1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Aivlosin 42.5 mg/g oral powder for pigs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance:

Tylvalosin (as tylvalosin tartrate) 42.5 mg/g

Excipients:

Qualitative composition of excipients and other constituents

Hydrated magnesium silicate (sepiolite)

Wheat flour

Hydroxypropyl cellulose

Non-fat soyabean powder

A beige granular powder.

3. CLINICAL INFORMATION

3.1 Target species

Pigs

3.2 Indications for use for each target species

The presence of the disease in the group must be established before the product is used.

• Treatment and metaphylaxis of swine enzootic pneumonia caused by Mycoplasma hyopneumoniae in pigs. At the recommended dose, lung lesions and weight loss are reduced but infection with Mycoplasma hyopneumoniae is not eliminated.

• Treatment of porcine proliferative enteropathy (ileitis) caused by Lawsonia intracellularis in groups where there is a diagnosis based on clinical history, postmortem findings and clinical pathology results.

• Treatment and metaphylaxis of swine dysentery, caused by Brachyspira hyodysenteriae in groups where the disease has been diagnosed.

3.3 Contraindications

Do not use in cases of hypersensitivity to macrolide antibiotics or to any of the excipients.

3.4 Special warnings

Acute cases and severely diseased pigs with reduced food or water intake should be treated with a suitable injectable product.

Generally, strains of B. hyodysenteriae have higher minimal inhibitory concentration (MIC) values in cases of resistance against other macrolides, such as tylosin. The clinical relevance of this reduced susceptibility is not fully explored.

Cross-resistance has been shown between tylvalosin and other macrolides. Use of the veterinary medicinal product should be carefully considered when susceptibility testing has shown resistance to tylvalosin because its effectiveness may be reduced.

3.5 Special precautions for use

Special precautions for safe use in the target species:

Use of the product should be in accordance with official, national and regional antimicrobial policies.”

An antibiotic with a lower risk of antimicrobial resistance selection (lower AMEG category) should be used for first line treatment where susceptibility testing suggests the likely efficacy of this approach.

Use of the product should be based on identification and susceptibility testing of the target pathogen(s). If this is not possible, therapy should be based on epidemiological information and knowledge of susceptibility of the target pathogens at farm level, or at local/regional level.

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

Tylvalosin has been shown to cause hypersensitivity (allergic) reactions in laboratory animals; therefore, people with known hypersensitivity to tylvalosin should avoid contact with this product.

When mixing the veterinary medicinal product and handling the medicated oral powder, direct contact with eyes, skin and mucous membranes should be avoided. Personal protective equipment consisting of impervious gloves and a half-mask respirator conforming to European Standard EN 149 or a non- disposable respirator conforming to European Standard EN 140 with a filter conforming to European Standard EN 143 should be worn when mixing the product. Wash contaminated skin.

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

Special precautions for the protection of the environment:

Not applicable.

3.6 Adverse events

None known.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See also the package leaflet for respective contact details.

3.7 Use during pregnancy, lactation or lay

Pregnancy and lactation

Use only in accordance with benefit-risk assessment by the responsible veterinarian.

No signs of adverse effects were observed in sows or their offspring when tylvalosin was administered orally and continuously for 195 days to sows, from before insemination to weaning, at an inclusion rate of 150 mg tylvalosin per kg water, corresponding to an average of 4.6 mg tylvalosin per kg body weight per day.

Laboratory studies in animals have not produced any evidence of a teratogenic effect. Maternal toxicity in rodents has been observed at doses of 400 mg tylvalosin per kg bodyweight and above. In mice, a slight reduction in the foetal bodyweight was seen at doses causing maternal toxicity.

3.8 Interaction with other medicinal products and other forms of interaction

None known.

3.9 Administration routes and dosage

For use in individual pigs on farms where only a small number of pigs are to receive the treatment. Larger groups should be treated with medicated feeding stuff containing the premix.

For treatment and metaphylaxis of swine enzootic pneumonia

The dose is 2.125 mg tylvalosin per kg bodyweight per day for 7 consecutive days. Secondary infection by organisms such as Pasteurella multocida and Actinobacillus pleuropneumoniae may complicate enzootic pneumonia and require specific medication.

For treatment of porcine proliferative enteropathy (ileitis)

The dose is 4.25 mg tylvalosin per kg bodyweight per day for 10 consecutive days.

For treatment and metaphylaxis of swine dysentery

The dose is 4.25 mg tylvalosin per kg bodyweight per day for 10 consecutive days.

This is achieved by thoroughly mixing the veterinary medicinal product into approximately 200– 500 g of feed and then thoroughly mixing this pre-mixture into the remainder of the daily ration. Scoops of 2 sizes are provided for measuring the correct amount of veterinary medicinal product for mixing with the daily ration, according to the schedule below. The feed containing the oral powder should be provided as the sole ration for the periods recommended above.

The pig to be treated should be weighed and the amount of feed that the pig is likely to consume should be estimated, based on a daily feed intake equivalent to 5% of bodyweight. Consideration must be given to pigs whose daily feed intake is reduced or restricted. The correct quantity of the veterinary medicinal product should be added to the estimated quantity of daily ration for each pig, in a bucket or similar receptacle, and thoroughly mixed.

