ANNEX III
LABELLING AND PACKAGE LEAFLET
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A. LABELLING
version 2020/11 page 2 of 12 PARTICULARS TO APPEAR ON THE OUTER PACKAGE
Outer carton
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
Butorgesic 10 mg/ml solution for injection butorphanol
2. STATEMENT OF ACTIVE SUBSTANCES
Active substance: butorphanol 10.00 mg/ml (as butorphanol tartrate 14.58 mg/ml)
Excipients: benzethonium chloride 0.10 mg/ml
3. PHARMACEUTICAL FORM
Solution for injection
4. PACKAGE SIZE
10 ml 20 ml
5. TARGET SPECIES
Horse, dog and cat
6. INDICATION(S)
7. METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use. Horse: IV Dog, Cat: IV, SC, IM
8. WITHDRAWAL PERIOD(S)
Withdrawal period(s): Horse (meat, offal, milk): zero days
9. SPECIAL WARNING(S), IF NECESSARY
Read the package leaflet before use.
10. EXPIRY DATE
EXP {month/year} version 2020/11 page 3 of 12 Once opened use within 28 days.
11. SPECIAL STORAGE CONDITIONS
Keep the vial in the outer carton in order to protect from light.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR WASTE MATERIALS, IF ANY
Disposal: read package leaflet.
13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE, IF APPLICABLE
For animal treatment only. To be supplied only on veterinary prescription.
14. THE WORDS “KEEP OUT OF THE SIGHT AND REACH OF CHILDREN”
Keep out of the sight and reach of children.
15. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
ADOH B.V. Godfried Bomansstraat 31 6543 JA Nijmegen The Netherlands
16. MARKETING AUTHORISATION NUMBER(S)
17. MANUFACTURER’S BATCH NUMBER
Lot {number}
version 2020/11 page 4 of 12 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
10 ml, 20 ml vials
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
Butorgesic 10 mg/ml solution for injection butorphanol
2. QUANTITY OF THE ACTIVE SUBSTANCE(S) butorphanol 10.00 mg/ml (as butorphanol tartrate 14.58 mg/ml)
Excipients: benzethonium chloride 0.10 mg/ml
3. CONTENTS BY WEIGHT, BY VOLUME OR BY NUMBER OF DOSES
10 ml 20 ml
4. ROUTE(S) OF ADMINISTRATION
Horse: IV Dog, Cat: IV, SC, IM
5. WITHDRAWAL PERIOD
Withdrawal period(s): Horse (meat, offal, milk): zero days
6. BATCH NUMBER
Lot {number}
7. EXPIRY DATE
EXP {month/year} Once opened use within 28 days.
8. THE WORDS “FOR ANIMAL TREATMENT ONLY”
For animal treatment only
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B. PACKAGE LEAFLET
version 2020/11 page 6 of 12 PACKAGE LEAFLET FOR:
Butorgesic 10 mg/ml solution for injection
I1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE, IF DIFFERENT
Marketing authorisation holder: ADOH B.V. Godfried Bomansstraat 31 6543 JA Nijmegen The Netherlands
Manufacturer responsible for batch release: CP-Pharma Handelsgesellschaft mbH Ostlandring 13 31303 Burgdorf Germany
I2. NAME OF THE VETERINARY MEDICINAL PRODUCT
Butorgesic 10 mg/ml solution for injection butorphanol
I3. STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENTS
1 ml of solution for injection contains:
Active substance: butorphanol 10.00 mg (as butorphanol tartrate 14.58 mg)
Excipients: benzethonium chloride 0.10 mg
Clear, colourless solution.
I4. INDICATION(S)
Horse: As an analgesic Relief of abdominal pain caused by colic of gastrointestinal origin.
As a sedative (in combination) For therapeutic and diagnostic measures such as minor surgical procedures on the standing horse. For sedation in combination with certain α2-adrenoceptor-agonists (detomidine, romifidine).
Dog: As an analgesic Relief of mild to moderate visceral pain and mild to moderate pain after soft tissue surgery.
As a sedative (in combination) For deep sedation in combination with medetomidine.
version 2020/11 page 7 of 12 As a pre-anaesthetic Pre-anaesthetic use of the product has resulted in a dose related reduction in the dose of induction anaesthetic agents.
As an anaesthetic (in combination) As part of anaesthesia in combination with medetomidine and ketamine.
Cat: As an analgesic To alleviate moderate postoperative pain after soft tissue surgery and minor surgical procedures.
As a sedative (in combination) For deep sedation in combination with medetomidine.
As an anaesthetic (in combination) As part of anaesthesia in combination with medetomidine and ketamine.
