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Date: Friday, November 27, 2020 23:00

Description: MSD-AH
Release 3.21
Dolorex 10 mg/ml Solution for Injection for horse, dog and cat
 
Species: Cats, Dogs, Horses and other equidae
Therapeutic indication: Pharmaceuticals: Neurological preparations: Analgesics
Active ingredient: Butorphanol Tartrate
Product:Dolorex® 10 mg/ml Solution for Injection for horse, dog and cat
Product index: Dolorex
Withdrawal notes: Horse: Meat and offal - Zero days. Milk - Zero days
Qualitative and quantitative composition
Each ml contains:
Active substance:
Butorphanol 10 mg (equivalent to butorphanol tartrate 14.6 mg).
Excipients:
Benzethonium chloride 0.1 mg.
For the full list of excipients, see section ‘Pharmaceutical Particulars’.
Pharmaceutical form
Solution for injection. Aqueous colourless solution.
Clinical particulars
Target Species:
Horse, dog and cat.
Indications for use:
Butorphanol is intended for use where short (horse and dog) and short to medium (cat) duration analgesia is required.
For information on the duration of analgesia that can be expected following treatment, see section ‘Pharmacological particulars’.
Horse:
For relief of pain associated with colic of gastrointestinal tract origin.
For sedation in combination with certain α2-adrenoceptor agonists (see section ‘Amounts to be administered’).
Dog:
For relief of moderate visceral pain.
For sedation in combination with certain α2-adrenoceptor agonists (see section ‘Amounts to be administered’).
Cat:
For the relief of moderate pain associated with soft tissue surgery.
Contra-indications:
Do not use in animals with a history of liver or kidney disease.
Do not use in cases of hypersensitivity to the active ingredient or to any of the excipients.
Butorphanol/detomidine combination:
The combination should not be used in horses with a pre-existing cardiac dysrhythmia or bradycardia.
The combination will cause a reduction in gastrointestinal motility and consequently should not be used in cases of colic associated with impaction.
Special warnings for each target species:
In cats, individual response to butorphanol may be variable. In the absence of an adequate analgesic response, an alternative analgesic agent should be used (see section ‘Amounts to be administered’). Increasing of the dose may not increase the intensity or duration of analgesia.
Special precautions for use:
Butorphanol is a morphinan derivative and therefore possesses opioid activity.
Horse:
The use of the 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.
Horse, dog, and cat:
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 or in animals that are being treated with expectorants, butorphanol should only be used on the basis of a risk-benefit analysis by the responsible veterinarian.
The concomitant use of other central nervous depressants would be expected to potentiate the effects of butorphanol and such drugs should be used with caution. A reduced dose should be used when administering these agents concurrently.
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.
The safety of the product in young puppies, kittens and foals has not been established. Use of the product in these groups should be on the basis of a risk: benefit analysis by the responsible veterinarian.
Operator warnings:
Precautions should be taken to avoid accidental injection/self injection. If accidental self-injection occurs, seek medical advice immediately and show the package leaflet or the label to the physician.
Do not drive.
The effects of butorphanol include sedation, dizziness and confusion. Effects can be reversed with an opioid antagonist such as naloxone.
Wash splashes from skin and eyes immediately.
Adverse Reactions:
Butorphanol may cause the following side effects:
Horse, dog, and cat:
Sedation may be noted in treated animals.
Horse:
- Excitatory locomotor effects (pacing)
- Ataxia
- Reduction in gastrointestinal motility
- Depression of the cardiovascular system.
Dog:
- Depression of the respiratory and cardiovascular system
- Anorexia and diarrhoea
- Reduction in gastrointestinal motility
- Local pain associated with intramuscular injection.
Cat:
- Mydriasis
- Disorientation
- Possible irritation at the injection site in case of repeated administrations
- Mild agitation
- Dysphoria
- Pain on injection
If respiratory depression occurs, naloxone may be used as an antidote.
Use during pregnancy or lactation:
The safety of this veterinary medicinal product has not been established in the target species during pregnancy and lactation. The use of the product during pregnancy and lactation is not recommended.
Interactions:
Butorphanol may be used in combination with other sedatives such as α2-adrenoceptor agonists (e.g. romifidine or detomidine in horses, medetomidine in dogs) where synergistic effects can be expected. Therefore, an appropriate reduction in dose is necessary when used concomitantly with such agent (see section ‘Amounts to be administered’).
Because of its antagonist properties at the opiate mu (µ) receptor butorphanol may remove the analgesic effect in animals, which have already received pure opioid mu (µ) agonists (morphine/oxymorphine).
Amounts to be administered and administration route:
For analgesia:
Horse:
0.05 to 0.1 mg/kg, intravenous route, (i.e. 2.5 to 5 ml for 500 kg bw).
Dog:
0.2 to 0.4 mg/kg, intravenous route, (i.e. 0.2 to 0.4 ml/10 kg bw).
Rapid intravenous injection should be avoided.
Butorphanol is intended for use where short duration analgesia is required. For information on the duration of analgesia that can be expected following treatment see ‘Pharmacological particulars’. However, repeat treatments of butorphanol may be administered. The need for, and timing of repeat treatment will be based on clinical response. For cases where longer duration analgesia is likely to be required, an alternative therapeutic agent should be used.
