Anaestamine 100 mg/ml Solution for Injection

Composition

Each ml contains:

Active substance:

Ketamine 100 mg

(equivalent to 115.34 mg ketamine hydrochloride)

Excipient(s):

Chlorocresol 1 mg

For the full list of excipients, see section 6.1.

6.1 List of excipients

Chlorocresol

Sodium hydroxide (for pH adjustment)

Water for injections

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Pharmaceutical form

Solution for injection

Clear, colourless aqueous solution.

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Pharmacological properties

Pharmacotherapeutic group: anaesthetics, other general anaesthetics, ketamine

ATC vet code: QN01AX03.

5.1 Pharmacodynamic properties

Ketamine is a dissociative anaesthetic agent. Ketamine induces a state of catalepsy with amnesia and analgesia; muscle tone is maintained including the pharyngeal and laryngeal reflexes. The heart rate, blood pressure and cardiac output are increased; respiratory depression is not a noticeable feature. All these characteristics may be modified if the product is used in combination with other agents.

5.2 Pharmacokinetic particulars

Ketamine is distributed rapidly. Distribution to tissues is variable with highest concentrations found in the liver and kidneys. Plasma protein binding is approximately 50%. Hepatic metabolism varies between species: for example, ketamine undergoes extensive hepatic biotransformation in dogs and horses, but the majority of the drug is excreted via the kidneys in cats. Recovery from ketamine anaesthesia after an intravenous bolus occurs by rapid redistribution from the CNS to other tissues, primarily fat, lung, liver and kidney

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Target species

Dogs, cats, cattle, sheep, goats, horses, pigs, guinea pigs, hamsters, rabbits, rats, mice.

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Indications

The product may be used in combination with a sedative for:

- Immobilisation

- Sedation

- General anaesthesia

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Dosage

For intravenous and intramuscular use.

In laboratory animals, intraperitoneal use is also possible. Ketamine should be combined with a sedative.

One dose of 10 mg of ketamine per kg bodyweight corresponds to 0.1 ml of a 100 mg/ml solution per kg bodyweight.

Ketamine can show large inter-individual variation in effect, and therefore dose rates administered should be tailored to the individual animal, dependent on factors such as age, condition, and the depth and duration of anaesthesia required.

Before ketamine is administered, please ensure that the animals are adequately sedated.

DOG

Combination with xylazine or medetomidine

Xylazine (1.1 mg/kg IM) or medetomidine (10 to 30 µg/kg IM) can be used with Ketamine (5 to 10 mg/kg i.e. 0.5 to 1 ml/10 kg IM) for short term anesthesia of 25 to 40 min. The ketamine dose can be adjusted, depending on the desired duration of surgery.

CAT

Combination with xylazine

Xylazine (0.5 to 1.1 mg/kg IM) with or without atropine is administered 20 min before ketamine (11 to 22 mg/kg IM i.e. 0.11 to 0.22 ml/kg IM).

Combination with medetomidine

Medetomidine (10 to 80 µg/kg IM) can be combined with ketamine (2.5 to 7.5 mg/kg IM i.e 0.025 to 0.075ml/kg IM). The dose of ketamine should be reduced as the dose of medetomidine increases.

HORSE

Combination with detomidine:

Detomidine 20 µg/kg IV, after 5 minutes ketamine 2.2 mg/kg fast IV (2.2 ml/100 kg IV)

Onset of action is gradual, taking approximately 1 minute to attain recumbency, with duration of anaesthetic effect lasting approximately 10 - 15 minutes.

Combination with xylazine:

Xylazine 1.1 mg/kg IV, followed by ketamine 2.2 mg/kg IV (2.2 ml/100 kg IV)

Onset of action is gradual, taking approximately 1 minute, with duration of anaesthetic effect being variable and lasting 10 - 30 minutes but usually less than 20 minutes.

After injection the horse lays down spontaneously without any further help. If a distinct muscle relaxation is required simultaneously, muscle relaxants can be administered to the recumbent animal, until the horse shows first symptoms of relaxation.

CATTLE

Combination with xylazine:

Adult cattle can be anesthetized for short periods with xylazine (0.1 to 0.2 mg/kg IV) followed by ketamine (2 mg/kg IV i.e. 2 ml/100kg IV). The lower dose of xylazine is used when cattle weigh more than 600 kg. Anesthesia Iasts approximately 30 min but can be pro-longed for 15 min with additional ketamine (0.75 to 1.25 mg/kg IV i.e. 0.75 to 1.25 ml/100kg IV).

