Summary of Product Characteristics

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Soludox 500 mg/g powder for use in drinking water for turkeys

FR: Soludox 433 mg/g powder for use in drinking water for turkeys

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 gram of powder contains:

Active substance:

Doxycycline hyclate 500 mg, corresponding to 433 mg doxycycline

FR: Doxycycline 433 mg, corresponding to 500 mg doxycycline hyclate

Excipients:

For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Powder for use in drinking water

Yellow crystalline powder

4 CLINICAL PARTICULARS

4.1 Target species

Turkeys (broilers, breeders).

4.2 Indications for use, specifying the target species

Turkeys: treatment of clinical respiratory infections associated with Mycoplasma gallisepticum susceptible to doxycycline

4.3 Contra-indications

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

Do not use in animals with hepatic dysfunction.

4.4 Special warning for each target species.

The uptake of medication by animals can be altered as a consequence of illness. In case of insufficient uptake of drinking water, turkeys should be treated parenterally.

4.5 Special precautions for use

Special precautions for use in animals

Inappropriate use of the product may increase the prevalence of bacteria resistant to tetracycline due to the potential for cross resistance. Do not use when tetracycline resistance has been detected in the herd/flock.

Use of the product should be based on susceptibility testing and take into account official and local antimicrobial policies.

As eradication of the target pathogens may not be achieved, medication should therefore be combined with good management practices, e.g. good hygiene, proper ventilation, no overstocking.

Avoid administration in oxidised drinking equipment.

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

If you know you are allergic to the tetracycline class of antibiotics, special care should be taken when handling this product or the medicated solution.

During preparation and administration of the medicated drinking water, skin contact with the product and inhalation of dust particles should be avoided. Wear impermeable gloves (e.g. rubber or latex) and an appropriate dust mask (e.g. disposable half-mask respirator conforming to European Standard EN149) when applying the product.

In the event of eye or skin contact, rinse the affected area with large amounts of clean water and if irritation occurs, seek medical attention. Wash hands and contaminated skin immediately after handling the product.

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

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

Take measures to avoid producing dust when incorporating the product into water. Avoid direct contact with skin and eyes when handling the product to prevent sensitisation and contact dermatitis.

4.6 Adverse reactions (frequency and seriousness)

As for all tetracyclines, on rare occasions allergic reactions and photosensitivity may occur. If suspected adverse reactions occur, treatment should be discontinued. If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

4.7 Use during pregnancy, lactation or lay

Laboratory studies in rats and rabbits have not produced any evidence of a teratogenic, foetotoxic, maternotoxic effects.

4.8 Interaction with other medicinal products and other forms of interaction

Do not combine with antibiotics that are bactericidal e.g. penicillins or cephalosporins.

Absorption of doxycycline can be decreased in the presence of high quantities of calcium, iron, magnesium or aluminium in the diet. Do not administered together with antacids, kaolin and iron preparations.

It is advised that the interval between the administration of other products containing polyvalent cations should be 1-2 hours because they limit the absorption of tetracyclines.

Doxycycline increases the action of anticoagulants.

The solubility of the product is pH dependent and will precipitate if mixed in alkaline solution.

4.9 Amounts to be administered and administration route

Administration orally with the drinking water.

Dosage in turkeys: 25 mg doxycycline corresponding to 29 mg doxycycline hyclate per kg of body weight daily (equivalent to 58 mg product per kg of body weight), administered in the drinking water for 5 consecutive days.

The product should be administered continuously in the drinking water during the whole period of treatment. Based on the dose to be used, and the number and weight of the birds to be treated, the exact daily amount of product can be calculated. The following formula can be used to calculate the concentration of the product in drinking water:

58 mg product / kg body weight / day	X	Mean body weight (kg) of birds to be treated	= .... mg product per l drinking water
Mean daily water consumption (l) per bird

To ensure a correct dosage body weight should be determined as accurately as possible. The uptake of medicated drinking water depends on the clinical condition of the birds. In order to obtain the correct dosage the concentration of doxycycline has to be adjusted accordingly. The use of suitably calibrated weighing equipment is recommended if part packs are used. The daily amount is to be added to the drinking water such that all medication will be consumed in 24 hours. Medicated drinking water should be refreshed or replaced every 24 hours. It is recommended to prepare a concentrated pre-solution - approximately 100 grams product per litre drinking water - and to dilute this further to therapeutic concentrations if required. Alternatively, the concentrated solution can be used in a proportional water medicator. Solubility of the product is pH dependent and it may precipitate if it is mixed in hard alkaline drinking water. Use at minimum concentrations of 200 mg powder per litre drinking water in areas with hard alkaline drinking water(hardness above 10.2 °d and pH more than 8.1).During the treatment period birds should not have access to other water sources than the medicated water.

