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What is Alfaxan®?

Alfaxan® consists of the active ingredient alfaxalone in an aqueous solution with a pH of 6.5-7, and is registered for use in dogs and cats for both the induction and maintenance of anaesthesia. Alfaxalone is a neuroactive steroid molecule, with central effects. Despite being an analogue of progesterone, Alfaxalone does not bind to sex hormone, glucocorticoid, or mineralocorticoid receptors. Jurox and Ricera, An in vitro study evaluating the binding of alfaxalone to various nuclear receptors (Ricerca Study No. AA94464).Records in House, 2010  

Features

References to support the above claims Comparison of pain on injection during induction of anaesthesia with alfaxalone and two formulations of propofol in dogs, Michou et al, Vet Anaesth Anal A comparison of anaesthetic recoveries in cats following induction with either alfaxalone or ketamine and diazepam, Gieseg et al, 2013, NZVJ 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 Psatha, E., et al., Clinical efficacy and cardiorespiratory effects of alfaxalone, or diazepam/fentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk.Vet Anaesth Analg, 2011. 38: p. 24-36. Martinez Taboada, F. and P.J. Murison, Induction of anaesthesia with alfaxalone or propofol before isoflurane maintenance in cats.Veterinary Record, 2010. 167(3): p. 85-89 Maddern, K., et al., Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog. Veterinary Anaesthesia and Analgesia, 2010. 37(1): p. 7-13. Heit, M.C., et al. Cardiovascular and respiratory safety of Alfaxan®CD RTU in cats premedicated with acepromazine, medetomidine, midazolam or butorphanol.in ACVIM.2004 Pasloske, K. and T. Whittem, JX9604.07-H004 A target animal safety study in cats after administration of Alfaxan® -CD RTU as single, repeated injections on days 0, 2, and 5 at dosages of 5, 15 or 25 mg/kg.2004, On File at Jurox Whittem, T. and K. Pasloske, RD9604.03-H005 Eight day target animal safety study of intravenous Alfaxan® CD RTU in dogs administered every other day.2004, Jurox Pty Limited 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. Heit, M.C., et al. Safety and efficacy of Alfaxan® CD RTU Administered once to cats subcutaneously at 10 mg/kg.in ACVIM. 2004 Muir, W., et al., Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs.Vet Anaesth Analg, 2008. 35(6): p. 451-462. 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.

Safety

Alfaxan® has a very wide safety margin.

Therapeutic index: 

Acute tolerance to overdose of Alfaxan® at 5 times the registered dose (i.e. 25 mg/kg) in cats and 10 times the registered dose  (i.e. 20 mg/kg) in dogs was demonstrated where animals required only ventilation to allow recovery with no residual effects. Muir, W., et al., Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs.Vet Anaesth Analg, 2008. 35(6): p. 451-462. 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.

Repeated Dosing

Repeated overdosing with Alfaxan® - 5 times the registered dose every 48 hours over a six day period caused no adverse effects. Pasloske, K. and T. Whittem, JX9604.07-H004 A target animal safety study in cats after administration of Alfaxan® -CD RTU as single, repeated injections on days 0, 2, and 5 at dosages of 5, 15 or 25 mg/kg.2004, On File at Jurox Whittem, T. and K. Pasloske, RD9604.03-H005 Eight day target animal safety study of intravenous Alfaxan® CD RTU in dogs administered every other day.2004, Jurox Pty Limited

Extra-vascular safety

Alfaxan® does not cause tissue irritation should accidental peri-vascular or subcutaneous injection occur. Heit, M.C., et al. Safety and efficacy of Alfaxan® CD RTU Administered once to cats subcutaneously at 10 mg/kg.in ACVIM. 2004

Paediatric

Alfaxan® can be safely used in puppies and kittens from 12 weeks of age Zaki, S., K. Ticehurst, and Y. Miyaki, Clinical evaluation of Alfaxan®-CD(R) as an intravenous anaesthetic in young cats.Aust Vet J, 2009. 87(3): p. 82-7 O’Hagan, B., et al., Clinical evaluation of alfaxalone as an anaesthetic induction agent in dogs less than 12 weeks of age.Australian Veterinary Journal, 2012. 90(9): p. 346-50 O’Hagan, B., et al., Clinical evaluation of alfaxalone as an anaesthetic induction agent in cats less than 12 weeks of age.Australian Veterinary Journal, 2012. 90(10): p. 395-401

C-section

Alfaxan® can safely be used prior to canine caesarean section. Induction of anaesthesia for canine caesarean section with alfaxalone, Reproductive Biology, 2013 Metcalfe, S., et al. A multi-centre clinical trial evaluating the efficacy and safety of Alfaxan® administered to bitches for induction of anaesthesia prior to caesarean sectionin 33 rd World Small Animal Congress.2008. Dublin, Ireland: WSAVA/FECAVA

Sighthounds

Alfaxan® can be safely used in greyhounds, salukis, whippets, etc. Pasloske, K., et al., Plasma pharmacokinetics of alfaxalone in both premedicated and unpremedicated Greyhound dogs after single, intravenous administration of Alfaxan® at a clinical dose.Journal of Veterinary Pharmacology and Therapeutics, 2009. 32: p. 510-513.

Mode of Action

Alfaxalone induces anaesthesia through activity at the gamma amino butyric acid sub-type A receptor (GABAA) present on cells in the Central Nervous System (CNS) . GABA is a major inhibitory neurotransmitter in the CNS. Roth, F.C. and A. Draguhn, GABA Metabolism and Transport: Effects on Synaptic Efficacy.Neural Plasticity, 2012. 2012. Alfaxalone enhances the effects of GABA at the GABAA receptors resulting in opening of channels into the cells and an influx of chloride ions. This causes hyperpolarisation of the cells and inhibition of neural impulse transmission.

History

Steroids were first recognised to have anaesthetic properties in the 1940s. Numerous investigations and iterations of steroid molecular modification have occurred over time in the attempt to create useful formulations of neurosteroid molecules.

The first commercially manufactured formulation of neurosteroids was widely used through the 1970s and 1980s in both human and veterinary anaesthesia. Neurosteroid anaesthesia was recognised for its excellent anaesthetic properties and minimal effects on cardiovascular function. However it was also recognised that the excipient used to solubilise that formulation, Cremophor® EL (registered trademark of BASF), caused systemic histamine release.

In the 1990s it was found that alfaxalone could be solubilised in aqueous solution by first complexing it to large sugar molecules known as cyclodextrins. Brewster, M.E., K.S. Estes, and N. Bodor, An intravenous toxicity study of 2-hydroxypropyl- β-cyclodextrin, a useful drug solubilizer, in rats and monkeys.Int J Pharm, 1990. 59: p. 231-243. Brewster, M.E., K.S. Estes, and N. Bodor, Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins.J Parenter Sci Technol, 1989. 43(6): p. 262-5

Alfaxalone
Cyclodextrin

Pharmacodynamics

Dogs

Cats

Fair Balance Statement

This website does not include all the information needed to use Alfaxan® safely and effectively. See full package insert for complete prescribing information. Alfaxan® is a general anesthetic agent for dogs and cats. Attention to safe anesthetic practices including thorough patient evaluation, ability to secure an airway and ability to support cardiovascular and respiratory function should be a priority when using Alfaxan®.