SUMMARY OF THE PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Exflow 10 mg/g powderfor use in drinking waterfor cattle (calves), pigs, chickens, turkeys and ducks

Exflow Vet 10 mg/g powderfor use in drinking waterfor cattle (calves), pigs, chickens, turkeys and ducks (BE/DE/AT/NL)

Exflow (FR)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gram contains:

Active substance:

Bromhexine................................................ 9.11 mg

(as bromhexine hydrochloride 10.00 mg)

Excipients:

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for use in drinking water

White to slightly beige powder

4. CLINICAL PARTICULARS

4.1 Target species

Cattle (Calves), pigs, chickens, turkeys and ducks.

4.2 Indications for use, specifying the target species

Mucolytic treatment of congested respiratory tract.

4.3 Contraindications

Do not use in cases of pulmonary oedema.

In case of serious lungworm infection, the drug should only be used 3 days after the commencement of the anthelmintic treatment.

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

4.4 Special warnings for each target species

None.

4.5 Special precautions for use

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

People with known hypersensitivity to bromhexine or any of the excipients should avoid contact with the veterinary medicinal product.

Avoid contact with skin and eyes.

In case of accidental eye contact, flush the affected eye with copious amounts of clean running water.

Wash hands and exposed skin after administering the product.

4.6 Adverse reactions (frequency and seriousness)

None known

4.7 Use during pregnancy, lactation or lay

Studies in laboratory animals have not produced evidence of foetotoxic effects or effects on fertility at the recommended dose. However this has not been specifically studied in the target species. Use only according to thebenefit-risk assessment by the responsible veterinarian.

4.8 Interaction with other medicinal products and other forms of interaction

The product may be used in conjunction with antibiotics and/or sulphonamides and bronchodilators.

Bromhexine modifies the distribution of antibiotics in the organism and increases their concentration in the respiratory system.

4.9 Amounts to be administered and administration route

To be administered orally

0.45 mg of bromhexine per kg bodyweight daily, equivalent to 5 g of product per 100 kg bodyweight per day administered for 3 to 10 consecutive days, in drinking water.

In order to obtain the correct dosage the concentration of bromhexine has to be adjusted accordingly.

The following formula may be used to calculate the required concentration of product (in milligrams of product per litre drinking water):

50.mg of the product per kg body weight and per day	x	Average body weight (kg) of animals to be treated	=... mg of the product per litre of drinking water
Average daily water intake (l/animal)

The required amount of product should be weighed as accurately as possible using suitably calibrated weighing equipment.

Recommendation for dilution:

• Prepare a relevant quantity of water in a container.

• Add the product to the water while stirring the solution.

• Prepare the solution with fresh water immediately before use.

When using a water proportionner, adjust the pump between 1% to 5% and adapt the volume of preparation accordingly. Do not set up the dosing pump below 1%.

When using a water tank, it is recommended to prepare a stock solution of at least 1g of product/L and to dilute it to the target final concentration.

The solubility of the product has been tested at the maximum concentration of 100 g/L at 20°C.

Turn off the water supply to the tank until all the medicated solution is consumed.

For example :

Prepare a stock solution at 1g of product/L, dilute 1/3 to obtain a medicated solution at 0.33g of powder/L eq to 1g of powder/3L.

For pigs, when administered during the meal, first dissolve the product in water and then add feed. Administration during the meal should be restricted to individual treatment or for treatment of a small group of animals. The preparation must be used immediately. Care should be taken that the intended dose will be completely ingested.

The intake of medicated waterdepends on the clinical condition of the animals.

Any unused medicated water should be discarded after 24 hours.

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

None known.

4.11 Withdrawal period(s)

Cattle (calves)

Meat and offal: 2 days

Not permitted for use in cows producing milk for human consumption.

Pigs

Meat and offal: Zero days.

Chickens, turkeys and ducks

Meat and offal: Zero days

Do not use in birds producing eggs for consumption, during and 4 weeks before the laying phase.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Expectorants, excl. combinations with cough suppressants, mucolytics.

ATCvet code:QR05CB02.

5.1 Pharmacodynamic properties

Bromhexine is a mucoregulator. By activating the secretion of the seromucous glands, bromhexine helps to re-establish the viscosity and elasticity of bronchial secretions in the tracheobronchial tree. In addition, its expectorant action encourages mobilisation of mucus and enables effective bronchial drainage, thereby improving the functioning and defence capability of the lung.

These two simultaneous actions lead to an abundant discharge and facilitate a productive cough.

It breaks down the network of acid glycoprotein fibres found in mucoid sputum, which are mainly responsible for the characteristic viscosity.

Bromhexine modifies the distribution of antibiotics in the organism and increases their concentration in the serum and in the nasal secretions (e.g. spiramycin, tylosin and oxytetracycline). When administered concomitantly with the product, antimicrobial agents should, nevertheless, not be underdosed.

5.2 Pharmacokinetic particulars

Absorption

In pigs, bromhexine is rapidly absorbed following oral administration with a peak plasma concentrations obtained in one to three hours. The concentration plateau is reached 12 hours after the second or third administration.

In cattle, plasma concentrations increase progressively over several hours following administration.

In turkeys or broilers, peak plasma concentrations are reached within 2 to 4 hours of oral administration.

Distribution

Due to the lipophilic character of bromhexine, it has a strong affinity for lipid tissues and a slow depletion profile from these tissues.

Metabolism

Bromhexine is largely metabolised into more polar compounds.

Elimination

The apparent total radioactivity plasma half-life elimination after the last administration is 20 to 30 hours in a pig, 40 to 50 hours in cattle and 40 to 50 hours in chickens and turkeys.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Citric acid anhydrous

Lactose monohydrate

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: 30 months

Shelf life after first opening the immediate packaging: 3 months

Shelf life after dilution in drinking water: 24 hours

6.4. Special precautions for storage

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

6.5 Nature and composition of immediate packaging

Polyethylene/ polyamide/ aluminium/polyethylene terephthalatebags closed by a zip: 500 g, 1 kg, 2.5kg, 5kg

White HDPE jars with a yellow polypropylene screw stopper: 500 g,1 kg

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

Ceva Animal Health Ltd

Unit 3, Anglo Office Park

White Lion Road

Amersham

Buckinghamshire

HP7 9FB

8. MARKETING AUTHORISATION NUMBER

Vm 15052/4073

9. DATE OF FIRST AUTHORISATION

07 October 2015

10. DATE OF REVISION OF THE TEXT

O ctober 2015

Approved: 07 October 2015