Elephant Formulary

© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International

Disclaimer: the information on this page is used entirely at the reader's discretion, and is made available on the express condition that no liability, expressed or implied, is accepted by the authors or publisher for the accuracy, content, or use thereof.


Atipamezole HCl

Elephant specific information, if available, is in blue.

Chemistry/Storage/Stability/Compatibility – An alpha2-adrenergic antagonist, atipamezole HCl injection should be stored at room temperature (15°-30°C) and protected from light.


Pharmacology – Atipamezole competitively inhibits alpha2-adrenergic receptors, thereby acting as a reversal agent for alpha2-adrenergic agonists (e.g., medetomidine). Net pharmacologic effects are to reduce sedation, decrease blood pressure, increase heart and respiratory rates, and re­duce the analgesic effects of alpha2-adrenergic agonists.


Uses/Indications – Atipamezole is labeled for use as a reversal agent for medetomidine. It potentially could be useful for reversal of other alpha2-adrenergic agonists as well (e.g., amitraz, xy­lazine).


Pharmacokinetics – After IM administration in the dog, peak plasma levels occur in about 10 minutes. Atipamezole is apparently metabolized in the liver to compounds that are eliminated in the urine. The drug has an average plasma elimination half life of about 2-3 hours.


Contraindications/Precautions/Reproductive Safety – While the manufacturer lists no absolute contraindications to the use of atipamezole, it states that the drug is not recommended in pregnant or lactating animals due to lack of data establishing safety in these animals. Caution should be used in administration of anesthetic agents to elderly or debilitated animals.


Adverse Effects/Warnings – Potential adverse effects include occasional vomiting, diarrhea, hypersalivation, tremors, and brief excitation/apprehensiveness.


Because reversal can occur rapidly, care should be exercised as animals emerging from sedation and analgesia may exhibit apprehensive or aggressive behaviors. After reversal, animals should be protected from falling. Additional analgesia (e.g., butorphanol) should be considered, particularly after painful procedures.


Overdosage – Dogs receiving up to 10X the listed dosage apparently tolerated the drug without major effects. When overdosed, dose related effects seen included panting, excitement, trembling, vomiting, soft or liquid feces, vasodilatation of sclera and some muscle injury at the IM injection site. Specific overdose therapy should generally not be necessary.


Drug Interactions – The manufacturer states that information on the use of atipamezole with other drugs is lacking, therefore, caution should be taken when using with other drugs (other than medetomidine).


Doses –



For reversal of medetomidine:

a)   Give IM an equal volume of Antisedan® as Domitor® is administered (ml per ml). The actual concentration of Antisedan® will be 5X that of Domitor®, as Antisedan® is 5 mg/ml versus Domitor®’s 1 mg/ml. (Package Insert; Antisedan®—Pfizer)

b) As above, but may give IV as well as IM. If it has been at least 45 minutes since medetomidine was given, may give atipamezole at half the volume of medetomidine if administered IV. If after 10-15 minutes an IM dose of atipamezole has not seemed to reverse the effects of medetomidine, an additional dose of atipamezole at 1/2 the volume of the medetomidine dose may be given. (McGrath and Ko 1997b)


For treatment of amitraz toxicity:

a) 50 mcg/kg IM (Hugnet, Buronrosse et al. 1996)



a) 1 mg atipamezole for every 8-12 mg xylazine will result in quick reversal in Asian

elephants (Cheeran, et.al. 2002).


b) 5-10 mg atipamezole injected IM or slow IV will reverse 100  mg xylazine (Rietschel

et.al. 2001).


c) 8-14 µg/kg atipamezole was given to partially reverse xylazine (33-72 µg/kg) to achieve standing sedation with responsiveness to voice commands in a 5000 kg male Asian elephant sedated on 3 occasions for treatment of a foot abscess (Honeyman et.al. 1998).


d) Atipamezole effectively reverses medetomidine sedation at doses of 200 mcg/kg body weight. Note that this is a general (i.e. not elephant specific dose). (Lance, 1991).


Elephant References:

a) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K. 2002. Tranquilization and translocation of elephants. Journal of Indian Veterinary Association Kerala 7:(3):42-46  

b) Rietschel,W., Hildebrandt,T., Goritz,F., and Ratanakorn,P.  2001. Sedation of Thai Working Elephants with Xylazine and Atipamezole as a Reversal.  A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001. Pages: 121-123

c) Honeyman,V.L.Cooper, R.M., Black, S.R. 1998. A protected contact approach to anesthesia and medical management of an Asian elephant (Elephas maximus).  Proceedings AAZV and AAWV Joint Conference. Pages: 338-341

d) Lance,W.R. 1991.  New pharmaceutical tools for the 1990’s. Proceedings of the American Association of Zoo Veterinarians 354-359

Monitoring Parameters – Level of sedation and analgesia; heart rate; body temperature


Client Information – Atipamezole should be administered by veterinary professionals only. Clients should be informed that occasionally vomiting, diarrhea, hypersalivation, excitation and tremors may be seen after atipamezole administration. Should these be severe or persist after leaving the clinic, clients should contact the veterinarian.


Dosage Forms/Preparations/FDA Approval Status  –


Veterinary-Approved Products:

Atipamezole HCl for Injection 5 mg/ml in 10 ml multidose vials; Antisedan® ; (Pfizer); (Rx) Approved for use in dogs.


Human-Approved Products: None