SUMMARY OF PRODUCTS CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Imizol 85mg/ml Solution for Injection

Each ml contains:

Active Substance(s): mg

Imidocarb 85.00

(as Imidocarb dipropionate 121.15)

For a full list of excipients see section 6.1

3. PHARMACEUTICAL FORM

Solution for Injection

Clear amber aqueous liquid

4. CLINICAL PARTICULARS

4.1 Target species

Cattle

4.2 Indications for Use:

For the treatment and prevention of bovine babesiosis (Redwater fever - Babesia divergens infection) only.

• Imizol must not be administered intravenously or intramuscularly.

• Repeat doses of Imizol must not be given.

4.4 Special warnings for each target species

Not for use in any other species.

4.5 Special precautions for use

i. Special precautions for use in animals

Estimate bodyweight carefully and do not exceed the recommended dosage.

ii. Special precautions for the person administering the veterinary medicinal product to animals

Do not use if under medical advice not to work with compounds which may exhibit anti-cholinesterase activity.

Wash splashes of the product off the skin and eyes immediately. Wear suitable protective clothing (ie impermeable gloves) when using the product.

Seek medical advice immediately if adverse signs indicative of anti-cholinesterase activity are experienced by operators.

4.6 Adverse reactions (frequency and seriousness)

Animals may show cholinergic signs after dosing. It may be possible to alleviate these side effects by treatment with atropine sulphate.

While side-effects (salivation, discomfort, muscle tremors, tachycardia, cough, colics) are rare, they do occur and deaths from anaphylactoid reactions have been recorded following product use.

4.7 Use during pregnancy, lactation or lay

Treatment of pregnant animals has demonstrated that although the compound does cross the placental barrier there does not appear to be an adverse effect on the foetus or calf.

4.8 Interaction with other medicinal products and other forms of interaction

None known

4.9 Amount(s) to be administered and administration route

The product is for subcutaneous injection administration only. The recommended dose regimen is as follows:

Indication	Dose
Therapy (treatment)	1.0 ml/ 100 kg body weight (0.85 mg imidocarb/kg bw)
Prevention*	2.5 ml/ 100 kg body weight (2.125 mg imidocarb/kg bw)

* For therapy of in-contact animals known to be exposed to an infection.

The product should be administered on a single occasion only. Do not administer by the intramuscular or intravenous route. Do not inject more than 10 ml per injection site.

4.10 Overdose (symptoms, emergency procedures, antidotes),

At about 1.75x overdose of the recommended dose signs consistent with cholinergic activity started to manifest themselves.

Death can result at doses of 5x the recommended therapeutic dose or greater.

4.11 Withdrawal period(s)

Animals must not be slaughtered for human consumption during treatment. Cattle may be slaughtered for human consumption only after a period of at least 213days from treatment.

Milk for human consumption must not be taken during treatment. Milk must not be taken for human consumption from cattle until after at least 21 days from treatment.

5. PHARMACOLOGICAL PROPERTIES

Imidocarb dipropionate is a substituted carbanilide, used as an antiprotozoan treatment for the control of Babesia spp.

Little is known about the mode-of-action of imidocarb dipropionate. It appears that imidocarb acts directly on the parasite, causing alteration in number and size of nuclei and in morphology (vacuolation) of the cytoplasm. The antiprotozoan activity is derived from the carbanilide acting on glycolyis of the parasite. This is the result of this class of drugs giving rise to hypoglycaemia in the host. Babesiaas well as many other parasites like trypanosomes depend upon host glucose for aerobic glycolysis. There is also a selective blocking effect on the replication of the quinetoplastic DNA of the parasite.

5.1 Pharmacokinetics

ATC Vet Code: QP51AE01

Pharmacokinetic studies have been conducted with imidocarb dipropionate and have demonstrated that it has a long duration of activity, a result of it binding to plasma and tissue protein.

Imidocarb dipropionate is poorly absorbed when administered orally. Studies in rats, dogs and monkeys demonstrated that kidney and liver were the target organs, with it having the greatest affinity for kidney in rats and liver in the dog.

A radio-labelled study in lactating and non-lactating cattle, with imidocarb dipropionate being administered subcutaneously at a dose rate of 3 mg/kg body weight, demonstrated that imidocarb dipropionate was slowly excreted so that by 10 days post-dosing less than half the dose had been excreted. Main route of excretion was via the urine. Blood levels peaked at a mean level of 1.3 ppm equivalents 1 hour after injection. Milk levels peaked at a mean 0.37 ppm imidocarb dipropionate equivalents 24 hours post administration, and then depleted with a half-life of about 24 hours. All excreted material was mostly parent compound.

Other work has shown that imidocarb dipropionate can pass the placental barrier.

Studies have been conducted in sheep where imidocarb dipropionate was administered by intravenous injection at a dose rate of 2 mg/kg bodyweight. This was found to produce a peak level in plasma of 10.8 mg/mL, dropping to 1.9 mg/mL within an hour. It was also found that imidocarb dipropionate binds to plasma proteins, and detectable amounts were found in all major tissues up to four weeks after intramuscular injection.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Propionic acid (for pH adjustment)

Water for Injection

6.2 Incompatibilities

None known

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 18 months

Shelf life after first opening of the immediate packaging: 28 days

6.4 Special precautions for storage

Do not store above 25°C. Protect from light. Do not freeze.

This product does not contain an antimicrobial preservative.

Following withdrawal of first dose, use the product within 28 days. Discard unused material.

Avoid introduction of contamination.

6.5 Nature and composition of immediate packaging

100ml amber glass (Type I) vial with blue rubber chlorobutyl bung with clear lacquered aluminium overseal.

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products, if any

Any unused veterinary medicinal product or waste material derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Intervet UK Ltd

Walton Manor

Walton

Milton Keynes

MK7 7AJ

8. MARKETING AUTHORISATION NUMBER

Vm01708/4576

9. DATE OF FIRST AUTHORISATION

Date: 18 July 1990

10. DATE OF REVISION OF THE TEXT

Date: December 2011

When used for prevention, Imizol should be administered when clinical signs of the disease are observed in one or two cattle of a group or at the time of moving susceptible cattle into an area of known Babesia challenge. The entire group of animals should be dosed to provide protection against babesiosis, and all must be kept to the withhold times shown above. The product gives protection for a period of up to 4 weeks depending on the severity of challenge. During this time, only if the challenge is adequate will immunity be established.

Prescribing and/or treating Veterinarians should notify their Divisional Veterinary Manager/Regional Veterinary Lead٭with the name and address of the farmer on whose farm the product is to be administered. They should also inform the farmer that they must notify the DVM/RVL when treated animals are either to be slaughtered or their milk is to be used for human consumption.

٭Details from the DVM/RVL at the local office.