SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Tylucyl 200 mg/ml solution for injectionfor cattle and pigs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml contains:

Active ingredient(s):

Tylosin .. 200 000 IU(equivalent to approximately 200 mg)

Excipient(s):

Benzyl alcohol (E1519).......................................................................................... 40 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection

Pale yellow to amber coloured solution.

4. CLINICAL PARTICULARS

4.1 Target species

Cattle, pigs

4.2 Indications for use, specifying the target species

For the treatment of specific infections conditions (stated below) caused by microorganisms susceptible to tylosin.

Cattle (adult):

-Respiratory infections, metritis caused by Gram-positive microorganisms, mastitis caused by Streptococcus spp, Staphylococcus sppor Mycoplasma sppand interdigital necrobacillosis, i.e. panaritium or foot root.

Calves:

-Respiratory infections and necrobacillosis.

Pigs(more than 25 kg):

-Enzootic pneumonia, haemorrhagic enteritis, erysipelas and metritis.

-Arthritis caused by Mycoplasma spp. and Staphylococcus spp.

For information regarding swine dysentery see section 4.5.

4.3 Contraindications

Do not administer to horses.

Intramuscular injection can be fatal in chickens and turkeys.

Do not administer to animals with known hyper-sensitivity to tylosin, other macrolides or to any of the excipients.

4.4 Special warnings for each target species

None

4.5 Special precautions for use

Special precautions for use in animals

Due to likely variability (time, geographical) in susceptibility of bacteria to tylosin, bacteriological sampling and susceptibility testing are recommended.

Official, national and regional antimicrobial policies should be taken into account when the product is used.

Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to tylosin and may decrease the effectiveness of treatment with other macrolide antibiotics due to the potential for cross resistance.

A high rate of in vitro resistance has been demonstrated in European strains of Brachyspira hyodysenteriae implying that the product will not be sufficiently efficacious against swine dysentery.

Where repeat injections are to be administered, use different sites for each injection.

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

Care should be taken to avoid accidental self-injection.

In case of accidental self- injection, seek medical advice immediately and show the package leaflet or the label to the physician.

In the event of accidental skin contact, wash thoroughly with soap and water. In case of accidental eye contact, flush the eyes with plenty of clean, running water.

Wash hands after use.

Tylosin may induce irritation. Macrolides, such as tylosin, may also cause hypersensitivity (allergy) following injection, inhalation, ingestion or contact with skin or eye. Hypersensitivity to tylosin may lead to cross reactions to other macrolides and vice versa.

Allergic reactions to these substances may occasionally be serious and therefore direct contact should be avoided.

Do not handle the product if you are allergic to ingredients in the product.

If you develop symptoms following exposure, such as skin rash, you should seek medical advice and show the physician this warning. Swelling of the face, lips and eyes or difficulty in breathing are more serious symptoms and require urgent medical attention.

4.6 Adverse reactions (frequency and seriousness)

Hypersensivity reactions may occur.

Blemishes may occur at the site of injection and can persist for up to 21 days following administration.

In very rare cases the following have been observed:

-Swelling/inflammation at the site of injection

-Vulval swelling in cattle,

-Oedema of the rectal mucosa, partial anal protrusion (rosebudding), erythema and

pruritus in pigs.

-Anaphylactic shock and death.

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 1,00 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).

4.7 Use during pregnancy, lactation or lay

Studies in laboratory animals have neither produced any evidence of a teratogenic or foetotoxic effects nor consequences on animals’ fertility.

The safety of the veterinary medicinal product has not been established during

pregnancy and lactationin the target species.

Use only according to the benefit/risk assessment by the responsible veterinarian.

4.8 Interaction with other medicinal products and other forms of interaction

None known.

4.9 Amounts to be administered and administration route

For Intramuscular or slow intravenous (only in cattle) injection.

Cattle:

5 mg to 10 mg of tylosin per kg bodyweight per day during 3 days, i.e 2.5 to 5 ml of solution per 100 kg bodyweight.

