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References:
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| 1 Jurox Pharmacovigilance report JX9604-SR004.2005 |
| 2 Muir, W., et al., Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs. Veterinary Anaesthesia and Analgesia, 2008 |
| 3 Muir, W., et al., The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats. Veterinary Anaesthesia and Analgesia, 2009. 36(1): p. 42-54 |
| 4 Ferre, P.J., et al., Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan –CD RTU. Vet Anaesth Analg, 2006. 33(4); P. 229-36 |
| 5 Whittem, T., et al., The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan at clinical and supraclinical doses. J Vet Pharmacol Ther, 2008. 31(6): p 571-9. |
| 6 Jurox studies: RD9604.03-H002 and JX9604.07-H001 |
| 7 Jurox studies: JX9604.03-E017, JX9604.03-CO16, JX9604.07-H009 and JX9604.07-C006 |
8 Jurox study number JX9604.03/06 (dog), RD9604.03/01 (cat) |
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| Alfaxan® FAQ's |
| Here is the list of the most frequently asked questions about Alfaxan®. We hope that you will find this information useful in your every-day anaesthetic practice. |
What is Alfaxan®?
Alfaxan® is an injectable anaesthetic agent for induction and maintenance of general anaesthesia in dogs and cats. Alfaxan® is a clear, colourless, aqueous solution of alfaxalone (3-alpha-hydroxy-5-alpha-pregnane-11,20-dione), a neuroactive steroid molecule with properties of a general anaesthetic. |
The alfaxalone molecule is solubilised in the Alfaxan® formulation using 2 alpha- hydroxypropyl ß cyclodextrin. Cyclodextrins are complex polysaccharides derived from starch that supply a hydrophobic centre for lipophilic drugs like alfaxalone.
Unlike Cremaphor® EL,
HPCD (2 alpha-hydroxypropyl ß cyclodextrin) does not cause histamine release in dogs and cats.
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How does Alfaxan® work?
The primary mechanism for the anaesthetic action of alfaxalone is modulation of neuronal cell membrane chloride ion transport, induced by binding of alfaxalone to GABAA cell surface receptors. |
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Which pre-meds can be used with Alfaxan®?
Table below contains pre-meds that are most commonly used with Alfaxan®.
| Drug Class |
Examples |
| Phenothiazines |
acepromazine maleate |
| Benzodiazepines |
diazepam, midazolam hydrochloride, |
| Alpha-2-adrenoceptor agonists |
xylazine hydrochloride, medetomidine hydrochloride |
| Opiates |
buprenorphine hydrochloride, butorphanol tartrate,
morphine sulfate, methadone |
| NSAIDs |
carprofen, meloxicam |
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, however, may be used safety and effectively in combination with other premedicants and Alfaxan®.
As with all pre-medication regimes, it is important to allow enough time for the pre-medication to be effective before starting induction. The duration of action in relation to the time and length of the procedure should also be taken into account. For the latest information about the times to peak sedation and duration of action of premedicant and sedative drugs please click here (Reproduced with permission from the BSAVA Manual of Canine and Feline Anaesthesia and Analgesia, 2nd edition. Copyright BSAVA.). |
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| Why should Alfaxan® be injected slowly, over 60 seconds? |
It takes about 20-30 seconds for Alfaxan® injected into the cephalic vein to reach the brain. If Alfaxan® is injected as a bolus, then less time is available for brain absorption of the alfaxalone needed to induce anaesthesia. A lower total amount of alfaxalone crosses the blood-brain barrier, but higher initial concentrations might be reached in the brain.
This has two consequences: |
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the higher initial concentration in the brain is more likely
to cause unwanted side-effects such as apnoea |
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not all the drug will cross into the brain and the rest will
re-distribute into the other tissues and will be wasted, resulting in shorter, less satisfactory anaesthesia
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By giving Alfaxan® slowly, over 60 seconds, one ensures that there is a steady increase in blood concentration
(and therefore brain concentration), which leads to smoother induction into anaesthesia. The injection can be stopped when the brain concentration is just at the required level. |
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Can I inject other drugs
in the same syringe?
We do not recommend the concurrent injection of any drug in the same syringe. |
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What happens if I inject
the drug extra-vascularly?