SHEEP

Ketamine 7.5 to 22 mg/kg IV i.e. 0.75 to 2.2 ml/10kg IV depending on the sedative used.

GOAT

Ketamine 11 to 22 mg/kg IM i.e. 1.1 to 2.2 ml/10kg IM depending on the sedative used.

PIG

Combination with azaperone:

Ketamine 15 - 20 mg/kg IM (1.5 - 2 ml/10 kg) and 2 mg/kg azaperone IM.

In 4 – 5 month old pigs, following administration of 2 mg/kg azaperone and 20 mg/kg ketamine IM, the onset of anaesthesia took on average 29 minutes and duration of effect lasted about 27 minutes.

LABORATORY ANIMALS

Combination with xylazine

Rabbits: xylazine (5-10 mg/kg IM) + ketamine (35-50 mg/kg IM i.e. 0.35 to 0.50 ml/kg IM)

Rats: xylazine (5-10 mg/kg IP, IM) + ketamine (40-80 mg/kg IP, IM i.e. 0.4-0.8 ml/kg IP, IM)

Mice: xylazine (7.5-16 mg/kg IP) + ketamine (90-100 mg/kg IP i.e. 0.9 to 1.0 ml/kg IP)

Guinea pigs: xylazine (0.1 to 5 mg/kg IM) + ketamine (30-80 mg/kg IM i.e. 0.3 to 0.8 ml/kg IM)

Hamster: xylazine (5 to 10 mg/kg IP) + ketamine (50 to 200 mg/kg IP i.e. 0.5 to 2 ml/kg IP)

Dose for maintenance of anaesthesia:

When needed prolongation of effect is possible by repeated administration of an optionally reduced initial dose.

The vial can be broached up to 20 times. The user should choose the most appropriate vial size according to the target species to be treated and the administration route.

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Contraindications

Do not use in animals presenting with:

- severe hypertension,

- cardio-respiratory deficiency,

- hepatic or renal dysfunction.

Do not use in animals with glaucoma.

Do not use in animals with eclampsia or pre-eclampsia.

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

Do not use the product as a sole anaesthetic agent in any of the target species.

Do not use for surgical intervention on pharynx, larynx, trachea or bronchial tree, if sufficient relaxation is not ensured by administration of a muscle relaxant (intubation obligatory).

Do not use in ocular surgical interventions.

Do not use in animals undergoing a myelogram procedure.

Do not use in patients with pheochromocytoma or untreated hyperthyroidism.

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Adverse reactions

Emergence reactions - ataxia, hypersensitivity to stimuli, excitation – have been reported in horses and dogs rarely and very rarely respectively.

Salivation in cats has been reported very rarely.

Increased tonus of skeletal muscles in cats, dogs, horses, rabbits, cattle and goats has been reported very rarely.

Dose-related respiratory depression, which may lead to respiratory arrest in cats, dogs, rabbits, cattle and goats has been reported very rarely Combination with respiratory depressant products may increase this respiratory effect.

Increased heart rate in cats and dogs has been reported very rarely.

Increased arterial blood pressure with concurrent increased bleeding tendency in dogs has been reported very rarely.

Eyes that remain open with mydriasis and nystagmus have been reported in cats very rarely.

Pain on intramuscular injection in cats has been reported very rarely.

All adverse reactions and frequencies are from spontaneous reports.

The frequency of adverse reactions is defined using the following convention:

- very common (more than 1 in 10 animals treated displaying adverse reaction(s))

- common (more than 1 but less than 10 animals in 100 animals treated)

- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

- rare (more than 1 but less than 10 animals in 10,000 animals treated)

- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).>

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Warnings

Special precautions for use in animals

A small proportion of animals have been reported to be unresponsive to ketamine as an anaesthetic agent at normal dosages. Use of premedicants should be followed by a suitable reduction in dosage.

In the cat and dog, the eyes remain open and the pupils dilated. The eyes may be protected by covering with a damp gauze swab or using appropriate ointments. Ketamine may exhibit pro-convulsant and anti-convulsant properties, and therefore should be used with care in patients with seizure disorders.

Ketamine may increase intracranial pressure and therefore, may not be suitable for patients with cerebrovascular insults.

When used in combination with other products, consult the contraindications and warnings that appear on the relevant data sheets.

The eyelid reflex stays intact.