Maximum injection volume per injection site should not exceed 15 ml.

Pigs (more than 25 kg):

5 mg to 10 mg of tylosin per kg bodyweight per day during 3 days, i.e 2.5 to 5 ml of solution per 100 kg bodyweight.

To ensure a correct dosage, body weight should be determined as accurately as possible to avoid underdosing.

The closures should not be broached more than 15 times. In order to prevent excessive broaching of the stopper, a suitable multiple dosing device should be used.

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

In pigs and calves an intramuscular injection of 30 mg/kg per day during 5 consecutive days produced no adverse effects.

4.11 Withdrawal period(s)

Cattle:

Meat and offal: 28 days

Milk: 108 hours

Pigs:

Meat and offal: 14 days

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antibacterials for systemic use, macrolides, tylosin

ATCvet code: QJ01FA90

5.1 Pharmacodynamic properties

Tylosin is a macrolide antibiotic with a pKa of 7.1. Tylosin is structurally similar to erythromycin. It is produced by Streptomyces fradiae. Tylosin has a low solublility in water.

Tylosin exerts its antibiotic activity by a similar mechanism to other macrolides, i.e. by binding the 50 S fraction of the ribosomes resulting, in an inhibition of the synthesis of proteins. Tylosin has mainly a bacteriostatic activity.

Tylosin has an antibiotic effect against Gram positive cocci (Staphylococci, Streptococci), Gram positive bacilli (Arcanobacterium spp., Clostridium spp., Erysipelothrix, Actinomyces), some Gram-negative bacilli (Haemophilus spp., Pasteurella spp., Mannheimia spp.) and Mycoplasma.

Resistance to macrolides is usually plasmid-mediated but modification of ribosomes may occur through chromosomal mutation. Resistance can occur by i) decreased entry into bacteria (most common with the gram-negative bacteria), ii) synthesis of bacterial enzymes that hydrolyze the drug and, iii) modification of the target (the ribosome).

This latter resistance type may also lead to cross-resistance with other antibiotics that preferentially bind to bacterial ribosome. Gram-negative anaerobic bacteria are often resistant.

5.2 Pharmacokinetic particulars

Absorption:

Following intramuscular injection the tylosin concentration reaches its maximum at 3-4 hours following administration.

Distribution, Biotransformation and Elimination:

The maximum concentration in milk of cattle and sows is 3-6 times higher than the blood concentration about 6 hours following injection. In bovine and porcine lungs maximum tylosin concentrations of 7-8 times higher than the maximum concentrations in serum were found at 6-24 hours following intramuscular injection. In cattle (whether in heat or not) the Mean Residence Time (MRT) in uterus secretions of tylosin injected by intravenous route at a dose rate of 10 mg/kg was about 6-7 times higher than the one measured in serum. This illustrates that in uterine secretions a single tylosin injection at a dose rate of 10 mg/kg during 24 hours can result in concentrations exceeding the MIC90 of tylosin for Arcanobacterium pyogenes, one of the pathogens frequently isolated when metritis is diagnosed in cattle.

Tylosin is eliminated in unchanged form in bile and urine.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Benzyl alcohol (E1519)

Propylene glycol (E1520)

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

Store in the original package.

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

Do not store above 25°C.

Do not freeze.

6.5 Nature and composition of immediate packaging

50 ml, 100 ml or 250 ml colourless type II glass vials closed with a bromobutyl rubber stopper and aluminium cap.

One vial per carton.

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

Vetoquinol UK Ltd.

Vetoquinol House

Great Slade

Buckingham Industrial Park

Buckingham

Buckinghamshire

MK18 1PA

8. MARKETING AUTHORISATION NUMBER

Vm 08007/4144

9. DATE OF FIRST AUTHORISATION

19 May 2016

10. DATE OF REVISION OF THE TEXT

May 2016

Approved: 19/05/2016