Pharmacodynamic Properties

Summary of Action

A positive allosteric modulator on GABA-A receptors and, at high concentrations, as a direct agonist of the GABA-A receptor. Alfaxalone has limited analgesic properties at clinical doses.

Mechanism of Action

The primary mechanism for Alfaxalone's anaesthetic action is the modulation of neuronal cell-membrane chloride-ion transport induced by its binding to GABA cell surface receptors.

Summary of Applications

Alfaxalone (alfaxalone or alfaxalone) is a neuroactive steroid, general anaesthetic induction agent, injectable anaesthetic, multimodal anaesthesia component, and animal sedative.

Veterinary Applications

Authorised Species: Alfaxalone is used in veterinary practice and is licensed for use in rabbits, dogs and cats.
Unauthorised Species: Alfaxalone is legally marketed as an unapproved agent in specific countries for a range of minor species excluding any food‑producing species including captive reptiles, captive amphibians, ornamental fish, including species used in research such as the zebrafish, pet birds in the orders Psittaciformes, Passeriformes, and Columbiformes, non‑human primates, captive rodents, captive mustelids, captive marsupials non‑human primates and captive minor species ungulates.

Pharmacokinetic Properties

Absorption

Alfaxalone can be injected intramuscularly, directly into a vein or intravenously via constant-rate infusion.
Inefficient when administered by the intramuscular route compared to the intravenous route.
Used with success by the intraosseous route in small reptiles, with some mild injection pain during induction.

Biotransformation

Hepatic: In vitro cat and dog hepatocyte studies show Alfaxalone undergoes Phase I (cytochrome P450 dependent) and Phase II (conjugation dependent) metabolism.
Phase I: Both cats and dogs from the same five Phase I Alfaxalone metabolites.
Phase II: Phase II metabolites observed in cats are Alexalone sulphate and Alexalone glucuronide, while Alexalone glucuronide is observed in dogs.

Elimination

Mixed Routes: Alfaxalone metabolites are eliminated from rabbits, dogs, and cats by the hepatic, faecal, and renal routes, which are expected to be similar in other species. In dogs and cats, the elimination of Alfaxalone demonstrates non-linear (dose-dependent) pharmacokinetics.

Half-Life

Feline: Alfaxalone's mean terminal plasma elimination half-life in cats is approximately 45 minutes for a 5 mg/kg dose. Mean plasma clearance for a 5 mg/kg dose is 25.1 ± 7.6 ml/kg/minute.
Canine: Alfaxalone's mean terminal plasma elimination half-life in dogs is approximately 25 minutes for a 2 mg/kg dose. Plasma clearance for a 2 mg/kg dose is 59.4 ± 12.9 ml/kg/minute.

Precautions

Adverse Effects

The most common side effects are dose-dependent but transient hypotension (15 min), hypoventilation, and apnea.

Anaphylaxis/Hypersensitivity
Apnea
Cardiorespiratory depression
Excitement
Hepatopathy
Hypotension
Hypothermia
Neonates
Pain

Contraindications

Inadequate Facilities and Support: (Intubation IPPV o2 supply thermal support

Reproductive Safety

Pregnancy: Caesarians
Lactation: No Data; Only use if potential maternal benefits outweigh potential offspring risks.
Fertility: No data located

Interactions

CNS depressants: These potentiate Alfaxan's CNS depressant effects, necessitating a reduced alfaxalone dose and/or cessation of further administration when the required depth of anaesthesia has been reached.

The authorised UK product has been demonstrated to be safe when used in combination with the following premedicant classes:

Phenothiazines (Acepromazine)
Anticholinergic agents (Atropine)
Benzodiazepines (Diazepam, Midazolam)
Alpha-2-adrenoceptor agonists (Xylazine, Medetomidine)
Opiates (Methadone, Morphine, Butorphanol, Buprenorphine)
NSAIDs (Carprofen, Meloxicam)

Overdose:

Presenting Signs: Hypoventilation Apnoea Hypotension
Clinical Response: Extended cardiorespiratory and thermal support.

Availability

Popular Formulations

Summary Statement

Specifics

Identifiers

Systematic Name: 11-oxo-3α,5α-tetrahydroprogesterone, 5α-pregnan-3α-ol-11,20-dione, or 3α-hydroxy-5α-pregnane-11,20-dione; 5alpha-Pregnan-3alpha-ol-11,20-dione; Alfaxalonum [INN-Latin]
Formula: C21-H32-O3
Pharmacotherapeutic Group: Anaesthetics - Alphaxolone is a corticosteroid hormone.
ATC vet code: QN01AX05
ATC code: N01AX05

Resources

Zotero Group: https://www.zotero.org/groups/4617706/formulary_alfaxalone

Bibliography

Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging [WWW Document], n.d. https://doi.org/10.1177/2055116916647740
Bradley, M.P., Doerning, C.M., Nowland, M.H., Lester, P.A., 2019. Intramuscular Administration of Alfaxalone Alone and in Combination for Sedation and Anesthesia of Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 58, 216–222. https://doi.org/10.30802/AALAS-JAALAS-18-000078
Chiu, K.W., Robson, S., Devi, J.L., Woodward, A., Whittem, T., 2016. The cardiopulmonary effects and quality of anesthesia after induction with alfaxalone in 2-hydroxypropyl-β-cyclodextrin in dogs and cats: a systematic review. Journal of Veterinary Pharmacology and Therapeutics 39, 525–538. https://doi.org/10.1111/jvp.12312
Harrison, N.L., Simmonds, M.A., 1984. Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Research 323, 287–292. https://doi.org/10.1016/0006-8993(84)90299-3
Miziak, B., Chrościńska-Krawczyk, M., Czuczwar, S.J., 2020. Neurosteroids and Seizure Activity. Front Endocrinol (Lausanne) 11, 541802. https://doi.org/10.3389/fendo.2020.541802
Shilo-Benjamini, Y., Pe’er, O., Abu Ahmad, W., Ofri, R., 2023. Effect of anesthetic induction with propofol, alfaxalone or ketamine on intraocular pressure in cats: a randomized masked clinical investigation. Veterinary Anaesthesia and Analgesia 50, 63–71. https://doi.org/10.1016/j.vaa.2022.11.005
Warne, L.N., Beths, T., Whittem, T., Carter, J.E., Bauquier, S.H., 2015. A review of the pharmacology and clinical application of alfaxalone in cats. The Veterinary Journal 203, 141–148. https://doi.org/10.1016/j.tvjl.2014.12.011

Alfaxalone