SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Apralan Soluble Powder for oral solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance:

Apramycin sulphate.

Bottle - Apramycin sulphate equivalent to 50g apramycin activity.

Sachet - Apramycin sulphate equivalent to 1g apramycin activity.

Bag - Apramycin sulphate equivalent to 1000g apramycin activity.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for Oral Solution

Light to medium brown granular powder.

4. CLINICAL PARTICULARS

4.1 Target species

Apralan Soluble Powder is indicated for use in calves, pigs and chickens.

4.2 Indications for use, specifying the target species

Apralan Soluble Powder is indicated for the treatment of bacterial enteritis associated with organisms susceptible to apramycin in pigs, colibacillosis and salmonellosis in calves Escherichia colisepticaemia in young chickens.

In vitro, the following organisms were susceptible to Apramycin at concentrations of 16 µg/ml or less:

i) Gram-positive bacteria

Staphylococcus aureus

ii) Gram-negative bacteria

Bordetella bronchiseptica

Escherichia coli

Campylobacter spp

Klebsiella spp

Salmonella spp

Proteus spp

Pseudomonas aeruginosa

Shigella sonnei

iii) Mycoplasma

Mycoplasma hyopneumoniae

4.3 Contraindications

Do not use in cases of known hypersensitivity to apramycin.

Do not use in cats.

4.4 Special warnings for each target species

None.

4.5 Special precautions for use

i. Special precautions for use in animals

Official, national and regional antimicrobial policies should be taken into account when the product is used.

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

Avoid inhaling the powder while preparing the medicate water.

Avoid contact with skin and eyes. In the event of skin contact, wash thoroughly with soap and water.

In the event of accidental eye contact, wash the affected eye with fresh running water and seek medical attention if irritation persists.

Wash hands after use.

4.6 Adverse reactions (frequency and seriousness)

None known.

4.7 Use during pregnancy, lactation or lay

Not intended for use in pregnant or lactating animals. However, laboratory studies in the rat and rabbit have not produced any evidence of a teratogenic effect.

More than four times the recommended dose was given to boars prior to and during breeding and to sows after the period of service, during gestation and early lactation. No adverse effects on fertility were seen.

4.8 Interaction with other medicinal products and other forms of interaction

Drinking systems should be clean and free of rust to avoid reduction of activity.

4.9 Amounts to be administered and administration route

The intake of medicated water depends on the clinical condition of the animals. In order to obtain the correct dosage, the concentration of Apralan Soluble Powder has to be adjusted accordingly.

Add the appropriate quantity of the product to 5-10 times its own volume of water. Stir well and allow the solution to stand for a few minutes and then stir again. When completely dissolved, add the full volume of drinking water and stir well.

Pigs:

To be administered via the drinking water. Treated pigs should consume sufficient medicated drinking water to obtain 7.5-12.5 mg apramycin activity per kg of bodyweight daily for seven days. This may be achieved by adding 1 small measure (4.2 cm³, equivalent to 1g apramycin activity) or one sachet per 20 litres of water. Filling the large measure provides 21.0 cm³(equivalent to 5g apramycin activity). The scoop provided with the 1 kg bag contains 25 g apramycin activity when tapped gently three times and levelled.

As a guide, average daily water consumption for fattening pigs is shown in the following table:

Bodyweight (kg)	Average Consumption (litres)	Approx. Galls
5	1.10	0.25
10	1.75	0.4

Calves:

To be administered in the drinking water, milk or milk replacer to receive 20-40 mg of apramycin activity per kg of bodyweight daily according to the severity of the disease. Continue treatment for five days. The full dose should be given once daily according to the following table:

Total Bodyweight to be treated	Apralan Soluble	Apramycin (activity g per day)
50 kg	1 to 2 small measures, or 1 to 2 sachets.	1.0 to 2.0 g
250 kg	1 to 2 large measures filled to upper level, or 5 to 10 sachets.	5.0 to 10.0 g
2500 kg	1 to 2 bottles	50.0 to 100.0 g

Solutions in milk and reconstituted milk replacer should be prepared immediately before use. Any medicated milk or milk replacer which is not consumed within one hour should be discarded.

