SUMMARY OF PRODUCT CHARACTERISTICS

1. Name of the veterinary medicinal product

Sedaxylan

20 mg/ml solution for injection for dogs, cats, horses and cattle

2. Qualitative and quantitative composition

1 millilitre contains:

Active substance:

Xylazine (base) 20.0 mg

Equivalent to 23.32 mg xylazine hydrochloride

Excipients:

Methyl parahydroxybenzoate (E 218) 1.0 mg

Propyl parahydroxybenzoate 0.1 mg

For the full list of excipients, see section 6.1.

3 Pharmaceutical form

Solution for injection

Clear and colourless.

4. Clinical particulars

4.1 Target species

Dogs, cats, horses and cattle.

4.2 Indication for use, specifying the target species

Sedation of dogs, cats, horses and cattle.

4.3 Contraindications

Do not use in the later stages of pregnancy, see section 4.7

Do not use in animals with oesophageal obstruction, and torsion of the stomach, as the muscle relaxant properties of the drug appear to accentuate the effects of the obstruction and because of possible vomiting.

Do not use in animals with renal or hepatic impairment, respiratory dysfunction, cardiac abnormalities, hypotension and/or shock. Do not use in diabetic animals.

Do not use in calves younger than 1 week of age, foals younger than 2 weeks or in puppies and kittens younger than 6 weeks. See also section 4.7.

4.4 Special warnings for each target species

Dogs and cats:

Horses:

• Xylazine inhibits the normal intestinal motility. Therefore, it should only be used in horses with colic, that are not responsive to analgesics. The use of xylazine should be avoided in horses with caecal malfunction. .

• After treatment of horses with xylazine, the animals are reluctant to walk, so whenever possible the drug should be administered in the place where the treatment/investigation is going to take place.

• Caution should be taken in the administration of the product to horses susceptible to laminitis.

• Horses with air way disease or malfunction may develop life-threatening dyspnoea.

• The dose should be kept as low as possible.

Cattle:

• Ruminants are highly susceptible to the effects of xylazine. Normally cattle remain standing at the lower doses, but some animals may lie down. At the highest recommended doses most animals will lie down and some animals may relapse in lateral recumbency.

• Reticulo-ruminal motor functions are depressed after injection of xylazine. This may results in bloat. It is advisable to withhold feed and water for several hours before administration of xylazine.

• In cattle the ability to eructate, cough and swallow is retained but reduced during the period of sedation, therefore cattle must be closely watched during the recovery period: the animals should be maintained in sternal recumbency.

4.5 Special precautions for use

Special precautions for use in animals

• Older and exhausted animals are more sensitive to xylazine, whilst nervous or highly excitable animals may require a relatively high dose.

• In case of dehydration, xylazine should be used cautiously.

• Emesis is generally seen within 3-5 minutes after xylazine administration in cats and dogs. It is advisable to fast dogs and cats for 12 hours prior to surgery; they may have free access to drinking water.

• Do not exceed the recommended dosage.

• Following administration animals should be allowed to rest quietly until the full effect has been reached.

• It is advised to cool animals when the ambient temperature is above 25°C and to keep animals warm at low temperatures. .

• Because the analgesic properties of xylazine are insufficient, in painful procedures xylazine should always be used in combination with a local or general analgesic!

• Xylazine produces a certain degree of ataxia; therefore, xylazine must be used cautiously in procedures involving the distal extremities and in standing castrations in the horse.

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

• Irritation, sensitisation, contact dermatitis and systemic effects cannot be excluded after skin contact.

• Avoid skin contact and wear impermeable gloves when handling the product.

• Wash the exposed skin immediately after exposure with large amounts of water.

• In the case of accidental projection of the product into the eyes, rinse abundantly with fresh water. If irritation persists, seek the advice of a physician.

• Remove contaminated clothes.

• Pregnant women should not handle the product.

• Advice to doctors: Xylazine is an -adrenoreceptor agonist whose toxicity may cause clinical effects including sedation, respiratory depression and coma, bradycardia and hypotension and hyperglycaemia. Ventricular arrhythmias have also been reported. Treatment should be supportive with appropriate intensive therapy.

