Vetmulin 450 Mg/G Granules For Use In Drinking Water For Pigs, Chickens And Turkeys

Summary

Revised: May 2016

AN. 01370/2014

		SUMMARY OF PRODUCT CHARACTERISTICS
1.	NAME OF THE VETERINARY MEDICINAL PRODUCT Vetmulin 450 mg/g granules for use in drinking water for pigs, chickens and turkeys. (All MS except FR)
	Vetmulin 364 mg/g granules for use in drinking water for pigs, chickens and turkeys. (FR)
2.	QUALITATIVE AND QUANTITATIVE COMPOSITION Active substance: Each gram contains Tiamulin hydrogen fumarate 450.0 mg (equivalent to tiamulin 364.2 mg) (All MS except FR) Each gram contains 364.2 mg tiamulin as 450.0 mg Tiamulin hydrogen fumarate (FR only) Excipients: For a full list of excipients: see section 6.1

3.	PHARMACEUTICAL FORM Granules for use in drinking water. White to pale yellow granules
4.	CLINICAL PARTICULARS
4.1	Target species Pigs, chickens and turkeys.
4.2	Indications for use (specifying the target species) Pigs For the treatment of swine dysentery caused by tiamulin-susceptible Brachyspira hyodysenteriae. For the treatment of enzootic pneumonia caused by tiamulin-susceptible Mycoplasma hyopneumoniae. Chickens Treatment and metaphylaxis of chronic respiratory infections (CRD) and air sacculitis caused by tiamulin-susceptible strains of Mycoplasma gallisepticum and Mycoplasma synoviae. Turkeys Treatment and metaphylaxis of infectious sinusitis and air sacculitis caused by tiamulin-susceptible strains of Mycoplasma gallisepticum and Mycoplasma synoviae and Mycoplasma meleagridis. The presence of the disease in the herd or flock must be established before use.
4.3	Contraindications Do not use in animals with known hypersensitivity to the active ingredient or to any of the excipients. Do not use in known cases of resistance to tiamulin. Do not administer products containing ionophores such as monensin, salinomycin or narasin during or for at least 7 days before or after treatment with the product.

4.4	Special warnings (for each target species) The uptake of medication by animals can be altered as a consequence of illness. In case of insufficient uptake of water, animals should be treated parenterally using an appropriate injectable product. Repeated use should be avoided by improving management practice and thorough cleansing and disinfection.

4.5	Special precautions for use
			Special precautions for use in animals Due to the likely variability (time, geographical) in the occurrence of resistance of bacteria for tiamulin, 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 tiamulin and may decrease the effectiveness of treatment with other pleuromutilins due to the potential for crossresistance. Strategic treatment should be limited to animals where tiamulin susceptible agents have been isolated in the herd or flock.
			Special precautions for the person administering the veterinary medicinal product to animals Direct contact with the skin, eyes and mucous membranes should be avoided by wearing overalls, impermeable rubber gloves and safety glasses when preparing or handling the product. In case of accidental eye contact, rinse the eyes thoroughly with clean running water immediately. Seek medical advice if irritation persists. When handling the product, inhalation of the dust must be avoided by wearing a disposable half-mask respirator conforming to European Standard EN 149 or a non-disposable respirator to European Standard EN 140 with a filter to EN 143. Contaminated clothing should be removed and any splashes on to the skin should be washed off immediately. Wash hands after use. Accidental ingestion should be avoided. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or label to the physician. People with known hypersensitivity to tiamulin should avoid contact with the product.
4.6	Adverse reactions (frequency and seriousness) Pigs On rare occasions, hypersensitivity to tiamulin following oral administration is reported in terms of increased salivation, mild oedema, acute dermatitis with cutaneous erythema and intense pruritus. The adverse reactions are often mild and transient but on very rare occasions may be serious and can lead to apathy or death. If these typical side effects occur, stop treatment immediately and clean animals and pens with water. Normally, the animals recover fast thereafter. Symptomatic treatment such as electrolyte therapy and an anti-inflammatory therapy may be useful. Chickens and turkeys Water intake may be depressed during the administration of tiamulin to birds. It does not appear to have any adverse effect on overall performance of the birds or efficacy of the product.
4.7	Use during pregnancy, lactation or lay Pigs The product can be used during pregnancy and lactation. Chickens and turkeys The product can be administered in laying and breeding birds as no negative effects on lay, fertility or hatchability were noticed in chickens and turkeys.

