Do not administer by the intrathecal or peridural route.
Do not use pre-operatively for Caesarean section.
Do not use in cases of hypersensitivity to the active substance or to any of the excipients.
Buprenorphine may cause respiratory depression and as with other opioid drugs, care should be taken when treating animals with impaired respiratory function or animals that are receiving drugs that can cause respiratory depression.
In case of renal, cardiac or hepatic dysfunction or shock, there may be greater risk associated with the use of the product. The benefit-risk assessment for using the product should be made by the attending vet. Safety has not been fully evaluated in clinically compromised cats.
Buprenorphine should be used with caution in animals with impaired liver function, especially biliary tract disease, as the substance is metabolised by the liver and its intensity and duration of action may be affected in such animals.
The safety of buprenorphine has not been demonstrated in animals less than seven-weeks of age, therefore, use in such animals should be based on the benefit-risk assessment of the responsible veterinarian.
Repeat administration earlier than the recommended repeat interval suggested in Dosage and Administration is not recommended.
Long-term safety of buprenorphine has not been investigated beyond five consecutive days of administration in cats or four separate administrations on three consecutive days in horses.
The effect of an opioid on head injury is dependent on the type and severity of the injury and the respiratory support supplied. The product should be used in accordance with the benefit-risk assessment of the responsible veterinarian.
Safety has not been evaluated in clinically-compromised horses. In horses, use of opioids has been associated with excitation, but effects with buprenorphine are minimal when administered in conjunction with sedatives and tranquilisers such as detomidine, romifidine, xylazine and acepromazine. The safety of buprenorphine has not been demonstrated in horses younger than 10 months old and weighing less than 150 kg; therefore, use in such animals should be based on the benefit: risk assessment of the responsible veterinarian.
Ataxia is a known effect of detomidine and similar agents; consequently it may be seen after administration of buprenorphine with such substances. Occasionally, ataxia may be marked. To ensure ataxic horses sedated with detomidine/buprenorphine do not lose their balance, they should not be moved or otherwise handled in any way that would compromise their stability.
Salivation, bradycardia, hypothermia, agitation, dehydration and miosis can occur in the dog, and rarely hypertension and tachycardia.
Mydriasis and signs of euphoria (excessive purring, pacing, rubbing) commonly occur in cats and will usually resolve within 24 hours.
Buprenorphine may cause respiratory depression. When used to provide analgesia in horses, sedation is rarely seen, but may occur at dose levels higher than those recommended.
When used in conjunction with sedatives or tranquillisers, excitation is normally minimal, but ataxia may occasionally be marked. Colic is rarely reported.
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).
Pregnancy:
Laboratory studies in rats have not produced any evidence of a teratogenic effect. However, these studies have shown post-implantation losses and early foetal deaths. These may have resulted from a reduction in parental body condition during gestation and in post-natal care owing to sedation of the mothers.
As reproductive toxicity studies have not been conducted in the target species, use only according to the benefit-risk assessment by the responsible veterinarian.
The product should not be used pre-operatively in cases of Caesarean section, due to the risk of respiratory depression in the offspring periparturiently and should only be used post-operatively with special care (see below).
Lactation:
Studies in lactating rats have shown that, after intramuscular administration of buprenorphine, concentrations of unchanged buprenorphine in the milk equalled or exceeded that in the plasma. As it is likely that buprenorphine will be excreted in the milk of other species, use is not recommended during lactation. Use only according to the benefit-risk assessment by the responsible veterinarian.
Buprenorphine may cause some drowsiness, which may be potentiated by other centrally acting agents, including tranquillisers, sedatives and hypnotics.
There is evidence in humans to indicate that therapeutic doses of buprenorphine do not reduce the analgesic efficacy of standard doses of an opioid agonist and that when buprenorphine is employed within the normal therapeutic range, standard doses of opioid agonist may be administered before the effects of the former have ended without compromising analgesia. However, it is recommended that buprenorphine is not used in conjunction with morphine or other opioid-type analgesics, e.g. etorphine, fentanyl, pethidine, methadone, papaveretum or butorphanol.
Buprenorphine has been used with acepromazine, alfaxalone/alfadolone, atropine, detomidine, dexmedetomidine, halothane, isoflurane, ketamine, medetomidine, propofol, romifidine, sevoflurane, thiopentone and xylazine. When used in combination with sedatives, depressive effects on heart rate and respiration may be augmented.
In cases of overdosage, supportive measures should be instituted, and, if appropriate, naloxone or respiratory stimulants may be used.
When administered at overdose to dogs, buprenorphine may cause lethargy. At very high doses, bradycardia and miosis may be observed.
Studies in horses where buprenorphine has been administered with sedatives have shown very few effects at up to five times the recommended dosage, but when administered on its own it may cause excitement in pain-free-animals.
Naloxone may be of benefit in reversing reduced respiratory rate and respiratory stimulants such as Doxapram are also effective in man. Because of the prolonged duration of effect of buprenorphine in comparison to such drugs, they may need to be administered repeatedly or by continuous infusion. Volunteer studies in man have indicated that opiate antagonists may not fully reverse the effects of buprenorphine.
In toxicological studies of buprenorphine hydrochloride in dogs, biliary hyperplasia was observed after oral administration for one year at dose levels of 3.5 mg/kg/day and above. Biliary hyperplasia was not observed following daily intramuscular injection of dose levels up to 2.5 mg/kg/day for 3 months. This is well in excess of any clinical dose regimen in the dog.
Withdrawal period:
Not authorised for use in horses intended for human consumption.
User warnings:
Buprenorphine has opioid-like activity. Care should be taken to avoid self-injection. In case of accidental self-injection or ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. Naloxone should be available in case of accidental self-injection.
Buprenorphine may be absorbed systemically on exposure to mucous membranes. The product may cause skin or eye irritation if contact occurs. Avoid contact with skin and eyes. In case of accidental spillage onto the skin or eyes, wash the affected area thoroughly with running water. Seek medical advice if irritation persists.