I5. CONTRAINDICATIONS
All target species Do not use in cases of hypersensitivity to the active substance or to any of the excipients. Do not use in cases of severe dysfunctions of liver or/and kidney. Do not use in cases of head trauma or organic brain lesions as well in animals with obstructive respiratory disease, heart failure or spastic conditions.
Horse: Butorphanol/detomidine hydrochloride combination: Do not use in horses with a pre-existing cardiac arrhythmia or bradycardia. The combination causes impaired movement of the gastrointestinal system and should therefore not be used in the case of colic associated with constipation. Do not use in horses with lung emphysema due to a possible breathing depressive effect.
See also section 12.
I6. ADVERSE REACTIONS
There may be some pain on intramuscular injection.
Horse: The most commonly observed side effect is slight ataxia (lack of voluntary coordination of muscle movements) which may persist for 3-10 minutes. Mild to severe ataxia may be encountered in combination with detomidine, but clinical studies have shown that horses are unlikely to collapse. Normal precautions should be observed to prevent patient self-injury. Mild sedation may occur in approximately 15% of horses following the administration of butorphanol as a sole agent.
Intravenous bolus injection with the highest permissible dose may cause excitatory locomotor effects (e.g. walking around). Restlessness, tremors and sedation with subsequent restlessness has been observed in some horses. Butorphanol can lower the intestinal motility in horses (impaired movement of the gastrointestinal system), although the gastrointestinal passage time does not decrease. This effect is dose-dependent and usually minor and temporary. Butorphanol can stimulate motor activity (walking movements). When used in combination with α2-adrenoceptor-agonists (e.g. detomidine, romifidine), cardiopulmonary depression may occur, which in rare cases can be fatal.
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Dog: Respiratory and cardiac depression (evidenced by the decrease in respiratory rate, the development of bradycardia and the decrease of the diastolic blood pressure) may occur, with the degree of depression being dose-dependent. A slight sedation can also occur. Transient ataxia, anorexia, and diarrhoea have been reported as occurring rarely. Gastrointestinal motility may be reduced.
Cat: Respiratory depression may occur. Butorphanol can cause arousal, anxiety, confusion, dysphoria and mydriasis.
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)
If you notice any side effects, even those not already listed in this package leaflet or you think that the medicine has not worked, please inform your veterinary surgeon.
Alternatively, you can report via your national reporting system {national system details}.
I7. TARGET SPECIES
Horse, dog and cat.
I8. DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION
Horse: intravenously (IV). Dog and Cat: intravenous (IV), subcutaneous (SC) and intramuscular (IM). When administering as an intravenous injection, do no inject as a bolus. If repeat SC or IM administrations are required, use different injection sites. The rubber stopper should not be pierced more than 20 times.
HORSE
As an analgesic Monotherapy: 0.1 mg of butorphanol /kg (1 ml of product /100 kg) IV. The dose may be repeated as required. Analgesic effects are seen within 15 minutes of injection.
As a sedative With detomidine: Detomidine hydrochloride: 0.012 mg/kg IV, followed within 5 minutes by Butorphanol: 0.25 ml/100 kg IV.
With romifidine: Romifidine: 0.04 - 0.12 mg/kg IV, followed within 5 minutes by Butorphanol: 0.2 ml/100 kg IV.
DOG
version 2020/11 page 9 of 12 As an analgesic Monotherapy: 0.2-0.3 mg butorphanol /kg (0.02-0.03 ml of product /kg) IV, IM or SC injection. Administer 15 minutes before terminating anaesthesia to provide analgesia in the recovery phase. Repeat dose as required.
As a sedative With medetomidine: Butorphanol: 0.01 ml/kg IV or IM Medetomidine: 0.01-0.025 mg/kg IV or IM. Allow 20 minutes for sedation to develop before commencing the procedure.
As a pre-anaesthetic Monotherapy for canine analgesia: 0.1-0.2 mg butorphanol /kg (0.01-0.02 ml of product /kg) IV, IM or SC given 15 minutes prior to induction.
As an anaesthetic In combination with medetomidine and ketamine: Butorphanol: 0.01 ml/kg IM Medetomidine: 0.025 mg/kg IM, followed after 15 minutes by Ketamine: 5 mg/kg IM. It is not advisable to reverse this combination in the dog with atipamezole.
CAT
As an analgesic Pre-operative: 0.4 mg butorphanol /kg (0.04 ml of product/ kg) IM or SC Administer 15-30 minutes prior to the administration of IV induction anaesthetic agents. Administer 5 minutes before induction with IM induction anaesthetic agents such as combinations of IM acepromazine/ketamine or xylazine/ketamine. See also section 5.1. for duration of analgesia.