4.8	Interaction with other medicinal products and other forms of interaction Tiamulin is known to produce clinically important – often lethal – interactions with ionophore antibiotics. Therefore, animals should not receive products containing monensin, narasin, salinomycin during or at least 7 days before and after treatment with the product. Severe growth depression, ataxia, paresis or death may result. In order to avoid interactions between tiamulin and incompatible ionophores, the feed mill supplying the feed should be notified that tiamulin will be used and that these products should not be included in the feed or contaminate the feed. The feed should be tested for the ionophores prior to use if there is any suspicion that contamination of the feed might occur. If an interaction does occur, stop tiamulin water medication immediately and replace with fresh water. Remove contaminated feed as soon as possible and replace with feed not containing the tiamulin-incompatible ionophores. Concomitant use of tiamulin and the ionophore anticoccidial maduramicin is not recommended since it may lead to a mild to moderate growth depression in chickens. The situation is transient and recovery normally occurs within 3-5 days following withdrawal of tiamulin treatment. This does not seem to occur with the ionophores lasalocid and semduramicin. Tiamulin may lessen the antibacterial activity of ß-lactam antibiotics whose action is dependent on bacterial growth.

4.9

Amount(s) to be administered and administration route

For oral administration through the drinking water.

Chickens:

25 mg tiamulin hydrogen fumarate per kg bodyweight per day (equivalent to 5.5g of the product per 100 kg bw per day) for 3 to 5 consecutive days.

Turkeys:

40 mg tiamulin hydrogen fumarate per kg bodyweight per day (equivalent to 8.9g of the product per 100 kg bw per day) for 3 to 5 consecutive days.

Pigs:

Swine dysentery caused by Brachyspira hyodysenteriae:

8.8 mg tiamulin hydrogen fumarate per kg bodyweight per day (equivalent to 1.9 g of the product per 100 kg bw per day) for 5 consecutive days.

Enzootic pneumonia caused by Mycoplasma hyopneumoniae

15-20 mg tiamulin hydrogen fumarate per kg bodyweight per day (equivalent to 3.3-4.4 g of the product per 100 kg bw per day) for 5 consecutive days.

The uptake of medicated water depends on the actual body weight, the water consumption, the clinical condition of the animals, the environment, the age and the kind of feed provided. In order to obtain the correct dosage, the concentration of tiamulin should be calculated, as follows:

…. mg of the product
per kg body weight and day

Average body weight (kg)

=....mg of the product per litre of drinking water

Average daily water intake (l/animal)

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

Use suitably calibrated weighing equipment to weigh the necessary amount of product.

The product can be added directly to the required volume of drinking water or a concentrated solution can be prepared to be diluted to the final concentration afterwards.

The maximum solubility of the product is 10 gram/liter.

Medicated drinking water and stock solutions should be freshly prepared every 24 hours. Do not use rusty receptacles for preparation of the medicated drinking water. The medicated water should be the only source of drinking water for the animals for the entire duration of the treatment period. After the end of the medication period, the water supply system should be cleaned appropriately to avoid intake of sub-therapeutic amounts of the active substance.

Water intake may be depressed during the administration of tiamulin to birds. It appears to be concentration dependent with 0.025% tiamulin reducing intake by approximately 15%. Water intake should be monitored at frequent intervals during medication.

If there is no response to treatment within 3 days, the diagnosis should be re-considered and treatment should be changed, if necessary.

4.10

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

Chickens and turkeys:

Tiamulin hydrogen fumarate has a relatively high therapeutic index in birds. The probability of an overdose is low since water intake, and therefore tiamulin intake, is reduced at high doses. The LD₅₀ is 1290 mg/kg in chickens and is 840 mg/kg in turkeys.

The clinical signs of toxicity in chickens are vocalisation, clonic cramps and lying in a lateral position. Signs in turkeys are: clonic cramps, lateral or dorsal lying position, salivation and ptosis.

Pigs:

A single oral dose of 100 mg/kg BW caused hyperpnoea and abdominal complaints in pigs. At a dose of 150 mg/kg the only effects on the central nerve system was lethargy. A dose of 55 mg/kg during 14 days caused increased salivation and a mild irritation of the stomach. Tiamulin hydrogen fumarate has a relatively high therapeutic index in pigs. The minimum lethal dose has not been established in pigs.

