SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Methoxasol 20/100 mg/ml solution for use in drinking water for pigs and chickens.

FI/DK: Methoxasol vet 20/100 mg/ml solution for use in drinking water for pigs and chickens.

Each ml contains:

Active substances: Trimethoprim 20.0 mg

Sulfamethoxazole 100.0 mg

Excipients For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for use in drinking water.
Clear and yellow solution.

4. CLINICAL PARTICULARS

4.1 Target species

Pigs and chickens (broilers).

4.2 Indications for use, specifying the target species

Pigs:Treatment and prevention of respiratory infections caused by Actinobacillus pleuropneumoniaesusceptible to trimethoprim and sulfamethoxazole where the disease has been diagnosed in the herd.

Broilers:Treatment and prevention of respiratory infections caused by Escherichia colisusceptible to trimethoprim and sulfamethoxazole where the disease has been diagnosed in the flock.

4.3 Contraindications

Do not use in animals suffering from severe liver or kidney disease, oliguria or anuria.

Do not use in animals with impaired haematopoietic systems.

Do not use in case of known hypersensitivity to sulfonamides or trimethoprim.

4.4 Special warnings for each target species

Severely diseased animals can have a decreased appetite and water consumption. If necessary the concentration of the VMP in the drinking water should be adjusted to make sure that the recommended dosage is being consumed. However if the concentration of the product is increased too much, the intake of the medicated drinking water decreases

for palatability reasons. Therefore water intake should be monitored regularly, especially in broilers.

In case of insufficient uptake of water, pigs should be treated parenterally.

4.5 Special precautions for use

Special precautions for use in animals

Due to the likely variability (time, geographical) in susceptibility of bacteria for potentiated sulphonamides,occurrence of resistance of bacteriamay differ from country to country and even from farm to farm, and therefore bacteriological sampling and susceptibility testing are recommended.Use of the product should be based on culture and sensitivity of micro-organisms from diseased cases on farmor from recent previous experience on the farm.Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to sulfamethoxazole and trimethoprim and may also decrease the effectiveness of combinations of trimethoprim with other sulphonamides due to the potential for cross resistance.

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

During preparation and administration of the medicated drinking water, skin contact with the drug should be avoided. Therefore it is recommended to wear impermeable gloves e.g. rubber or latex when applying the product. Do not handle this product if you know you are allergic to trimethoprim or sulphonamides.

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

In the event of eye contact, rinse the eye with copious amounts of clean water and if irritation occurs, seek medical attention. In the event of accidental ingestion, seek medical advice. Wash hands and contaminated skin immediately after handling the product.

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

4.6 Adverse reactions (frequency and seriousness)

A diminished water intake in chickens may occur occasionally.

Hypersensitivity reactions can occur rarely.

4.7 Use during pregnancy, lactation or lay

Laboratory studies in rats conducted with trimethoprim have shown evidence of teratogenicity at higher doses that recommended therapeutic ones. The safety of the product during pregnancy and lactation has not been established in sows. The use of the product is not recommended in sows during pregnancy and lactation.

4.8 Interaction with other medicinal products and other forms of interaction

Do not combine with other veterinary medicinal products.

4.9 Amounts to be administered and administration route

The veterinary medicinal product is intended for oral administration with drinking water. The product can be added directly to the drinking water to prepare a therapeutic solution at the calculated concentration, but can also be used in a concentrated stock solution by adding 200 ml of the veterinary medicinal product per litre water and diluting this further if

required. Do not use this veterinary medicinal product undiluted or in higher concentrated stock solutions.

Pigs:25 mg TMPS per kg bodyweight per day for 3-4 days, corresponding to 1 ml of the veterinary medicinal product per 4,8 kg bodyweight per day. This corresponds to approximately 1 litre of the veterinary medicinal product in 500 L drinking water.

Based on the recommended dose, daily water consumption, and the number and weight of the pigs to be treated, the exact daily amount of the veterinary product can be calculated according to the following formula:

Mean body weight (kg) of pigs to be treated	=	xx ml veterinary product per l drinking water
Mean daily water consumption (l) per pig x 4.8

Broilers:33 mg TMPS per kg bodyweight per day for 3-4 days, corresponding to 1 ml of the veterinary medicinal product per 3,64 kg bodyweight per day. This corresponds to approximately 1 litre of the veterinary medicinal product in 750 L drinking water.

