 Nature and composition of immediate packaging

Colourless type II glass vial with type I bromobutyl rubber stopper and aluminium cap.One glass vial of 2 ml in a cardboard box.

One glass vial of 10 ml in a cardboard box.

One glass vial of 20 ml in a cardboard box.

Five glass vials of 20 ml in a cardboard box

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused veterinary medicinal products 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

Laboratorios SYVA, S.A.U.

Avda. Párroco Pablo Díez, 49-57

24010 LEÓN - SPAIN

8. MARKETING AUTHORISATION NUMBER

Vm: 31592/4001

9. DATE OF FIRST AUTHORISATION

Date: 8 May 2009

10. DATE OF REVISION OF THE TEXT

Date: April 2014

Prohibition of sale, supply and/or use

Not applicable.

Approved: 23/04/2014