Butador 10 mg/ml Solution for Injection for Horses, Dogs and Cats

Composition

Each ml contains:

Active substance:

Butorphanol 10 mg

(as butorphanol tartrate 14.58 mg)

Excipients:

Clear, colourless to almost colourless solution for injection.

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Pharmacological properties

4.1 ATCvet code: QN02AF01

4.2 Pharmacodynamics

Butorphanol is a centrally acting analgesic from the group of synthetic opioids with an agonistic-antagonistic effect, agonist at the kappa opioid receptor subtype and antagonist at the mu receptor subtype. The kappa receptors control analgesia, sedation without depression of cardiopulmonary system and body temperature, whereas the mu receptors control supraspinal analgesia, sedation and depression of cardiopulmonary system and body temperature.

The agonist component of butorphanol activity is ten times more potent than the antagonist component.

Analgesia generally occurs within 15 minutes following administration in horse, dog and cat. After a single intravenous dose in the horse analgesia usually lasts up to 2 hours. In the dog it lasts up to 30 minutes after a single intravenous administration. In cats with visceral pain analgesic effects have been demonstrated for up to 6 hours. In cats with somatic pain duration of analgesia has been considerably shorter.

Increased doses do not correlate with increased analgesia, a dosage of about 0.4 mg/kg leads to a ceiling effect.

Butorphanol has minimal cardiopulmonary depressant activity in the target species. It does not cause histamine release in horses. In combination with α2-agonists it causes additive and synergistic sedation.

4.3 Pharmacokinetics

Post parenteral administration absorption of the veterinary medicinal product is rapid and almost complete with serum peak levels occurring after 0.5 - 1.5 hours. It is highly bound to plasma proteins (up to 80 %). Metabolism is rapid and mainly occurs in the liver. Two inactive metabolites are produced. The elimination occurs mainly through urine (to a major extent) and faeces.

Horses: Volume of distribution is large after i.v. administration (2.1 l/kg) suggesting wide distribution into tissues. Terminal half life is short: about 44 minutes. 97 % of the dose after i.v. administration in the horse will be eliminated in less than 5 hours.

Dogs: Volume of distribution is large after i.v. administration (4.4 l/kg) suggesting wide distribution into tissues. Terminal half life is short: about 1.7 hours.

Cats: Volume of distribution is large after i.v. administration (7.4 l/kg) suggesting wide distribution into tissues. Terminal half life is short: about 4.1 hours.

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Target species

Horses, dogs, cats

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Indications

Horses

As an analgesic For the short term relief of pain such as colic of gastrointestinal tract origin.

As a sedative and pre-anaesthetic In combination with α2-adrenoceptor agonists (detomidine, romifidine, xylazine): For therapeutic and diagnostic procedures such as minor standing surgery and sedation of intractable patients.

Dogs, cats

As an analgesic

For relief of moderate visceral pain e.g. pre- and post-surgical as well as post-traumatic pain.

As a sedative In combination with α2-adrenoceptor agonists (medetomidine).

As a pre-anaesthetic Part of anaesthetic regime (medetomidine, ketamine).

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Dosage

For intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) use.

Horses: Intravenous

Dogs: Intravenous, subcutaneous or intramuscular

Cats: Intravenous or subcutaneous

To ensure a correct dosage, body weight should be determined as accurately as possible.

Horses

As an analgesic Monotherapy:

0.1 mg/kg (1 ml/100 kg bw) i.v.

As a sedative and as a pre-anaesthetic With detomidine:

Detomidine: 0.012 mg/kg i.v., followed within 5 minutes by Butorphanol: 0.025 mg/kg (0.25 ml /100 kg bw) i.v.

With romifidine:

Romifidine: 0.05 mg/kg i.v., followed within 5 minutes by Butorphanol: 0.02 mg/kg (0.2 ml /100 kg bw) i.v..

With xylazine:

Xylazine: 0.5 mg/kg i.v., followed after 3 - 5 minutes by Butorphanol: 0.05 – 0.1 mg/kg (0.5 - 1 ml /100 kg bw) i.v..

Dogs

As an analgesic Monotherapy:

0.1 - 0.4 mg/kg (0.01 – 0.04 ml/kg bw) slowly i.v. (in the lower to medium dose range) as well as i.m., s.c..