Based on the recommended dose, daily water consumption, and the number and weight of the birds to be treated, the exact daily amount of the veterinary product can be calculated according to the following formula:

Mean body weight (kg) of broilers to be treated	=	xx ml veterinary product per l drinking water
Mean daily water consumption (l) per bird x 3.64

One litre of the veterinary medicinal product weighs 1079 gram; therefore weight can also be used to measure the product quantity to be added in drinking water, according to the following formula:

Amount to be added in drinking water (g/L) = calculated ml/L x 1.079.

The daily amount is to be added to the drinking water such that all medication will be consumed in 24 hours. Medicated drinking water and stock solutions should be freshly prepared every 24 hours. During the treatment period animals should not have access to other water sources than the medicated waterthe dilution of which should be calculated to ensure that animals always have sufficient water available. To ensure a correct dosage body weight should be determined as accurately as possible to avoid underdosing. The uptake of medicated water depends on the clinical condition of the animals. In order to obtain the correct dosage the concentration of the veterinary medicinal products has to be adjusted accordingly.

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

A 2 ½ fold overdose is well tolerated by pigs.

In chicken an acute overdose will not occur because the birds will be reluctant to drink the strongly concentrated drinking water (too bitter taste if above 2 litres of the veterinary medicinal product per 1000 litre drinking water). Chronic overdose in chicken will result in a strongly diminished water- and feed intake and retarded growth.

Meat and offal:

Pigs: 5 days

Broilers: 6 days

Eggs:

Not authorised for use in laying birds producing eggs for human consumption.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antibacterials for systemic use - Sulfamethoxazole and trimethoprim

ATC vet code: QJ01EW11

5.1 Pharmacodynamic properties

In vitro trimethoprim is generally bacteriostatic and has a broad spectrum of activity against both gram-positive and gram-negative bacteria. A synergistic and bactericidal effect occurs when trimethoprim is combined with sulfamethoxazole, because trimethoprim and sulfamethoxazole inhibit sequential steps in the synthesis of tetrahydrofolic acid, an essential metabolic cofactor in bacterial synthesis of purine and, subsequently, DNA.

5.2 Pharmacokinetic particulars

Following oral administration both active ingredients are rapidly absorbed from the gut. The C_maxof sulfamethoxazole in pigs is approximately 6.2 µg/g. The C_maxof trimethoprim is 0.29 µg/g. The C_maxof sulfamethoxazole in chickens is approximately 9.0 µg/g, whereas that of trimethoprim is 0.12 µg/g.

High trimethoprim concentrations are found in the kidneys, the liver and the lungs. With the exception of the kidneys, sulfamethoxazole concentrations in the tissues are significantly lower than in the plasma. Protein binding for trimethoprim and sulfamethoxazole is not very high.

The drugs are primarily excreted through the kidneys (both actively and passively), but elimination also occurs through the faeces. Elimination is relatively fast both in poultry and pigs. Plasma elimination half-life for trimethoprim in poultry is less than 1 hour and that of sulfamethoxazole, approximately 1.5 hours. In pigs, elimination half-life for both substances is approximately 2.5 hours. Within 48 hours after the last medication trimethoprim, sulfamethoxazole and their metabolites are undetectable in urine and faeces.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Propylene glycol,

Sodium hydroxide (for pH adjustment),

Water, purified,

N-methyl-pyrrolidone

6.2 Incompatibilities

Solubility and stability of the veterinary medicinal product in drinking water are pH-dependent.

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: 3 years

Shelf-life after first opening the immediate packaging: maximum 1 year and never beyond the expiry date

Shelf-life after dilution or reconstitution according to directions: 24 hours

6.4. Special precautions for storage

Do not freeze

6.5 Nature and composition of immediate packaging

1000 ml HDPE bottle closed with a tamper-proof LDPE screw-cap.

5000 ml HDPE can closed with a tamper-proof HDPE screw-cap.

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 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 16849/4040

9. DATE OF FIRST AUTHORISATION

4 September 2012

September 2012