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Alfaxan: Information You Need!

By Marc Raffe, DVM, MS, DACVECC, DACVAA

Providing practical case management advice

to veterinarians with challenging cases

Anesthesia Consulting will be limited to 24-hour email turn-around only May 17-20, June 6-10, and June 23-29, 2019



BACKGROUND:
Alfaxan is the commercial name for alfaxalone, also known as alphaxalone or alphaxolone.   Molecularly, Alfaxan is a progesterone derivative that exhibits general anesthetic properties.   Alfaxalone is not a new drug, it was originally introduced in the 1970s in a mixture with alfadolone. The brand name for this combination in the veterinary market was Saffan®. Saffan was withdrawn from the market because of severe adverse effects characterized by histamine release and anaphylactic reactions which were caused by the drug carrier Cremophor EL®, a castor oil derivate. Alfaxan is a water soluble formulation. Water solubility is achieved by binding the alfaxalone molecule to cyclodextrin.   Alfaxan’s anesthetic action is due to binding to GABA-receptors. Alfaxalone binds to a different region of this receptor than the benzodiazepines. These benzodiazepine-insensitive GABAA receptors are responsible for its anesthetic activity. This allows Alfaxan to be used with benzodiazepine class tranquilizers such as diazepam or midazolam. 

Based on its properties, Alfaxan is considered to be a “sedative-hypnotic” class drug.  Other members of this class include propofol and etomidate.  In general, its clinical use and properties can be compared to propofol. Unlike propofol, Alfaxan has little or no cardiovascular effects when given in the normal dosage. At dosages of 20 mg/kg or more, cardiac output is reduced but this is well above the standard clinical dose. Respiratory depression may be noted following administration, the characteristics and magnitude are similar to propofol. In unpremedicated patients, tonic-clonic muscle activity characterized by twitches and shaking can be noted.  This feature has also been reported with propofol and etomidate when used without premedication.   As with other sedative-hypnotic drugs, there is controversy regarding whether Alfaxan has analgesic properties. Based on current experience,  Alfaxan should not be considered a significant analgesic.

Following administration, Alfaxan is rapidly metabolized by the liver and does not cause histamine release. It has a very short plasma elimination half-life in dogs and cats (23-32 minutes). Because of its short half-life which is similar to propofol, Alfaxan is suitable for repeated bolus injections or a continuous rate infusion (CRI). Unlike propofol, Alfaxan does not show potential adverse effects when dosed repeatedly in close succession or as a longer duration CRI. 


Alfaxan® can be safely combined with premedicants (xylazine, (dex)medetomidine, acepromazine, diazepam, midazolam), opioids (morphine, methadone, hydromorphone, butorphanol, nalbuphine, buprenorphine, fentanyl), and NSAIDs in the same patient.   It is not currently known what effect, if any, occurs when drugs are mixed in the same syringe.  

Alfaxan can be effectively delivered by either IV or IM route in both cats and dogs. In the US, it is labeled only for IV administration.  In other countries, Alfaxan has been licensed for IM injection.  It is not painful and has a quick onset of action following IM administration. Having access to this delivery route option is a major advantage of Alfaxan over propofol. In larger dogs, IM injection volume can be significant. For this reason, injection volume is limited to 0.5 mg/kg/injection site.

As with all anesthetic induction drugs, there are precautions with intravenous administration.   Induction doses of Alfaxan should be given "to effect".  A period of apnea is commonly seen; however, the incidence of apnea appears to be lower than that seen with propofol.  Disorientation (dysphoria)  may be noted on recovery when Alfaxan is  used as a sole agent due to its rapid elimination. Use of premeds will reduce or eliminate recovery dysphoria.  Hypersensitivity to external-stimuli has been reported during the recovery period in cats.  To avoid this event, recovery should be in a quiet, darkened room.