Cat:
0.4 mg/kg, subcutaneous route, (i.e. 0.2 ml/5 kg bw).
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).
In the cat, butorphanol is intended for use where short to medium duration analgesia is required. For information on the duration of analgesia that can be expected following treatment see section ‘Pharmacological particulars’. Depending on the clinical response, product administration may be repeated within six hours. In the absence of an adequate analgesic response (see section ‘Special warnings for each target species’), use of an alternative analgesic agent, such as another suitable opioid analgesic and/or a non-steroidal anti-inflammatory drug, should be considered. Any alternative analgesia should take account of the action of butorphanol on opioid receptors, as described under section ‘Interactions’.
If repeated administrations are required, use different injection sites.
For sedation:
Butorphanol can be used in combination with an α2-adrenoceptor agonist (e.g. (me)detomidine or romifidine).
Adjustment of the dose will then be necessary according to the following recommendations:
Horse:
Detomidine: 0.01 – 0.02 mg/kg intravenous route.
Butorphanol: 0.01 – 0.02 mg/kg intravenous route.
Detomidine should be administered up to 5 min before butorphanol.
Romifidine: 0.05 mg/kg intravenous route.
Butorphanol: 0.02 mg/kg intravenous route.
Romifidine can be administered concurrently or 4 min before butorphanol.
Dog:
Medetomidine: 0.01 – 0.03 mg/kg intramuscular route.
Butorphanol: 0.1 – 0.2 mg/kg intramuscular route.
Medetomidine and butorphanol can be administered concurrently.
The stopper should not be pierced more than 25 times.
Overdose:
The main sign of overdose is respiratory depression, which, if severe, can be reversed with an opioid antagonist (e.g. naloxone).
Other possible signs of overdose in the horse include restlessness/excitability, muscle tremor, ataxia, hypersalivation, decrease of gastrointestinal motility and seizure. In the cat, the main signs of overdose are incoordination, salivation, and mild convulsions.
Withdrawal periods:
Horse:
Meat and offal: zero days.
Milk: zero hours.
Pharmacological particulars
ATC Vet Code: QN02AF01
Pharmacotherapeutic group: Morphinan derivatives, butorphanol.
Pharmacodynamic properties
Butorphanol tartrate (R(-) enantiomer) is a centrally acting analgesic. Its action is agonist-antagonist at the opiate receptors in the central nervous system, agonist at the kappa (κ) opioid receptor subtype and antagonist at the mu (µ) receptor subtype.
The kappa (κ) receptors control analgesia, sedation without depression of cardiopulmonary system and body temperature, whereas the mu (µ) 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.
Onset and duration of analgesia:
Analgesia generally occurs within 15 minutes following administration in horse, dog and cat. After a single intravenous dose in the horse, analgesia usually lasts for 15 – 60 minutes. In the dog, it lasts for 15-30 minutes after a single intravenous administration. In cats with visceral pain, analgesic effect for 15 minutes up to 6 hours after butorphanol administration has been demonstrated. In cats with somatic pain, the duration of analgesia has been considerably shorter.
Pharmacokinetic properties
In the horse, butorphanol has a high clearance (on average 1.3 L/h/kg) after intravenous administration. It has a short terminal half-life (mean <1 hour), indicating that 97% of a dose will be eliminated after intravenous administration in, on average, less than 5 hours.
In the dog, butorphanol administered by the intramuscular route has a high clearance (around 3.5 L/h/kg). It has a short terminal half-life (mean <2 hours), indicating that 97% of a dose will be eliminated after intramuscular administration in, on average, less than 10 hours. Repeated dose pharmacokinetics and the pharmacokinetics following intravenous administration have not been studied.
In the cat, butorphanol administered by the subcutaneous route has a low clearance (<1320 mL/kg/h). It has a relative long terminal half life (around 6 hours) indicating that 97% of the dose will be eliminated in approximately 30 hours.
Repeated dose pharmacokinetics have not been studied.
Butorphanol is metabolised extensively in the liver and excreted in the urine. The volume of distribution is large, suggesting wide distribution into tissue.
Pharmaceutical particulars
Excipients:
Benzethonium chloride, Sodium citrate, Sodium chloride, Citric acid monohydrate and
Water for injections.
Major incompatibilities:
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.
Shelf-life:
Shelf life of the veterinary medicinal product as packaged for sale: 5 years.
Shelf life after first opening the immediate packaging: 28 days.
Special precautions for storage:
Protect from light. Do not refrigerate or freeze.
Immediate packaging:
Carton with 1 glass vial (type I) of 10 or 50 ml with a halogenated butyl rubber stopper (type I) and an aluminium cap.
Not all pack sizes may be marketed.
Disposal:
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.
Marketing Authorisation Number
Vm 01708/4535
Significant changes
Date of the first authorisation or date of renewal
5 July 2007.
Date of revision of the text
15 August 2017.
Any other information
For animal treatment only. Keep out of sight and reach of children.
Legal category
Legal category: POM-V
GTIN
GTIN description:Dolorex 1x10ml :
GTIN:8713184071156
GTIN description:Dolorex 1x50ml:
GTIN:8713184071163