Alfaxan Multidose contains 10 mg/ml alfaxalone and the excipients ethanol (150 mg/ml), chlorocresol (1 mg/ml) and benzethonium chloride (0.2 mg/ml).

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.

For intravenous use

The induction dose of the veterinary medicinal product is based on data taken from controlled laboratory and field studies and is the amount of drug required for 9 of 10 patients (i.e. 90th percentile) to be successfully induced for anaesthesia.

Dosing recommendations for induction of anaesthesia are as follows:

In dogs, cats and rabbits, an intravenous catheter should be used to administer the product (please refer to contra-indications, warnings etc).

The dosing syringe should be prepared to contain the above dose. Administration should continue until the clinician is satisfied that the depth of anaesthesia is sufficient for endotracheal intubation, or until the entire dose has been administered. The necessary injection rate can be achieved by administration of one quarter (¼) of the calculated dose every 15 seconds, so that the total dose, if required, would be administered over the first 60 seconds. If, 60 seconds after complete delivery of this first induction dose, intubation is still not possible, one further similar dose may be administered to effect.

Following induction of anaesthesia with the veterinary medicinal product, the animal may be intubated and maintained on the veterinary medicinal product or an inhalation anaesthetic agent. Maintenance doses of the veterinary medicinal product may be given as supplemental boluses or as constant rate infusion. The veterinary medicinal product has been used safely and effectively in dogs and cats for procedures lasting for up to one hour. The following doses suggested for maintenance of anaesthesia are based on data taken from controlled laboratory and field studies and represent the average amount of drug required to provide maintenance anaesthesia for a dog or cat. However, the actual dose will be based on the response of the individual patient.

Dosing recommendations for maintenance of anaesthesia are as follows:

Where maintenance of anaesthesia is with the veterinary medicinal product for procedures lasting more than 5 to 10 minutes, a butterfly needle or catheter can be left in the vein, and small amounts of the veterinary medicinal product injected subsequently to maintain the required level and duration of anaesthesia. In most cases the average duration of recovery when using the veterinary medicinal product for maintenance will be longer than if using an inhalant gas as a maintenance agent.

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.

The analgesic properties of alfaxalone are limited, therefore appropriate peri-operative analgesia should be provided in cases where procedures are anticipated to be painful.

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 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. 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:

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.

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:

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.

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) and the product was administered as recommended to effect.

In dogs and cats, the veterinary medicinal product has been demonstrated to be safe when used in combination with the following premedicant classes:

During clinical studies in rabbits, the veterinary medicinal product was used safely with the following premedicant combinations: (i) medetomidine hydrochloride in combination with buprenorphine hydrochloride or butorphanol tartrate, and (ii) midazolam hydrochloride in combination with buprenorphine hydrochloride or butorphanol tartrate.

The concomitant use of other CNS depressants should be expected to potentiate the depressant effects of the veterinary medicinal product, necessitating cessation of further administration of the veterinary medicinal product when the required depth of anaesthesia has been reached.

The use of one premedicant or a combination of premedicants often reduces the dose of the veterinary medicinal product required.

Premedication with alpha-2-adrenoceptor agonists such as xylazine and medetomidine can markedly increase the duration of anaesthesia in a dose dependent fashion. In order to shorten recovery periods it may be desirable to reverse the actions of these premedicants.

Benzodiazepines should not be used as sole premedicants in dogs and cats as the quality of anaesthesia in some patients may be sub-optimal. Benzodiazepines may be used safely and effectively in combination with other premedicants and the veterinary medicinal product.

Acute tolerance to overdose has been demonstrated up to 10 times the recommended dose of 2 mg/kg in the dog (i.e. up to 20 mg/kg), up to 5 times the recommended dose of 5 mg/kg in the cat (i.e. up to 25 mg/kg) and up to 3 times the recommended dose in the rabbit (i.e. up to 15 mg/kg). These excessive doses delivered over 60 seconds caused apnoea and a temporary decrease in mean arterial blood pressure. The decrease in blood pressure is not life threatening and is compensated for by changes in heart rate. These animals can be treated solely by intermittent positive pressure ventilation (if required) with either room air or, preferably, oxygen. Recovery is rapid with no residual effects.

Do not use in rabbits intended for human consumption.

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.

Store below 25°C. Keep the container in the outer carton in order to protect from light.

Shelf life after first opening the immediate packaging: 28 days.

Any unused veterinary medicinal product or waste material derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

Keep out of the sight and reach of children.

For animal treatment only.

Cardboard box with one glass vial of 10 ml or 20 ml with a bromobutyl rubber stopper and aluminium cap. Not all pack sizes may be marketed.

Jurox (UK) Limited

In cats following a single intravenous dose of alfaxalone at 5 mg/kg bw, the mean plasma elimination half-life (t1/2) is approximately 45 minutes. Plasma clearance is 25 ml/kg/min. Volume of distribution is 1.8 L/kg.

In dogs following a single intravenous dose of alfaxalone at 2 mg/kg bw, the mean plasma elimination half-life (t1/2) is approximately 25 minutes. Plasma clearance is 59 ml/kg/min. Volume of distribution is 2.4 L/kg.

In rabbits following a single intravenous dose of alfaxalone at 5 mg/kg bw, the mean plasma elimination half-life (t1/2) is approximately 46 minutes. Plasma clearance is 56 ml/kg/min. Volume of distribution is 3.6 L/kg.

In dogs, cats and rabbits the elimination of alfaxalone demonstrates non-linear (dose-dependent) pharmacokinetics.

Vm 42058/4218