Alfaxalone

Neuroactive steroid IV anesthetic. GABA-A potentiation via a different binding site than propofol. Wider therapeutic margin and less cardiovascular depression than propofol; labeled IM/SC route in cats. No analgesia.

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Clinical background

Alfaxalone is a neuroactive steroid IV anesthetic that has been the second-most-common induction agent in small animal practice since its US launch in 2014 (after propofol). Its key advantages over propofol are a wider therapeutic margin, less cardiovascular depression at clinically equivalent depths, and a labeled IM/SC route for cats, making it the go-to induction agent in patients where propofol’s hemodynamic profile is concerning, where IM induction is preferred (fractious cats, lack of IV access), or where repeated daily induction is needed.

Pharmacology

Alfaxalone is a synthetic neurosteroid that potentiates GABA-A-mediated chloride conductance in the CNS, producing dose-dependent unconsciousness through the same final pathway as propofol but at a different binding site on the receptor. Onset after IV bolus is 30–60 seconds; clinical duration after a single induction dose is 5–10 minutes in dogs and 10–20 minutes in cats.

Hepatic metabolism is rapid in dogs, the cyclodextrin-solubilized formulation (Alfaxan Multidose) does not appear to accumulate clinically over typical induction-and-maintenance courses. Cats clear alfaxalone more slowly than dogs, which means recoveries are longer and CRI infusions accumulate more readily.

The cyclodextrin vehicle (HPCD) is what enables the drug to be water-soluble. Earlier formulations (Saffan, used in Australia/EU) used a different solubilizer (Cremophor EL) that caused histamine release in dogs, this is not an issue with the current HPCD-based product.

Indications

• Induction for general anesthesia: both dogs and cats; the labeled use
• Sedation for short procedures when combined with an opioid and/or sedative
• TIVA (total IV anesthesia): feasible in dogs and cats as a CRI; the cyclodextrin vehicle tolerates infusion better than propofol’s lipid emulsion does over hours
• IM induction in cats: labeled extra-label indication; useful for fractious cats where IV access is difficult
• Cesarean section anesthesia in dogs: the cardiovascular profile is more favorable than propofol or thiopental for the dam, with comparable neonatal outcomes
• Patients with significant cardiovascular disease where the lower SVR-dropping effect of alfaxalone is preferred over propofol

Dosing

Doses depend heavily on whether the patient has been premedicated. The InfusionFox calculator distinguishes premedicated and unpremedicated dose ranges directly.

• Dogs, premedicated induction: 1.1–4.5 mg/kg IV (default 4.5)
• Dogs, unpremedicated induction: 2.0–4.0 mg/kg IV (titrated)
• Cats, premedicated induction: 2.3–9.7 mg/kg IV
• Cats, unpremedicated induction: higher doses needed; titrate slowly

Always titrate over 60–90 seconds rather than giving as a rapid push. Apnea is dose- and rate-dependent: faster bolus produces more apnea even at the same total dose. Have intubation equipment, oxygen, and assisted ventilation immediately available before any induction.

For TIVA / CRI use: 6–8 mg/kg/hr in dogs, lower in cats due to slower clearance.

Adverse effects

• Apnea: common at induction; expected and managed by intubation and ventilation. Less profound than propofol at equivalent depths but not absent.
• Hypotension: present but generally less marked than with propofol. Cardiac output and SVR are better preserved.
• Excitatory recoveries: particularly in cats and in patients without adequate sedative premedication. Manifests as paddling, vocalization, or rough emergence. The mechanism is suspected to involve disinhibition during the recovery phase. Mitigation: ensure adequate premedication (alpha-2 agonist + opioid is best), recover in a quiet, dimly lit environment, and avoid stimulation during emergence.
• Hyperthermia in cats: described in association with alfaxalone use, similar to opioid-related hyperthermia. Monitor temperature.
• No analgesia: alfaxalone provides anesthesia and immobilization but no analgesic activity. Multimodal premedication is essential for any procedure expected to cause pain.

Drug interactions

• CNS depressants: additive sedation and respiratory depression with opioids, benzodiazepines, alpha-2 agonists, acepromazine, and inhalant anesthetics. Doses of each should be reduced.
• Compatibility: the cyclodextrin formulation is generally compatible with most common drugs and crystalloids; refer to current product literature for specific Y-site compatibility.

Storage and product notes

The current US product (Alfaxan Multidose) is preserved with chlorocresol and may be used for up to 28 days after first puncture (per product label). The original single-dose formulation (Alfaxan) had no preservative and required immediate use. Confirm which formulation you have before drawing up.

Sources

• Plumb’s Veterinary Drugs, alfaxalone monograph.
• Suarez MA et al: Cardiopulmonary effects of alfaxalone in dogs. Vet Anaesth Analg 2012.
• Whittem T et al: The pharmacokinetics and pharmacodynamics of alfaxalone in cats. J Vet Pharmacol Ther 2008.