If suspected adverse reactions do occur due to overdose, the medication should be discontinued and appropriate symptomatic treatment should be initiated.

4.11

Withdrawal period(s)

Pigs

Meat and offal: 5 days

Chickens

Meat and offal: 3 days

Eggs: Zero days

Turkeys

Meat and offal: 5 days

PHARMACOLOGICAL OR IMMUNOLOGICAL PROPERTIES

ATC Vet Code: QJ01XQ01

Pharmacotherapeutic group:

Antibacterials for systemic use

Pleuromutilins

5.1	Pharmacodynamic properties Tiamulin hydrogen fumarate is a semi-synthetic diterpene antibiotic. The mode of action is by inhibition of ribosomal protein synthesis.It is a bacteriostatic antibiotic and the spectrum of activity includes: mycoplasma and spirochetes, in particular Brachyspira hyodysenteriae Tiamulin is bacteriostatic at therapeutic concentrations and has been shown to act at the 70S ribosome. The primary binding site is on the 50S subunit and there is possibly a secondary site where the 50S and 30S subunits join. Tiamulin appears to inhibit microbial protein production by producing biochemically inactive initiation complexes, which prevent elongation of the polypeptide chain. In vitro research has shown that resistant bacterial mutants can be created through multi step resistance. Development of resistance in mycoplasmas is slower. Resistance against B. hyodysenteriae has been seen, and can vary geographically. Cross resistance between tiamulin and tylosin tartrate has been reported: micro-organisms that are resistant for tiamulin, are also resistant for tylosin tartrate, but not vice versa. Resistance in Brachyspirae hyodysenteriae can be caused by a point mutation in the 23S rRna gene.

5.2	Pharmacokinetic particulars Tiamulin is well absorbed from the gastrointestinal tract of chickens and turkeys. Chicken After the oral administration of 25 mg tiamulin/kg BW, a C_max of 1.7 µg/ml was measured after 4 hours (t_max). After the administration of medicated drinking water at 250 ppm (250 mg/L tiamulin hydrogen fumarate) to chickens during 48 hours, average concentrations in the serum were 0.78 µg/ml (0.45 - 1.4 µg/ml). There is a very good distribution in the tissues. Approximately 50% (45% - 52%) of the tiamulin is bound to serum proteins. Tiamulin is rapidly metabolised in the liver (hydroxylation, de-alkalysation, hydrolysis). The excretion is through the bile and faeces (55-65%). The remainder is excreted through the urine. The elimination is biphasic: more than 99% is excreted within 24 hours, while the remaining 1% is not excreted until 6 to 8 days. Turkey After the oral administration of 25 mg tiamulin/kg BW, a C_max of 1.08 µg/ml was measured after 4 hours (t_max). After the administration of medicated drinking water at 250 ppm (250 mg/L tiamulin hydrogen fumarate) to turkeys, average concentrations in the serum were 0.36 µg/ml (0.22 - 0.5 µg/ml). Pigs Tiamulin is well absorbed from the gastrointestinal tract of pigs. 2-4 hours (t_max) after the oral administration of 10 mg tiamulin/kg BW, a C_max of 1 µg/ml was measured. There is a very good distribution in the tissues. There is accumulation in lungs and in the colon. 30-50% of the tiamulin is bound to serum proteins. Tiamulin is rapidly metabolised in the liver (hydroxylation, de-alkalysation, hydrolysis). At least 16, biologically inactive metabolites have been identified. The excretion is through the bile and faeces (70-85%). The remainder is excreted through the urine (15-30%).
5.3	Environmental properties
	Tiamulin hydrogen fumarate is persistent in soils
6.	PHARMACEUTICAL PARTICULARS

6.1	List of excipients Povidone Lactose monohydrate

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

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: 3 months. Shelf life after dilution or reconstitution according to directions: 24 hours.

6.4	Special precautions for storage Do not refrigerate or freeze. Store in original container.

6.5	Nature and composition of immediate packaging Block bottomed zipped 1 kg bag of polyethylene terephthalate/aluminium/low density Polyethylene.

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

	Huvepharma N.V. Uitbreidingstraat 80 Antwerpen B-2600 Belgium

8.	MARKETING AUTHORISATION NUMBER Vm 30282/4002

9.	DATE OF FIRST AUTHORISATION 19 March 2009

10.	DATE OF REVISION OF THE TEXT May 2016 24 May 2016

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