4.6 Adverse reactions (frequency and seriousness)

In general, side effects, typical for an α2-adrenergic agonist, like bradycardia, reversible arrhythmia and hypotension can occur. Thermoregulation can be influenced and consequently body temperature can decrease or increase dependant on the ambient temperature. Depression of respiration and / or respiratory arrest can occur, especially in cats.

Dogs and cats

• Dogs and cats frequently vomit during the onset of the xylazine-induced sedation, especially when the animals have just been fed.

• Animals may show profound salivation following an injection with xylazine.

• Other adverse effects for dogs and cats include: muscle tremors, bradycardia with AV-block, hypotension, reduced respiratory rate, movement in response to strong auditory stimuli, and increased urination in cats.

• In cats xylazine causes uterine contractions and it may induce premature parturition.

Horses

• Horses often sweat as the effects of the sedation are wearing off.

• Severe bradycardia and reduced respiratory rate have been reported especially in horses.

• Muscle tremors and movement in response to sharp auditory or physical stimuli are possible. Although rare, violent reactions have been reported in horses following the administration of xylazine.

• Ataxia and reversible prolapse of the penis may occur.

Cattle

• In cattle xylazine may induce premature parturition, and it also reduces implantation of the ovum.

• Cattle, which have received high doses of xylazine sometimes suffer from loose faeces for 24 hours afterwards.

• Other adverse reactions include profound salivation, ruminal atony, atony of the tongue, regurgitation, bloating, hypothermia, bradycardia, increased urination and reversible prolapse of the penis.

• In cattle, adverse effects are generally more pronounced after intramuscular administration compared to intravenous

4.7 Use during pregnancy and lactation

Although laboratory studies in rats have not shown any evidence of teratogenic or foetotoxic effects the use of the product during the first two trimesters of pregnancy should only be made according to the benefit/risk assessment by the responsible veterinarian.

Do not use in the later stages of pregnancy (particularly in cattle and cats), because xylazine causes uterine contractions and it may induce premature labour.

Do not use in cattle receiving ovum transplants as the increased uterine tone may reduce the chance of implantation of the ovum.

4.8 Interaction with other medicinal products and other forms of interaction

Other CNS depressant agents (barbiturates, narcotics, anaesthetics, tranquillizers, etc.) may cause additive CNS depression if used with xylazine. Dosages of these agents may need to be reduced. Xylazine should therefore be used cautiously in combination with neuroleptics or tranquillizers.

Xylazine should not be used in combination with sympathomimetic drugs such as epinephrine as ventricular arrhythmia may follow.

4.9 Amounts to be administered and administration route

This product is intended for single intravenous, intramuscular or subcutaneous injection dependent upon the species in which it is to be used. The individual response to xylazine is somewhat varied (as with other sedatives), and depends partly on the dosage, the age of the patient, temperament of the patient, the surroundings (stress) and general condition (diseases, fat percentage, etc.). Doses also depend on the desired degree of sedation. Generally time to onset of sedation and recovery will take longer after intramuscular or subcutaneous injection at the recommended dosages than after intravenous injection. First effects are usually seen within 2 minutes following intravenous injection and within 5 to 10 minutes after intramuscular or subcutaneous injection. The maximum effect is seen 10 minutes later. It is generally seen that an increase in dose will lead to an increase in the level of sedation, until a maximum level is attained. Increasing the dosage beyond this point will lead to increase of the duration of the sedation. Recovery in calves may be prolonged after administration of 1.5 x the recommended dose. If the required depth of sedation is not achieved it is unlikely that repetition of the dose will prove more effective. In that case it is advisable to allow complete recovery repeating the procedure with a higher dose after 24 hours.

Accurately ascertain the body weight of an animal before treatment with xylazine. Use a syringe with appropriate gradations.

