Dogs, cats and horses.

Dog and cat: post-operative analgesia.

Horse: post‑operative analgesia, in combination with sedation.

Dog and horse: potentiation of the sedative effects of centrally acting agents.

Do not administer by the intrathecal or peridural route.

Do not use pre-operatively for Caesarean section (see Use during pregnancy and lactation).

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

As buprenorphine is metabolised by the liver, its intensity and duration of action may be affected in animals with impaired liver function.

The safety of buprenorphine has not been demonstrated in kittens or puppies less than 7 weeks of age, nor 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 veterinarian.

Safety has not been fully evaluated in clinically compromised cats or horses.

Long-term safety of buprenorphine has not been investigated beyond 5 consecutive days of administration in cats or 4 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. In case of renal, cardiac or hepatic dysfunction, or shock, there may be greater risk associated with the use of the product. In all of these cases the product should be used in accordance with the benefit risk assessment of the attending veterinarian.

Buprenorphine may occasionally 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.

Repeat administration earlier than the recommended repeat interval suggested in Amounts to be administered and administration route is not recommended.

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.

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.

As 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.

The product may cause skin or eye irritation or hypersensitivity reactions if contact occurs. Following eye, skin or mouth contact, wash the affected area thoroughly with water. Seek medical advice in case of hypersensitivity reactions or if irritation persists. Wash hands after use.

To the physician: Naloxone should be available in case of accidental self-injection.

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.

In horses, use of buprenorphine without the prior use of a sedative agent can cause excitement and spontaneous locomotor activity.

Buprenorphine may occasionally cause respiratory depression; refer to Special precautions for use in animals.

In horses, when used as directed in conjunction with sedatives or tranquillisers, excitation is minimal but ataxia may occasionally be marked. Buprenorphine may reduce gastrointestinal motility in horses but 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 effects. However, these studies have shown post-implantation losses and early foetal deaths. 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 accordingly to 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, alphaxalone/alphadalone, 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.

When used in horses, an intravenous sedative must be administered within five minutes prior to injection of buprenorphine.

In dogs, sedative effects are present by 15 minutes after administration.

Analgesic activity may not develop fully until 30 minutes. To ensure that analgesia is present during surgery and immediately on recovery, the product should be administered preoperatively as part of premedication. When administered for potentiation of sedation or as part of premedication, the dose of other centrally-acting agents, such as acepromazine or medetomidine, should be reduced. The reduction will depend on the degree of sedation required, the individual animal, the type of other agents included in premedication and how anaesthesia is to be induced and maintained. It may also be possible to reduce the amount of inhalational anaesthetic used.

Animals administered opioids possessing sedative and analgesic properties may show variable responses. Therefore, the response of individual animals should be monitored and subsequent doses should be adjusted accordingly. In some cases, repeat doses may fail to provide additional analgesia. In these cases, consideration should be given to using a suitable injectable NSAID.

An appropriately graduated syringe must be used to allow accurate dosing.

The closure must not be punctured more than 100 times (with a 21G or 23G needle).

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 can cause excitement.

When used to provide analgesia in horses, sedation is rarely seen, but may occur at dose levels higher than those recommended.

Naloxone may be of benefit in reversing reduced respiratory rate.

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.

Please also refer to Special precautions for use and Adverse reactions in this datasheet.

The product is not authorised for use in horses intended for human consumption.