For post-operative pain control the injection should be administered 15 minutes before the end of anaesthesia in order to achieve sufficient pain relief during the recovery phase.

As a sedative With medetomidine:

Butorphanol: 0.1 mg/kg (0.01 ml/kg bw) i.v., i.m.

Medetomidine: 0.01 mg/kg i.v., i.m.

As a pre-anaesthetic With medetomidine and ketamine:

Butorphanol: 0.1 mg/kg (0.01 ml/kg bw) i.m.

Medetomidine: 0.025 mg/kg i.m., followed after 15 minutes by Ketamine: 5 mg/kg i.m.

It is only possible to use atipamezole 0.1 mg/kg body weight for medetomidine- antagonisation when ketamine action has ceased.

Cats

As an analgesic Monotherapy:

15 minutes prior to recovery either: 0.4 mg/kg (0.04 ml/kg bw) s.c. or: 0.1 mg/kg (0.01 ml/kg bw) i.v.

As a sedative With medetomidine:

Butorphanol: 0.4 mg/kg (0.04 ml/ kg bw) s.c.

Medetomidine: 0.05 mg/kg s.c.

For wound debridement an additional local anaesthesia is recommended.

Medetomidine-antagonisation is possible with atipamezole 0.125 mg/kg body weight.

As a pre-anaesthetic With medetomidine and ketamine:

Butorphanol: 0.1 mg/kg (0.01 ml/ kg bw) i.v.

Medetomidine: 0.04 mg/kg i.v.

Ketamine: 1.5 mg/kg i.v.

It is only possible to use atipamezole 0.1 mg/kg body weight for medetomidine– antagonisation when ketamine action has ceased.

Butorphanol is intended for use where short (horses and dogs) and short to medium (cats) analgesia is required. The dose may be repeated as required. The need for and timing of repeated treatment will be based on clinical response. For information on the duration of analgesia see section 4.2.

Rapid intravenous injection should be avoided.

The stopper must not be punctured more than 25 times.

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Contraindications

Do not use in cases of hypersensitivity to the active substance or to any of the excipients. Do not use for treatment of animals with severe dysfunction of the liver and kidneys, in case of cerebral injury or organic brain lesions and in animals with obstructive respiratory diseases, heart dysfunctions or spastic conditions.

For combination use with α2-agonists in horses:

Do not use in horses with a pre-existing cardiac dysrhythmia or bradycardia. Do not use in cases of colic associated with impaction, as the combination will cause a reduction in gastrointestinal motility.

Do not use combination during pregnancy.

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Adverse reactions

Horses:

Very common (>1 animal / 10 animals treated): Ataxia1, Sedation2.

Undetermined frequency (cannot be estimated from the available data): Involuntary movement3; Digestive tract hypomotility4; Respiratory depression5; Cardiac depression.

1 Lasting about 3 to 15 minutes.

2 Mild.

3 Running movements.

4 Mild and transient. Any reduction of gastrointestinal motility caused by butorphanol may be enhanced by the concomitant use of α2-agonists.

5 The respiratory depressive effects of α2-agonists may be enhanced by concomitant butorphanol, particularly if respiratory function is already impaired.

Dogs:

Rare (1 to 10 animals / 10,000 animals treated): Ataxia; Anorexia; Diarrhoea.

Undetermined frequency (cannot be estimated from the available data): Respiratory depression; Cardiac depression; Injection site pain1; Digestive tract hypomotility.

1 Associated with intramuscular administration.

Cats:

Rare (1 to 10 animals / 10,000 animals treated): Ataxia; Anorexia; Diarrhoea.

Undetermined frequency (cannot be estimated from the available data): Respiratory depression; Cardiac depression; Injection site pain1; Digestive tract hypomotility; Excitation, Anxiety; Sedation, Mydriasis, Disorientation; Dysphoria.

1 Associated with intramuscular administration.

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 the package leaflet for respective contact details.

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Warnings

Special precautions for safe use in the target species:

The safety of the veterinary medicinal product in puppies, kitten and foals has not been established. Use of the veterinary medicinal product in these groups should be on the basis of a risk-benefit analysis by the responsible veterinarian.

