Alfaxalone

Neuroactive steroid anesthetic Anesthetic (injectable)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 2-5 mg/kg (induction); 0.1-0.2 mg/kg/min (maintenance infusion) Single dose for induction; continuous infusion for maintenance Duration: Induction: single dose; Maintenance: as needed
Notes: Premedication with an opioid and/or sedative may reduce the dose required. Dose to effect.
Cat IV 5-10 mg/kg (induction); 0.1-0.2 mg/kg/min (maintenance infusion) Single dose for induction; continuous infusion for maintenance Duration: Induction: single dose; Maintenance: as needed
Notes: Cats may require higher doses than dogs. Premedication can reduce dose.
Cat IM 10-15 mg/kg (for sedation or induction in kittens or difficult cats) Single dose Duration: Sedation: 15-30 minutes; Induction: 5-10 minutes
Notes: IM administration is useful for fractious cats. Onset is slower and recovery may be prolonged.
Horse IV 0.5-1.0 mg/kg (induction); 0.02-0.05 mg/kg/min (maintenance infusion) Single dose for induction; continuous infusion for maintenance Duration: Induction: single dose; Maintenance: as needed
Notes: Often used with guaifenesin or other agents for TIVA. Dose to effect.
Cattle IV 2-4 mg/kg (induction) Single dose Duration: Induction: single dose
Notes: Off-label in many countries. Use with caution in neonates and debilitated animals.
Small Ruminants (sheep, goats) IV 2-5 mg/kg (induction) Single dose Duration: Induction: single dose
Notes: Off-label. May cause respiratory depression at higher doses.
Rabbit IV 5-10 mg/kg (induction) Single dose Duration: Induction: single dose
Notes: May be used IM at 10-15 mg/kg for sedation. Rabbits are sensitive to stress; use with premedication.
Bird (e.g., psittacines) IV 5-10 mg/kg (induction) Single dose Duration: Induction: single dose
Notes: Off-label. Use with caution; birds are sensitive to respiratory depression.

Clinical Indications & Species Uses

General Indications
  • Injectable anesthesia for short procedures
  • Induction prior to inhalant anesthesia
Dog (Canine)
  • Induction and maintenance of anesthesia
  • Sedation for minor procedures
  • Co-induction with other anesthetics
Cat (Feline)
  • Induction and maintenance of anesthesia
  • Sedation for minor procedures
  • Co-induction with other anesthetics
Horse (Equine)
  • Induction of anesthesia
  • Maintenance of anesthesia (as part of total intravenous anesthesia, TIVA)
Cattle (Bovine)
  • Induction of anesthesia
  • Sedation for minor procedures (off-label in some countries)
Small Ruminants (Sheep / Goat)
  • Induction of anesthesia
  • Sedation for minor procedures (off-label)
Rabbit & Small Mammals
  • Induction and maintenance of anesthesia
  • Sedation for minor procedures
Avian & Poultry
  • Induction and maintenance of anesthesia (off-label in many countries)
Exotic & Other Species
  • Induction and maintenance of anesthesia in small mammals (e.g., ferrets, guinea pigs) and reptiles (off-label)

Pharmacology & Mechanism of Action

Drug Class: Neuroactive steroid anesthetic | Pharmacological Group: Anesthetic (injectable)

Mechanism of Action: Alfaxalone is a synthetic neuroactive steroid that produces anesthesia by modulating the gamma-aminobutyric acid type A (GABA-A) receptor complex. It binds to a distinct site on the receptor, enhancing the effect of GABA, the primary inhibitory neurotransmitter in the central nervous system. This leads to increased chloride ion influx into neurons, hyperpolarization, and inhibition of neuronal firing, resulting in dose-dependent sedation, hypnosis, and anesthesia. Unlike propofol, alfaxalone does not appear to have significant cardiovascular or respiratory depressant effects at clinical doses, and it has a wide safety margin.

Pharmacodynamics: Alfaxalone produces rapid induction of anesthesia with good muscle relaxation and minimal excitation. It has a dose-dependent effect on the central nervous system, with increasing doses leading to deeper anesthesia. It has a short duration of action due to rapid redistribution and metabolism. It does not possess analgesic properties, so it is often used in combination with analgesics for painful procedures. It has minimal effects on cardiac output and blood pressure, and respiratory depression is dose-dependent but less pronounced than with propofol. It also has antiemetic properties and does not cause histamine release.

⚡ Pharmacokinetics Summary

Absorption: Alfaxalone is administered intravenously (IV) or intramuscularly (IM). After IV administration, onset of anesthesia is rapid (within 30-60 seconds). After IM administration, absorption is slower, with onset of sedation/anesthesia occurring within 5-10 minutes, depending on the species and dose. Bioavailability after IM injection is variable but generally high in cats and dogs.
Distribution: Alfaxalone is highly lipophilic and rapidly distributes to well-perfused tissues, including the brain, resulting in rapid onset of anesthesia. It has a large volume of distribution. It is moderately bound to plasma proteins (approximately 40-50% in dogs and cats).
Metabolism: Alfaxalone is primarily metabolized in the liver via reduction and conjugation (glucuronidation). The metabolites are inactive. Hepatic metabolism is rapid, but the drug's short duration of action is mainly due to redistribution from the brain to other tissues.
Excretion: Metabolites are excreted primarily in the urine (approximately 60-70%) and feces (30-40%). A small fraction is excreted unchanged. In dogs, the elimination half-life is approximately 24-45 minutes; in cats, it is slightly longer, around 30-60 minutes.
Half-Life: Dogs: 24-45 minutes; Cats: 30-60 minutes; Horses: approximately 30 minutes; Rabbits: approximately 20-30 minutes.
Bioavailability: IV: 100%; IM: variable, approximately 70-90% in cats and dogs.
Protein Binding: Approximately 40-50% in dogs and cats; lower in other species.