Alfaxan® does not cause irritation if injected extra-vascularly1 |
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| Can Alfaxan® be used
to maintain anaesthesia? |
Yes. Alfaxan® can be used to maintain anaesthesia either
by ‘topping up’ as required or by constant rate infusion. Recommended dosages are listed in the table below.
DOG Maintenance |
Cat Maintenance |
Constant
rate
infusion
(6-7mg/kg/hour
of alfaxalone)
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Bonus dose
each 10min
maintenance
(1.0-1.2mg/kg
of alfaxalone)
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Constant
rate
infusion
(7-8mg/kg/hour
of alfaxalone)
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Bonus dose
each 10min
maintenance
(1.1-1.3mg/kg
of alfaxalone)
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Alfaxan® dose (kg/ml/hour) |
Alfaxan® dose (kg/ml/every 10min) |
Alfaxan® dose (kg/ml/hour) |
Alfaxan® dose (kg/ml/every 10min) |
0.6 - 0.7 |
0.1 - 0.12 |
0.7 - 0.8 |
0.11 - 0.13 |
Please refer to the Alfaxan® dosage chart for more information about “topping up” dosage rates. For further information about constant rate infusion dosages please click here. |
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Alfaxan® safety margin:
Alfaxan® has a very wide safety margin:
In an acute tolerance study all dogs survived IV injection of Alfaxan® at 10 times (i.e. 20mg/kg BW) of the recommended clinical dose when administered adequate ventilatory support (intermittent positive pressure ventilation -IPPV)2
In an acute tolerance study all cats survived IV injection of Alfaxan® at 5 times (i.e. 25mg/kg BW) of the recommended clinical dose when administered adequate ventilatory support (intermittent positive pressure ventilation – IPPV)3 |
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How is Alfaxan® metabolised in the body?
Alfaxan® is metabolised rapidly in the liver. Alfaxalone has a very short plasma elimination half-life in dogs and cats4,5
Alfaxalone is completely cleared from the body within a few hours after single administration6
Whether Alfaxan® is administered as a repeated bolus or as total intravenous anaesthesia (TIVA) as a continuous rate infusion, alfaxalone levels do not accumulate and recovery periods are not prolonged7. |
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Does Alfaxan® cause histamine release?
No, please see Figures 1 and 2 below for more information8. Normal histamine levels in dogs and cats are <1μmol/L and all the values in Figures 1 and 2 below are below 1μmol/L.
| Figure 1: Normal histamine levels in dogs and cats are <1µmol/L and all the values in Figures 1 and 2 below are below 1µmol/L. |
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Cats were dosed with Alfaxan® at a number of different doses (5, 10, 20 & 30mg/kg - up to 6 times the recommended clinical dose) and there was no significant rise in blood histamine levels.
| Figure 2: Blood histamine levels in dogs dosed with 30mg/kg of Alfaxan® as an IV bolus injection. |
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Dogs were dosed with Alfaxan® at 30mg/kg (15X the recommended dose) and there was no significant alteration in their blood histamine levels. |
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Can Alfaxan® be used in pregnancy?
The safety of Alfaxan® has not been established during pregnancy and lactation, in breeding animals or those intended for breeding in the future. 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. Alfaxan® should be used in pregnant animals according to the risk-benefit assessment performed by the veterinarian.
Please click here to download A Multi-Centre Clinical Trial Evaluating the Efficacy and Safety of Alfaxan® Administered to Bitches for Induction of Anaesthesia Prior to Caesarean Section abstract presented at the WSAVA 2008 congress. |
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How is Alfaxan® different to an
alfaxalone / alfadolone anaesthetic combination?
The only active ingredient in Alfaxan® is alfaxalone, not a combination of alfaxalone and alfadolone.
The previously available commercial preparation of alfaxalone / alfadolone also contained Cremaphor-EL which has been shown to cause histamine release in cats and dogs. Alfaxan® contains 2 alpha-hydroxypropyl-beta-cyclodextrin (HPBC) as the primary excipient, which does not cause histamine release.
Because of the above differences, Alfaxan® has different characteristics to an alfaxalone / alfadolone combination. The most noticeable differences are: Alfaxan® does not cause histamine release, provides smooth inductions, produces less “excitement” during recovery and has shorter duration of action. |
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