Post-operative: Administer 15 minutes before terminating anaesthesia to provide analgesia in the recovery phase: either 0.4 mg butorphanol /kg (0.04 ml of product /kg) SC or IM or: 0.1 mg butorphanol /kg (0.01 ml of product /kg) IV.
As a sedative With medetomidine: Butorphanol: 0.04 ml/kg IM or SC. Medetomidine: 0.05 mg/kg SC. Additional local anaesthesia should be used for wound suturing.
As an anaesthetic In combination with medetomidine and ketamine:
IM administration: Butorphanol: 0.04 ml/kg IM Medetomidine: 0.08 mg/kg IM Ketamine: 5 mg/kg IM.
IV administration: Butorphanol: 0.01 ml/kg IV Medetomidine: 0.04 mg/kg IV Ketamine: 1.25-2.50 mg/kg IV (depending on depth of anaesthesia required). version 2020/11 page 10 of 12
I9. ADVICE ON CORRECT ADMINISTRATION
See section 8. The rubber stopper should not be pierced more than 20 times.
10. WITHDRAWAL PERIOD(S)
Horse Meat and offal: zero days. Milk: zero days.
11. SPECIAL STORAGE PRECAUTIONS
Keep out of the sight and reach of children. Keep the vial in the outer carton in order to protect from light. Do not use this veterinary medicinal product after the expiry date which is stated on the label. The expiry date refers to the last day of that month.
Shelf life of the veterinary medicinal product as packaged for sale: 3 years. Shelf life after first opening the immediate packaging: 28 days.
12. SPECIAL WARNING(S)
Before using any combinations consult the contraindications, withdrawal periods and warnings that appear on the other products’ SPCs.
Special precautions for use in animals: In treated animals, a noticeable sedation may occur.
Horse: The use of the product at the recommended dose can cause temporary ataxia (lack of voluntary coordination of muscle movements) and / or overexcitation. The location and of treatment should be carefully chosen to prevent injury to the animal or the person administering the product.
Butorphanol/detomidine hydrochloride combination: Routine cardiac auscultation should be performed prior to use in combination with detomidine.
Dog: If respiratory depression occurs, naloxone may be used as an antidote. When using Butorphanol as a pre-anaesthetic, the use of an anticholinergic such as atropine, will protect the heart against possible narcotic-induced bradycardia. When administering as an intravenous injection, do not inject rapidly as a bolus.
Cat: If respiratory depression occurs, naloxone may be used as an antidote. Cats should be weighed to ensure that the correct dose is calculated. Use of either insulin syringes or 1 ml graduated syringes is recommended.
Special precautions to be taken by the person administering the veterinary medicinal product to animals: Butorphanol has opioid-like activity. In case of accidental self-injection, seek medical advice immediately and show the package insert or the label to the physician. Do not drive, since drowsiness, sweating, nausea, dizziness and vertigo may occur. Effects can be reversed by the administration of an opioid antagonist (e.g. naloxone). Accidental spillage on the skin and eyes should be washed immediately with water.
Pregnancy: version 2020/11 page 11 of 12 The use of butorphanol is not recommended during pregnancy.
Lactation: The use of butorphanol is not recommended during lactation.
Interaction with other medicinal products and other forms of interaction When butorphanol is used in combination with particular sedatives such as adrenergic α2-agonists (romifidine or detomidine in horses, medetomidine in dogs and cats) synergistic effects occur which require a reduction in butorphanol dose. See section 8.
Butorphanol has antitussive properties and should not be used in combination with an expectorant (mucoactive agent), as this can lead to accumulation of mucus in the respiratory tract.
Butorphanol can reverse the analgesic effect of pure μ-opioid analgesics (e.g. morphine / oxymorphine) in animals that have already received these agents.
The simultaneous use of other central nervous system sedatives is expected to increase the effects of butorphanol, so these drugs should be used with caution. A reduced dose of butorphanol should be given when these agents are administered simultaneously.
Overdose (symptoms, emergency procedures, antidotes): The main sign of overdose is respiratory depression, which can be reversed with naloxone. To reverse the effect of combinations with detomidine/medetomidine, atipamezole may be used, except when a combination of butorphanol, medetomidine, and ketamine has been used intramuscularly to produce anaesthesia in the dog. In this case, atipamezole should not be used.
Incompatibilities: In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products in the same syringe.
13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY
Medicines should not be disposed of via wastewater or household waste. Ask your veterinary surgeon how to dispose of medicines no longer required. These measures should help to protect the environment.
14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED
15. OTHER INFORMATION
Pack sizes: Cardboard box containing 1 bottle of 10 or 20 ml.
Not all pack sizes may be marketed.
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