Available Formulations & Strengths

Injectable Solution 10 mg/mL in 10 mL and 20 mL vials (IV or IM)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to alfaxalone or any component of the formulation
  • Severe hepatic insufficiency (metabolism is hepatic)
  • Severe cardiovascular instability (though less than other agents, use with caution)
  • Pregnancy (unless benefits outweigh risks; safety not established)
  • Do not use in animals with a history of seizures (may lower seizure threshold in some cases)
Warnings & Clinical Precautions:
  • Use with caution in debilitated, geriatric, or pediatric animals; reduce dose.
  • Respiratory depression may occur, especially at higher doses; monitor ventilation and provide oxygen if needed.
  • Apnea may occur during induction; have intubation equipment and ventilatory support available.
  • Alfaxalone has no analgesic properties; use with appropriate analgesics for painful procedures.
  • Rapid IV injection may cause apnea; administer slowly to effect.
  • In cats, IM administration may cause pain at injection site and prolonged recovery.
  • Use in food animals is off-label in many countries; observe withdrawal times.
  • Do not mix with other drugs in the same syringe unless compatibility is known.
  • Use aseptic technique; discard unused portions after opening.

Adverse Effects & Reactions

Common:

  • Apnea (transient, especially with rapid IV injection)
  • Hypotension (mild, dose-dependent)
  • Respiratory depression (dose-dependent)
  • Excitement during recovery (especially in cats)
  • Pain on IM injection

Serious / Severe:

  • Severe respiratory depression or apnea
  • Cardiovascular collapse (rare)
  • Anaphylaxis (rare)
  • Seizures (rare, especially in animals with underlying seizure disorders)

Rare:

  • Pulmonary edema (reported in cats)
  • Hepatotoxicity (unlikely but possible with overdose)
  • Hyperthermia or hypothermia (due to altered thermoregulation)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other CNS depressants (e.g., opioids, benzodiazepines, phenothiazines, alpha-2 agonists) Additive sedative and respiratory depressant effects; reduce alfaxalone dose by 25-50% when used in combination. High
Inhalant anesthetics (e.g., isoflurane, sevoflurane) Additive anesthetic effects; reduce alfaxalone dose when used for induction prior to inhalant anesthesia. Moderate
Neuromuscular blocking agents Alfaxalone does not potentiate neuromuscular blockade, but concurrent use may require monitoring of anesthetic depth. Mild
Corticosteroids Potential for altered metabolism due to enzyme induction; clinical significance unclear. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Prolonged anesthesia
  • Severe respiratory depression or apnea
  • Hypotension
  • Bradycardia
  • Hypothermia
  • Coma

Emergency Treatment Protocol: There is no specific antidote. Treatment is supportive: maintain airway, provide oxygen and mechanical ventilation if necessary, administer IV fluids to support blood pressure, and use inotropic agents (e.g., dopamine) if severe hypotension occurs. Keep the animal warm and monitor vital signs until recovery. In cases of severe overdose, consider lipid emulsion therapy (though evidence is limited).

Food Animal Withdrawal Times

Alfaxalone is not approved for use in food animals in many countries. If used off-label, a withdrawal time of at least 24 hours for meat and milk is recommended, but local regulations should be consulted. No official withdrawal times are established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Protect from freezing. Do not use if solution is discolored or contains particulate matter. Use within 28 days of first puncture if stored at room temperature.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved by FDA for use in dogs and cats (Alfaxan®). Not approved for food animals.

Extra-Label (Off-Label) Use: In the US, alfaxalone is approved for use in dogs and cats. Extra-label use in other species is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) provided there is a valid veterinarian-client-patient relationship, and appropriate withdrawal times are observed for food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Alfaxalone is a versatile injectable anesthetic that provides smooth induction and recovery with minimal cardiovascular depression. It is particularly useful in cats and dogs, and increasingly used in exotic species. Because it lacks analgesic properties, it should be combined with opioids or other analgesics for painful procedures. Premedication with sedatives (e.g., dexmedetomidine, acepromazine) or opioids can reduce the required dose and improve anesthetic quality. Monitoring of respiratory rate, oxygen saturation, and blood pressure is essential during anesthesia. Recovery is generally rapid and excitement is less common than with propofol, but cats may exhibit some excitement if not adequately premedicated. Alfaxalone can be used for both induction and maintenance via continuous infusion, but total intravenous anesthesia (TIVA) requires careful monitoring. In food animals, use is off-label and withdrawal times must be considered. Always have emergency drugs and equipment available when using alfaxalone.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)