Due to its antitussive properties, butorphanol may lead to an accumulation of mucous in the respiratory tract. Therefore, in animals with respiratory diseases associated with increased mucous production, butorphanol should only be used after a risk-benefit evaluation by the responsible veterinarian. If respiratory depression occurs, naloxone may be used as an antidote.

Sedation may be noted in treated animals. The combination of butorphanol and α2-adrenoceptor agonists should be used with caution in animals with cardiovascular disease. The concurrent use of anticholinergic drugs, e.g. atropine should be considered. Routine cardiac auscultation should be performed prior to use in combination with α2-adrenoceptor agonists.

Administration of butorphanol and romifidine in one syringe should be avoided due to increased bradycardia, heart block and ataxia.

Horses

The use of the veterinary medicinal product at the recommended dose may lead to transient ataxia and/or excitement. Therefore, to prevent injuries in patient and people when treating horses, the location for the treatment should be chosen carefully.

Dogs

In dogs with MDR1 mutation reduce dose by 25 - 50 %.

Cats

Cats should be weighed to ensure that the correct dose is calculated. An appropriate graduated syringe must be used to allow accurate administration of the required dose volume (e.g. insulin syringe or 1 ml graduated syringe). If repeated administrations are required, use different injection sites.

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

Butorphanol has opioid-like activity. Precautions should be taken to avoid accidental injection/self-injection with this potent drug. The most frequent adverse effects of butorphanol in humans are drowsiness, sweating, nausea, dizziness and vertigo and may occur following unintended self-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. An opioid antagonist (e.g. naloxone) may be used as an antidote. Wash splashes from skin and eyes immediately.

Special precautions for the protection of the environment:

Not applicable.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

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Use during pregnancy, lactation or lay

Pregnancy and lactation:

Butorphanol crosses the placental barrier and penetrates into milk. Studies in laboratory species have not produced any evidence of teratogenic effects.

The safety of the veterinary medicinal product has not been established in the target species during pregnancy and lactation. The use of butorphanol is not recommended during pregnancy and lactation.

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Interactions

The concomitant administration of other drugs which are metabolised in the liver may enhance the effect of butorphanol.

Butorphanol used with concurrently administered anaesthetics, centrally sedative or respiratory depressive drugs produces additive effects. Any use of butorphanol in this context requires acute control and a careful adaptation of the dose.

Administration of butorphanol may remove the analgesic effect in animals, which have already received pure μ-opioid analgesics.

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Overdose

Horses

Increased dosages could result in respiratory depression as a general opioid effect. Intravenous doses of 1.0 mg/kg (10 x the recommended dose), repeated at 4-hourly intervals for 2 days, led to transient adverse effects, including pyrexia, tachypnoea, CNS signs (hyperexcitability, restlessness, mild ataxia leading to somnolence) and gastrointestinal hypomotility, sometimes with abdominal discomfort. An opioid antagonist (e.g. Naloxone) may be used as an antidote.

Dogs, cats

Miosis (dog)/Mydriasis (cat), respiratory depression, hypotension, disorders of the cardiovascular system and in severe cases respiratory inhibition, shock and coma. Depending on the clinical situation counter-measures should be taken under intense medical monitoring. Monitoring is required for a minimum of 24 hours.

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Special warnings

The precautionary measures required for contact with animals should be followed and stress factors for the animals should be avoided.

In cats, individual response to butorphanol may be variable. In the absence of an adequate analgesic response, an alternative analgesic agent should be used.

Increasing of the dose may not increase the intensity or duration of analgesia.

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Withdrawal period

Horses

Meat and offal: zero days

Milk: zero hours

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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 type I vials with bromobutyl rubber stoppers and aluminium caps. Package sizes: 1 x 10 ml, 5 x 10 ml, 10 x 10 ml, 1 x 50 ml.

Not all pack sizes may be marketed.

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Storage

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

Keep the vial 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.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

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Additional information

GB: Vm 57446/5006

NI: Vm 57446/3006

8 DATE OF FIRST AUTHORISATION

17 January 2011

9 DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

July 2024

10 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCT

Veterinary medicinal product subject to prescription.

Find more product information by searching for the ‘Product Information Database’ on www.gov.uk.

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Registration holder

VetViva Richter GmbH

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