Azaporc 40 mg/ml Solution for Injection for Pigs

Composition

Each ml contains:

Active substance:

Azaperone 40.0 mg

Excipients:

Sodium metabisulfite (E223) 2.0 mg

Methyl parahydroxybenzoate (E218) 0.5 mg

Propyl parahydroxybenzoate 0.05 mg

For the full list of excipients, see section 6.1.

6.1 List of excipients

Sodium metabisulfite (E223)

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate

Tartaric acid

Sodium hydroxide (for pH-adjustment)

Water for injections

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Pharmaceutical form

Solution for injection.

A clear, pale yellow aqueous solution.

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Pharmacological properties

Pharmacotherapeutic group: Nervous system, psycholeptics, antipsychotics, butyrophenone derivatives ATCvet Code: QN05AD90

5.1 Pharmacodynamic properties:

Azaperone is a neurolepticum from the group of butyrophenones, which is used for pigs due its sedative and anti-aggressive effects.

It blocks central and peripheral dopamine receptors and causes dosage-dependent sedation. Higher dosages trigger extrapyramidal-motor symptoms, such as catalepsy. An apomorphine-antagonising antiemetic effect has been demonstrated. Restraint of the hypothalamic heat-regulating centre in combination with a simultaneous expansion of the peripheral blood vessels causes a slight decrease in temperature. Azaperone counteracts the respiratory depressive effect of opiates and results in deeper breathing of the pigs after therapeutic dosages. With the elimination of the inhibiting effect of dopamine, a prolactin release occurs and after continued use, particularly with rats, changes to the pituitary gland, female reproductive organs and mammary glands occur.

Azaperone still influences the central and peripheral noradrenergic system. It causes a minor bradycardia with reduced cardiac output and a dilatation of the peripheral blood vessels with a decrease in blood pressure. In high concentrations, azaperone antagonises histamine and serotonin.

In pigs, sedation for 1 to 3 hours takes effect within 5 to 10 minutes after therapeutic dosages. All azaperone effects subside after 6 to 8 hours.

5.2 Pharmacokinetic particulars:

Parentally administered azaperone distributes quickly and reaches maximum values in the blood, brain and liver after 30 minutes. Levels reached in the brain are 2 to 6 times higher than in the blood. The maximum plasma concentration of the total of azaperone and its metabolites occurs after 45 minutes. Elimination from the plasma takes place in two phases with half-life values of 20 and 150 minutes for azaperone and 1.5 and 6 hours for azaperone and metabolites.

Azaperone is metabolised quickly. Only about 12 % of the dosage remains unchanged 4 hours after subcutaneous injection. The main metabolite azaperol arises with reduction of the butanone component. Its concentration is higher in most body tissues than that of azaperone, but azaperone is more prevalent at the injection site. Additional degradation paths in pigs are the hydroxylation of the pyridine ring and oxidative dearylation, as a result of which an N-formylation of the piperazine ring can occur. The metabolite patterns are the same in the various body tissues; only azaperone and azaperol were found at the injection site.

Azaperol has about ¼ of the sedative and about 1/30 of the temperature-reducing effect, α-(4-fluorphenyl)-1-piperazine butanone about 1/10 of the neuroleptic effect of azaperone.

In pigs, azaperone is eliminated 70 - 90 % via the kidneys and 1 - 6 % via the faeces within 48 hours after therapeutic dosages.

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Target species

Pigs

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Indications

A neuroleptic sedative:

1) For the use in animals with aggressive behaviour

- following re-grouping

- in sows (devouring of piglets)

2) For the use in animals with stress and prevention of stress

- cardiovascular stress

- transport-related stress

3) Obstetrics

4) Premedication for local or general anaesthesia

5) For relief of symptoms in animals with nutritional muscular dystrophy.

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Dosage

For intramuscular use.

Administer strictly by intramuscular injection, behind the ear. A long hypodermic needle should be used and the injection given as closely behind the ear as possible and perpendicular to the skin. There is a risk of injecting part of the drug into the fat, if heavy animals are injected with a short needle into the neck. In this case, the injection may have insufficient effect.

Do not administer more than 5 ml per injection site.