Dogs:	1.0 - 2.0	mg per kg body weight intramuscularly or subcutaneously
	0.5 – 1.0	ml injection solution/10 kg body weight IM or SC
	0.7 - 1.0	mg per kg body weight intravenously.
	0.35 – 0.5	ml injection solution/10 kg body weight IV
Cats:	0.5 - 1.0	mg per kg body weight intramuscularly or subcutaneously.
	0.125 – 0.25	ml injection solution/ 5 kg body weight IM or SC
Horses:	0.5 - 1.0	mg per kg body weight intravenously.
	2.5 – 5.0	ml injection solution/100 kg body weight IV
Cattle:	0.05 – 0.20	mg per kg body weight intramuscularly or
	0.25 – 1.0	ml injection solution/100 kg body weight IM
	0.03 – 0.10	mg per kg body weight intravenously.
	0.15 – 0.5	ml injection solution/100 kg body weight IV

The intravenous injection should be given slowly, especially in horses.

4.10 Overdose (symptoms, emergency procedures, antidotes)

In the event of an accidental overdose, cardiac arrhythmias, hypotension, and profound CNS and respiratory depression may occur. Seizures have also been reported after an overdose. Xylazine can be antagonized by ₂-adrenergic antagonists: atipamezole has been found to be a useful antidote in some cases. The recommended dosage is: 0.2 mg/kg for dogs and cats.

To treat the respiratory depressant effects of xylazine, mechanically respiratory support with or without respiratory stimulants (e.g. doxapram) can be recommended.

4.11 Withdrawal periods

Horse (meat and offal): 1 day.

Cattle (meat and offal ): 1 day.

Cattle (milk): Zero days.

5. Pharmacological properties

Pharmacotherapeutic group: Psycholeptics, Hypnotics and sedatives.

ATC Vet Code : QN05CM92

5.1 Pharmacodynamic properties

Xylazine belongs to the ₂-adrenoceptor agonists.

Xylazine is a ₂-adrenoceptor agonist, that acts by stimulation of central and peripheral ₂-adrenoceptors.. Through its central stimulation of ₂-adrenoceptors, xylazine has potent antinociceptive activity. In addition ₂-adrenergic activity, xylazine has ₁-adrenergic effects. Xylazine also produces skeletal muscle relaxation by inhibition of intraneuronal transmission of impulses at the central level of the central nervous system. The analgesic and skeletal muscle relaxation properties of xylazine show considerable interspecies variations. Sufficient analgesia generally will be attained in combination with other products only.

In many species, administration of xylazine produces a short-lived arterial pressor effect followed by a longer period of hypotension and bradycardia. These contrasting actions upon the arterial pressure apparently are related to the ₂- an ₁-adrenergic actions of xylazine.

Xylazine has several endocrine effects. Insulin (mediated by ₂-receptors in pancreatic -cells which inhibit insulin release), ADH (decreased production of ADH, causing polyuria) and FSH (decreased) are reported to be influenced by xylazine.

5.2 Pharmacokinetic particulars

Absorption (and action) is rapid following intramuscular injection. Levels of drug peak rapidly (usually within 15 minutes) and then decline exponentially. Xylazine is a highly lipid soluble organic base and diffuses extensively and rapidly (Vd 1.9-2.7). Within minutes after an intravenous injection, it can be found in a high concentration in the kidneys, the liver, the CNS, the hypophyses, and the diaphragm. So there is a very rapid transfer from the blood vessels to the tissues. Intramuscular bioavailability is incomplete and variable ranging from 52-90% in the dog to 40-48% in the horse. Xylazine is metabolised extensively and eliminated rapidly (+70% via the urine, while the enteric elimination is + 30%). The rapid elimination of xylazine is probably related to an extensive metabolism rather than to a rapid renal excretion of unchanged xylazine.

6. Pharmaceuticals particulars

6.1 List of excipients

Citric acid monohydrate,

Sodium citrate,

Methyl parahydroxybenzoate (E 218),

Propyl parahydroxybenzoate ,

Propylene glycol,

Water for Injections

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: 3 years

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

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

- Vial

* volume 30 ml and 50 ml

* contents 25 ml and 50 ml

* glass type II

* amber coloured

- Stopper

* bromobutyl rubber stopper type I

* secured with aluminium cap

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused 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 AUTHORIZATION HOLDER

Eurovet Animal Health B.V.

Handelsweg 25

5531 AE Bladel

The Netherlands

8. MARKETING AUTHORIZATION NUMBER

Vm 16849/4001

9. DATE OF FIRST AUTHORISATION

Date: July 2003

10. DATE OF REVISION OF THE TEXT

Date: September 2014

16 October 2014