Chickens:

To be administered in the drinking water to receive 250 or 500 mg/litre of apramycin activity for five days. This may be achieved by adding 50g apramycin activity per 100 to 200 litres of water.

Any medicated water which is not consumed within 24 hours should be discarded.

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

Pigs:

Pigs have been given up to nine times the recommended use level in their drinking water for 28 days with no untoward reaction.

Calves:

Calves were given apramycin in milk replacer daily for five days, at doses up to 120 mg/kg bodyweight (3-times recommended use level). There was no toxic effect.

Poultry:

There was no mortality when chickens were given a single oral dose of 1000 mg/kg bodyweight. Chickens were given up to 5 times the recommended level for 15 days with no untoward reaction.

4.11 Withdrawal period(s)

Pigs: Meat: 14 days

Calves: Meat: 28 days

Chickens: Meat: 7 days

Do not use in laying chickens when eggs are intended for human consumption.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group:Antibacterials for systemic use, Aminoglycoside antibacterials, Other aminoglycosides

ATCvet code:QJ01GB90

5.1 Pharmacodynamic properties

Apramycin is a broad-spectrum aminocyclitol antibiotic produced by a strain of Streptomyces tenebrarius. Apramycin is bactericidal at minimum inhibitory concentrations.

Apramycin is effective against both Gram-negative and Gram-positive bacteria and some strains of mycoplasma at concentrations of 16 µg/ml or less. It is effective against most field strains of Escherichia coli and salmonellae.

5.2 Pharmacokinetic particulars

The oral administration of apramycin is intended for antimicrobial activity within the gut; apramycin is poorly absorbed, particularly in older animals:

Absorption: Pigs. Nine mg of apramycin/kg bodyweight administered orally is well absorbed in 2-day old pigs, slightly absorbed in 4-week old pigs and not absorbed in 8-week old pigs.

Calves. Serum levels peak at approximately 6 hours with a value of 2.4 µg/ml following oral administration of 40 mg apramycin/kg bodyweight. Duration of serum activity is between 24 and 36 hours.

Distribution, Biotransformation and Excretion: Pigs. Very little metabolism of apramycin takes place in the animal. Dosing 10 kg pigs with ¹⁴C apramycin resulted in approximately 83% being recovered from the faeces, and 4% from the urine, as ¹⁴C apramycin.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None

6.2 Incompatibilities

None known.

6.3 Shelf life

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

Shelf-life after first opening the immediate container: 28 days (50g bottle and 1kg bag).

Shelf-life after dilution according to directions: 24 hours.

6.4. Special precautions for storage

Store in tightly closed original container.

Do not store above 25°C.

Store in a dry place.

Any medicated water which is not consumed within 24 hours should be discarded.

6.5 Nature and composition of immediate packaging

Apralan Soluble Powder is presented in high density polythene bottles with screw caps containing 50g apramycin activity. Bottles are supplied with a red polypropylene dose measurer, validated to dispense 1 g or 5 g of product, which snap-fits onto the bottle. Also presented in cartons containing 50 4-ply PET/polythylene/aluminium foil/surlyn ionomer sachets containing 1g apramycin activity, or a block bottomed laminated paper bag containing 1 kg apramycin activity.

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 national requirements.

7. MARKETING AUTHORISATION HOLDER

Eli Lilly and Company Limited

Elanco Animal Health

Lilly House

Priestley Road

Basingstoke

RG24 9NL

8. MARKETING AUTHORISATION NUMBER

Vm00006/4084

9. DATE OF FIRST AUTHORISATION

20 October 1992

10. DATE OF REVISION OF THE TEXT

September 2016

28 September 2016