The veterinary medicinal product should only be added to dry non-pelleted feed.

Swine enzootic pneumonia 2.125 mg/kg bodyweight Bodyweight range (kg) Scoop size Number of scoops 7.5–12 1 ml 1 13–25 1 ml 2 26–38 1 ml 3 39–67 5 ml 1 68–134 5 ml 2 135–200 5 ml 3 201–268 5 ml 4

PPE (ileitis) and swine dysentery 4.25 mg/kg bodyweight Bodyweight range (kg) Scoop size Number of scoops 7.5–12 1 ml 2 13–19 1 ml 3 20–33 5 ml 1 34–67 5 ml 2 68–100 5 ml 3 101–134 5 ml 4 135–200 5 ml 6 201–268 5 ml 8

NB: A level scoop of the product should be measured

3.10 Symptoms of overdose (and where applicable, emergency procedures and antidotes)

No signs of intolerance have been observed in growing pigs at up to 10 times the recommended dose.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable

3.12 Withdrawal periods

Meat and offal: 2 days.

4. PHARMACOLOGICAL INFORMATION

4.1 ATCvet code:

QJ01FA92

4.2 Pharmacodynamics

Tylvalosin tartrate is a macrolide antibiotic that has antibacterial activity against Gram-positive, some Gram-negative organisms and mycoplasma. It acts by inhibiting protein synthesis in bacteria cells.

Macrolide antibiotics are metabolites or semi-synthetic derivatives of metabolites of soil organisms obtained by fermentation. They have differently sized lactone rings and are basic due to the dimethylamino group. Tylvalosin has a sixteen-membered ring.

Macrolides interfere with protein synthesis by reversibly binding to the 50S ribosome subunit. They bind to the donor site and prevent the translocation necessary for keeping the peptide chain growing. Their effect is essentially confined to rapidly dividing organisms. Macrolides are generally considered bacteriostatic and mycoplasmastatic.

It is considered that there are multiple mechanisms responsible for resistance development to macrolide compounds, namely alteration of the ribosomal target site, utilisation of active efflux mechanism and production of inactivating enzymes.

Resistance to tylvalosin by Mycoplasma hyopneumoniae and Lawsonia intracellularis has not been reported or found in the field to date. No breakpoint for Brachyspira hyodysenteriae has been established. Generally, strains of B. hyodysenteriae have higher MIC values in cases of resistance against other macrolides, such as tylosin. The clinical relevance of this reduced susceptibility is not fully explored.

Cross-resistance between tylvalosin and other macrolide antibiotics cannot be excluded.

In addition to their antimicrobial properties, immunomodulating and anti-inflammatory effects have been described for some macrolides in experimental studies. Tylvalosin has been shown to induce apoptosis of porcine neutrophils and macrophages, promote efferocytosis and inhibit proinflammatory

CXCL-8, IL1α and LTB4 production, while inducing the release of pro-resolving Lipoxin A4 and Resolvin D1 in vitro.

4.3 Pharmacokinetics

Tylvalosin tartrate is rapidly absorbed after oral administration of the veterinary medicinal product.

After administration of the recommended dose lung concentrations of 0.060–0.066 mcg/ml were found at 2 and 12 hours post-treatment. The parent compound is widely distributed in the tissues with the highest concentrations found in the lungs, bile, intestinal mucosa, spleen, kidney and liver.

There is evidence that the concentration of macrolides is higher at the site of infection than in plasma, in particular in neutrophils, alveolar macrophages and alveolar epithelial cells.

In vitro metabolism studies have confirmed that the parent compound is rapidly metabolised to 3O-acetyltylosin. In a trial with ¹⁴C-labeled veterinary medicinal product administered at 2.125 mg/kg to pigs for 7 days, over 70% of the dose was excreted in the faeces, with urinary excretion accounting for 3 to 4% of the dose.

5. PHARMACEUTICAL PARTICULARS

5.1 Major incompatibilities

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

5.2 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years.

Shelf life after first opening of the immediate packaging: 4 weeks.

Feed to which the oral powder has been added should be replaced if not consumed within 24 hours.

5.3 Special precautions for storage

Store below 30 ºC.

Store in the original container.

Keep the container tightly closed.

5.4 Nature and composition of immediate packaging

One aluminium foil/polyester laminated bag containing 500 g. Scoops of 1 ml and 5 ml are attached.

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

Medicines should not be disposed of via wastewater.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

6. NAME OF THE MARKETING AUTHORISATION HOLDER

ECO Animal Health Europe Limited

7. MARKETING AUTHORISATION NUMBER(S)

EU/2/04/044/013

8. DATE OF FIRST AUTHORISATION

Date of first authorisation: 09/09/2004

9. DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

{MM/YYYY}

10. CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product subject to prescription.

Detailed information on this veterinary medicinal product is available in the Union Product Database (https://medicines.health.europa.eu/veterinary).