4.1 Target species
Dogs, cats and pet rabbits
4.2 Indications for use, specifying the target species
As an induction agent prior to inhalation anaesthesia in dogs, cats and pet rabbits.
As a sole anaesthetic agent for the induction and maintenance of anaesthesia for the performance of examination or surgical procedures in dogs and cats.
4.3 Contraindications
Do not use in combination with other intravenous anaesthetic agents.
Do not use on animals with hypersensitivity to the active substance or any other excipients.
4.4 Special warnings for each target species
The analgesic properties of alfaxalone are limited, therefore appropriate peri-operative analgesia should be provided in cases where procedures are anticipated to be painful.
4.5 Special precautions for use
(i) Special precautions for use in animals
The safety of the veterinary medicinal product in animals less than 12 weeks of age (dogs and cats) and 16 weeks of age (rabbits) has not been demonstrated.
Transient post induction apnoea frequently occurs, particularly in dogs – see section 4.6 for details. In such cases, endotracheal intubation and oxygen supplementation should be employed. Facilities for intermittent positive pressure ventilation should be available. In order to minimise the possibility of apnoea, administer the veterinary medicinal product by slow intravenous injection and not as a rapid dose.
In rabbits, oxygenation prior to administration of the product for induction of anaesthesia is essential in order to reduce the risk of life threatening hypoxaemia post induction, which can occur secondary to respiratory depression or apnoea.
In rabbits, an intravenous catheter should be used to administer the product due to the possibility of reactions (e.g. head shaking and scratching at ear) during administration (please refer to section 4.6). The use of a preplaced catheter in dogs and cats is also recommended as best practice for anaesthetic procedures.
Especially when using higher doses of the veterinary medicinal product, a dose-dependent respiratory depression may occur. Oxygen and/or intermittent positive pressure ventilation should be administered to counteract the threatening hypoxaemia/hypercapnea. This should be particularly important in risky anaesthetic cases and whenever the anaesthesia is to be carried out for a longer period of time. In rabbits, oxygenation is essential before induction of anaesthesia and throughout the entire anaesthetic procedure.
In dogs and cats, the dose interval for maintenance of anaesthesia by intermittent bolus administration may require lengthening by more than 20%, or the maintenance dose by intravenous infusion may require reduction by more than 20%, when hepatic blood flow is severely diminished or hepatocellular injury is severe. In cats or dogs with renal insufficiency, doses for induction and maintenance may require reduction.
As with all general anaesthetic agents:
• It is advisable to ensure that dogs and cats have been fasted before receiving the anaesthetic. Rabbits should not be fasted, but food should be removed one hour before anaesthesia.
• As with other intravenous anaesthetic agents, caution should be exercised in animals with cardiac or respiratory impairment, or in hypovolaemic or debilitated animals.
• Additional monitoring is advised and particular attention should be paid to respiratory parameters in aged animals, or in cases where there may be additional physiological stress imposed by pre-existing pathology, shock or caesarean section.
• Following induction of anaesthesia, the use of an endotracheal tube is recommended to maintain airway patency.
• It is advisable to administer supplemental oxygen during maintenance of anaesthesia.
• Respiratory embarrassment may occur – ventilation of the lungs with oxygen should be considered if haemoglobin saturation with oxygen (SpO2%) falls below 90% or if apnoea persists for longer than 60 seconds.
• If cardiac arrhythmias are detected, attention to respiratory ventilation with oxygen is the first priority followed by appropriate cardiac therapy or intervention.
During recovery, it is preferable that animals are not handled or disturbed. In dogs and cats, this may lead to paddling, minor muscle twitching or movements that are more violent. While better avoided, such reactions are clinically insignificant. Post-anaesthetic recovery should thus take place in appropriate facilities and under sufficient supervision. Use of a benzodiazepine as the sole premedicant in dogs and cats may increase the probability of psychomotor excitement.
Muscle twitching/tremors may be observed in a small proportion of rabbits anaesthetised with the veterinary medicinal product. However, such reactions are not considered to be clinically significant.
(ii) Special precautions to be taken by the person administering the veterinary medicinal product to animals
This product is a sedative, exercise caution to avoid accidental self-injection.
Preferably use a guarded needle until the moment of injection.
In case of accidental self-injection seek immediate medical attention and show the product literature.
The product may cause irritation if it comes into contact with the skin or eyes.
Rinse any splashes from skin or eyes immediately with water.
4.6 Adverse reactions (frequency and seriousness)
In clinical studies using the veterinary medicinal product, post induction apnoea, which was defined as the cessation of breathing for 30 seconds or more, was very common in dogs and cats, and common in rabbits.
Based on post marketing safety experience, neurological signs (convulsions, myoclonus, tremor, prolonged anaesthesia), cardio respiratory signs (cardiac arrests, bradycardia, bradypnea) and behavioural signs (hyperactivity, vocalisation) have been reported very rarely (.
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).
The mean duration of apnoea in these animals was 100 seconds in dogs, 60 seconds in cats and 53 seconds in rabbits. Endotracheal intubation and oxygen supplementation should therefore be employed.
In rabbits, defensive reactions (such as head-shaking, ear flicking and backing away) are commonly observed during intravenous (marginal ear vein) administration and, therefore, administration of the product via a pre-placed catheter in the marginal ear vein is recommended. Premedication may also prevent these reactions. In a field study, these reactions were not observed when rabbits had been premedicated with medetomidine in combination with either butorphanol or buprenorphine.
4.7 Use during pregnancy, lactation or lay
The safety of the veterinary medicinal product has not been established in cases where pregnancy is to be continued or during lactation. Its effects upon fertility have not been evaluated. However, studies using alfaxalone in pregnant mice, rats and rabbits have demonstrated no deleterious effects on gestation of the treated animals, or on the reproductive performance of their offspring. The product should be used in pregnant animals according to the risk-benefit assessment performed by the veterinarian. The product has been safely used in dogs for the induction of anaesthesia prior to delivery of puppies by caesarean section. In these studies, dogs were not premedicated, a dose of 1-2 mg/kg was drawn up (i.e. slightly lower than the usual 3 mg/kg dose, see section 4.9) and the product was administered as recommended, to effect.