After the Alfaxan vial is opened, it has a shelf life of 6 hours unless transferred into sterile syringes for storage.  Refrigeration is recommended following syringe transfer.  Verbal conversations with Jurox technical staff indicate that storage is safe for 3 days following transfer to sterile syringes.  Microbial growth is possible after 3 days based on internal manufacturer studies in which Alfaxan was inoculated with bacteria. 

Alfaxan may be used for anesthesia induction in the dog or cat as follows (all doses are IV):


Dogs:   

              Unpremedicated: 1.5 – 4.5 mg/kg

                Premedication with opioid plus benzodiazepine tranquilizer:  1.2-5 mg/kg

                Premedication with opioid plus acepromazine: 0.6-3.5 mg/kg

                Premedication with alpha-2 agonist: 0.2-2 mg/kg


Cats:     
                Unpremedicated: 2 – 9 mg/kg IV 
                Opioid plus acepromazine: 1.1-10.8 mg/kg
                Alpha-2 agonist: 1-5 mg/kg


Intravenous induction is generally “to effect” and titrated to allow endotracheal intubation. Because of its minimal influence on cardiac output, alfaxalone can be used in compromised/injured patients.

SEDATION PROTOCOLS:

In overseas markets, Alfaxan is also indicated for parenteral sedation protocols.  For this indication, alfaxalone should not be used alone; alfaxalone is combined with tranquilizer, opioid, alpha-2 adrenergic or dissociative class drugs.  In these protocols, alfaxalone is being used as a sedative (similar to treating a patient with low doses of ketamine IM). Following administration, drug effect typically peaks in 5 minutes and, in the dog, the sedation period is quite short; you need to proceed with catheter placement quickly and efficiently.

Key Sedation Points in Dogs


Do not give alfaxalone alone, combine it with midazolam for ultrashort sedation or opioids/alpha-2 drugs for extended sedation.  Alfaxalone should NOT be used to sedate an aggressive and otherwise healthy dog.
 • Due to the volume needed, IM administration should be limited to smaller dogs (< 10 kg). A maximum volume of 0.5 ml/kg per injection site is recommended.
 • Sedation will be brief (5-10 min) but will provide time to establish an IV access, draw a blood sample or take an X-ray.
• Dysphoric recovery from IM sedation may require additional drugs to “smooth” the recovery period.



 Sedation protocol for alfaxalone /midazolam in dog and cat

2 – 4 mg/kg Alfaxan + 0.3 mg/kg midazolam IM
Anesthesia may be extended by redosing Alfaxan.  The package insert provides guidance on additional incremental IV dosing to extend effect.  Dose is titrated to patient need and dependent on the type and clinical effect of other anesthetic class drugs resident in the patient. As noted above, significant reduction in dose is noted high level sedative drugs represented by  (dex)medetomidine and opioids are used.  A continuous IV infusion (CRI) may also be used to extend the duration of action.  CRI dosing is as follows:

Maintenance CRI
     Dogs:        4 – 7 mg/kg/hr IV
     Cats:         5 – 8 mg / kg / hr IV

SPECIAL NOTES:


• Alfaxalone has no effects on neonates when used as an induction agent for caesarian section.

 • Alfaxalone can replace etomidate as an induction agent for high risk patients.

• Alfaxalone is a suitable agent for sighthound anesthesia

 • For use in smaller patients it may be best to dilute the alfaxalone 10 mg/ml to 5 mg/ml, using equal volumes of Lactated Ringers solution or 0.9% NaCl. This allows for more precise dosing and adjustments.

• Alfaxan® contains no preservatives. Opened bottles should be handled with caution as noted above.   USA labeling indicates that open vial contents should be discarded within 6 hrs.  Transfilling into sterile syringes stored at refrigerated conditions will extend the shelf life until three days as noted above.  It is interesting that labeling in New Zealand and Australia states that Alfaxan should be store below 30°C.  Contents of opened vials should preferably be used within 24 hours, but may be stored if necessary at 4°C for up to 7 days provided contamination is avoided. Do not use opened vials if the solution is not clear, colorless and free from particulate matter.