4.10 Overdose (symptoms, emergency procedures, antidotes)

No adverse effects were observed after administration of doxycycline to turkeys at the fivefold therapeutic dose for up to 10 days. If suspected toxic reactions do occur due to extreme overdose, the medication should be discontinued and appropriate symptomatic treatment should be initiated if necessary.

4.11 Withdrawal periods

Turkeys:

- Meat and offal: 12 days

- Eggs: Not to be used in birds producing eggs for human consumption

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antibacterial - Tetracycline. ATC vet code: QJ 01 AA 02

5.1 Pharmacodynamic properties

Doxycycline belongs to the group of the tetracycline antibiotics. These antibiotics have a broad spectrum of antimicrobial activity, sharing the same basic structure of polycyclic naphthacenecarboxamide.

Doxycycline is primarily a bacteriostatic drug. It exerts its action by inhibiting the protein synthesis of the bacterial cell. Inhibition of bacterial protein synthesis results in disturbance of all functions necessary for the life of bacteria. Especially cell-division and the formation of the cell wall are impaired.

Doxycycline is a broad-spectrum antibiotic, active against a large number of Gram-positive and Gram-negative, aerobe and anaerobe micro-organisms, Mycoplasma spp., Chlamydiae and Rickettsia.

The MIC90 of doxycycline against Mycoplasma gallisepticumstrains isolated in France, Germany and Hungary (2003-2009) was reported 0.5 µg/ml. The resistance rate of M. gallisepticumisolates against doxycycline is low.

Four resistance mechanisms acquired by microorganisms against tetracyclines in general have been reported: Decreased accumulation of tetracyclines (decreased permeability of the bacterial cell wall and active efflux), protein protection of the bacterial ribosome, enzymatic inactivation of the antibiotic and rRNA mutations (preventing the tetracycline binding to ribosome). Tetracycline resistance is usually acquired by means of plasmids or other mobile elements (e.g. conjugative transposones). Cross resistance between tetracyclines has also been described. Due to the greater liposolubility and greater facility to pass through cell membranes (in comparison to tetracycline), doxycycline retains a certain degree of efficacy against microorganisms with acquired resistance to tetracyclines.

5.2 Pharmacokinetic properties

In general, doxycycline is quite rapidly and extensively absorbed from the gastrointestinal tract, widely distributed in the organism, not metabolised to any significant extent and excreted mostly via the faeces.

Pharmacokinetics of doxycycline after single oral administration to turkeys is characterised by a quite rapid and substantial absorption from the gastrointestinal tract providing peak plasma concentrations between 1.5 to 7.5 hours depending on age and the presence of food. The drug is widely distributed in the organism with Vd values close to or greater than 1, and exhibits an elimination half-life in turkeys of 7.9 to 10.8 hours. The protein binding ratio at therapeutic plasma concentrations is in the range of 70-85%. The bioavailability in turkeys may vary between 25 and 64%, also depending on the age and feeding. The presence of food in the gastrointestinal tract determines a lower bioavailability compared to that obtained in the fasted state.

After continuous in-water administration of the product at dosages of 25 mg doxycycline/kg in turkeys for 5 days the average plasma concentrations over the whole treatment period were reported 2.24±1.02 µg/ml in turkeys. PK/PD analysis of AUC/MIC90 data resulted in >24 h values that meet the requirements for tetracyclines.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tartaric acid

6.2 Incompatibilities

Solubility of doxycycline is pH dependent. Precipitation will occur in an alkaline solution. In the absence of compatibility studies, this 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: 6 months

Shelf-life after dilution or reconstitution according to directions: After reconstitution with water, any product remaining after 24 hours should be discarded.

6.4 Storage precautions

This veterinary medicinal product does not require any special storage conditions.

Keep the bag tightly closed after first opening in order to protect from moisture.

6.5 Nature and composition of immediate packaging

Bags of 1 kg. Sachets of 100 grams packed per 10 in a carton box

1000 g bag: polyester, polyethylene, aluminium, polyethylene and an inner layer of polyethylene

1000 g bag: polyethylene terephtalic acid, aluminium, polyamide and an inner layer of polyethylene.

100 g sachet: polyester, polyethylene, aluminium and an inner layer of ionomer (surlyn).

Not all pack sizes may be marketed.

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

Eurovet Animal Health B.V.

Handelsweg 25

5531 AE Bladel

The Netherlands

8. MARKETING AUTHORISATION NUMBER

Vm 16849/4046

9. DATE OF FIRST AUTHORISATION

28 August 2012

10. DATE OF REVISION OF THE TEXT

August 2012