Aggressive behaviour (devouring of piglets, re-grouping), obstetrics:

2 mg azaperone/kg body weight, corresponding to 1 ml of the product per 20 kg body weight

Stress:

- cardiovascular stress 0.4 mg azaperone/kg body weight, corresponding to 0.2 ml of the product per 20 kg body weight

- transport-related stress of piglets, weaners, boars 1 mg azaperone/kg body weight, corresponding to 0.5 ml of the product per 20 kg body weight

- transport-related stress of sows and fattening pigs 0.4 mg azaperone/kg body weight, corresponding to 0.2 ml of the product per 20 kg body weight

Premedication for local or general anaesthesia, nutritional muscular dystrophy: 1-2 mg azaperone/kg body weight, corresponding to 0.5-1 ml of the product per 20 kg body weight

A dose of 1 mg/kg should not be exceeded in boars as a higher dose may cause the penis to be extruded, which may then be damaged.

The product is injected once-only behind the ear.

After treatment the animal should be left alone in a quiet environment.

An appropriately graduated syringe must be used to allow accurate administration of the required dose volume. This is particularly important when injecting small volumes.

The rubber stopper may be safely punctured up to 50 times. For multiple vial entry, an aspirating needle or multi-dose syringe is recommended to avoid excessive broaching of the stopper.

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Contraindications

Do not use in very cold conditions as cardiovascular collapse and hypothermia (increased by inhibition of hypothalamic heat regulation centre) due to peripheral vasodilation may occur.

The veterinary medicinal product is contraindicated for use in transport or for re- grouping of pigs which will be slaughtered prior to the end of the withdrawal period.

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

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Adverse reactions

Pigs:

Undetermined frequency: Increased salivation*, tremor*, panting* Reversible penile prolapse in boars

*(at high doses). These side effects disappear spontaneously and leave no lasting damage.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder <or its local representative> or the national competent authority via the national reporting system. See also the last section of the package leaflet for respective contact details.

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Warnings

i) Special precautions for use in animals

Occasional deaths have been observed in Vietnamese Pot Bellied pigs. It is thought this may be caused by injection into the fat leading to slow induction and tendency to use additional doses, leading to overdosage. It is important with this breed not to exceed the stated dose.

If the initial dose does not appear to have an effect, allow complete recovery before re-injecting on a different day.

ii)Special precautions to be taken by the person administering the veterinarymedicinal product to animals

Azaperone, sodium metabisulfite, and methyl and propyl parahydroxybenzoate can cause hypersensitivity reactions. People with known hypersensitivity to azaperone or any of the excipients should avoid contact with the product.

This product may be irritant to the skin, eyes and oral mucosa. Avoid contact with the skin, eyes and oral mucosa. Wash any splashes from skin, eyes and oral mucosa immediately with plenty of water. Seek medical advice if irritation persists. Accidental self-injection or ingestion may result in sedation. Care should be taken to avoid accidental self-injection. Only carry this veterinary medicinal product in an unarmed syringe to avoid accidental injection. In case of accidental self-injection seek medical advice immediately and show the package leaflet or the label to the physician. DO NOT DRIVE.

The veterinary medicinal product should not be administered by pregnant women. No data is available on the presence of azaperone in the milk of breastfeeding women. Breastfeeding women should handle the veterinary medicinal product with extreme caution.

Wash hands after use.

iii) Other precautions

Not applicable.

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Use during pregnancy, lactation or lay

The product can be used in pregnant and lactating animals.

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Interactions

- Azaperone has a potentiating effect on all centrally suppressive substances and hypotensive substances (due to peripheral α-adrenolysis).

- Amplification of tachycardia caused by adrenolytic agents.

- Simultaneous use with α- and β-sympathomimetic substances such as epinephrine (adrenaline) results in hypotension (“adrenaline reversal”).

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Overdose

Aggressive behaviour may occur during awakening in case of overdose.

Repeat dosing in Vietnamese Pot Bellied pigs may result in death due to absorption of the initial dose in fat.

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Special warnings

During onset of action treated animals should be left alone in a quiet environment. Insufficient results may be obtained if the animals are disturbed or chased during the induction period.

Injection into adipose tissue may lead to apparent insufficient effect.

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Withdrawal period

Meat and offal: 18 days.

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Incompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

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Immediate packaging

Clear glass bottle type II sealed with a siliconised bromobutyl rubber stopper and a bordered aluminium-plastic cap.

Package size: Cardboard box with 1 x 100 ml

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Storage

Keep the bottle in the outer carton in order to protect from light.

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years. Shelf life after first opening the immediate packaging: 28 days.

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Disposal of unused product

Medicines should not be disposed of via wastewater.

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

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Additional information

Vm 20631/5000

9 DATE OF FIRST AUTHORISATION

10 March 2021

10 DATE OF REVISION OF THE TEXT

March 2023

11 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product subject to prescription.

Approved: 08 March 2023

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Registration holder

Serumwerk Bernburg AG

Hallesche Landstrasse 105B

06406 Bernburg

Germany

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