Twitching, as well as excitation upon recovery, may be possible. It is important that both premedication and recovery should occur in quiet and calm surroundings. To ensure a smooth recovery appropriate analgesia and premedication should be administered, if indicated.

The concomitant use of other pre-anaesthetics or anaesthetics should be subject to a benefit/risk assessment, taking into account the composition of the used medicines and their doses and the nature of the intervention. The recommended doses of ketamine are likely to vary depending on the concomitant pre-anaesthetics and anaesthetics used.

The prior administration of an anticholinergic such as atropine or glycopyrrolate to prevent the occurrence of adverse effects, especially hypersalivation, may be considered after a benefit/risk assessment by the veterinarian.

Ketamine should be used with caution when pulmonary disease is present or suspected.

In small rodents cooling down should be prevented.

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

This is a potent drug. Particular care should be taken to avoid accidental self-administration.

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

Avoid contact with the skin and eyes. Wash any splashes from skin and eyes immediately with large amounts of water.

Adverse effects on the foetus cannot be excluded. Pregnant women should avoid handling the product.

In case of accidental self-injection or if symptoms occur after ocular/oral contact, seek medical advice immediately and show the package leaflet or the label to the physician, but DO NOT DRIVE.

To the physician:Do not leave patient unattended. Maintain airways and give symptomatic and supportive treatment.

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Use during pregnancy, lactation or lay

Ketamine passes the blood placenta barrier very well to enter the fetal blood circulation in which 75 to 100 % of the maternal blood levels can be reached. This partially anesthetizes neonates delivered by caesarean section. The safety of the veterinary medicinal product has not been established during pregnancy and lactation. Use only accordingly to the benefit/risk assessment by the responsible veterinarian.

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Interactions

Neuroleptics, tranquillisers, cimetidine and chloramphenicol potentiate ketamine anaesthesia (also seesection 4.4).

Barbiturates, opiates and diazepam may prolong the recovery time.

Effects may be potentiated. A decrease of the dose of one or both agents may be necessary.

There is a possibility of an increased risk of cardiac arrhythmia when ketamine is used in combination with thiopental or halothane. Halothane prolongs the half-life of ketamine.

The simultaneous intravenous administration of a spasmolytic agent may provoke a collapse.

Theophylline, when given with ketamine, may provoke an increase of epileptic crises.

When detomidine is used together with ketamine, the recovery is slower than when ketamine is used alone.

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Overdose

In case of overdose cardiac arrhythmia and respiratory depression up to paralysis may occur. If necessary, suitable artificial aids to maintain ventilation and cardiac output should be used until sufficient detoxification has taken place. Pharmacological cardiac stimulants are not recommended, unless no other supportive measures are available.

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Special warnings

For very painful and major surgical interventions, as well as for maintenance of anaesthesia, a combination with injectable or inhalation anaesthetics is necessary. As muscle relaxation required for surgical procedures cannot be achieved with ketamine alone, additional muscle-relaxants should be used concomitantly. For improvement of anaesthesia or prolongation of effect ketamine can be combined with α2-receptor- agonists, anaesthetics, neuroleptanalgesics, tranquilizers and inhalational anaesthetic agents.

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Withdrawal period

Cattle, sheep, goats and horses:

Meat and offal : 1 day.

Milk : zero days.

Pigs :

Meat and offal : 1 day.

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Incompatibilities

Due to a chemical incompatibility, do not mix barbiturates or diazepam with ketamine in the same syringe.

The product must not be mixed with other veterinary medicinal products, with the exception of the infusion fluids 0.9% sodium chloride, Ringers solution and lactated Ringers solution.

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Immediate packaging

Clear type I glass vials containing 10 ml, 25 ml and 50 ml product, closed with a bromobutyl rubber stopper and aluminium cap in a carton box.. Not all pack sizes may be marketed.

Not all pack sizes may be marketed.

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Storage

Store the vial in the original packaging in order to protect from light. Store the vial upright.

This veterinary medicinal product does not require any special temperature storage conditions’

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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

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

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Additional information

Vm 41821/4011

9 DATE OF FIRST AUTHORISATION

21 October 2014

10 DATE OF REVISION OF THE TEXT

August 2019

Approved: 02 August 2019

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Registration holder

Le Vet Beheer B.V.

Wilgenweg 7

3421 TV Oudewater

The Netherlands

Tel: +31-(0)348-565858

Fax: +31-(0)348-565454

E-mail: [email protected]

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