Alpha-2 Adrenergic Antagonist (Systemic Drug)
- Alpha-2 adrenergic antagonist; reverses the effects of agonists such as dexmedetomidine, medetomidine, and xylazine.
- No safety data on use in pregnant or lactating animals.
- May reverse effects rapidly, including analgesia; animals should be observed and protected from self-harm or causing harm to others.
- Adverse effects may include trembling, vomiting, diarrhea, hypersalivation or excitation.1
- Antisedan Pfizer: Atipamezole hydrochloride injection solution branded by Pfizer Animal Health.
- Atipamezole has also been researched in humans as a potential anti-Parkinsonian.
Atipamezole is labeled for use as a reversal agent for medetomidine and dexmedetomidine in order to reduce their sedative and analgesic effects. It potentially could be useful for reversal of other alpha-2 adrenergic agonists as well (eg, amitraz, xylazine, clonidine, tizanidine, brimonidine).1
Commonly used to treat horses and dogs. Extra-label use for other species.
Atipamezole competitively inhibits alpha-2 adrenergic receptors, thereby acting as a reversal agent for alpha-2 adrenergic agonists (eg, medetomidine). Net pharmacologic effects are to reduce sedation, decrease blood pressure, increase heart and respiratory rate, and reduce the analgesic effects of dexmedetomidine. Atipamezole will antagonize the diuretic action of xylazine in dogs1 and decrease medetomidine-induced tear production in cats 15 minutes after its administration.2 Atipamezole does not completely reverse the sedative and bradycardic effects in horses when administered 1 hour after sublingual detomidine gel.3
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 to 3 hours.
In horses after sublingual administration of detomidine gel, atipamezole has an average clearance and elimination half-life of 25 mL/kg/min and 53 minutes, respectively.4
Contraindications / Precautions:
While there are no absolute contraindications to the use of atipamezole listed, the drug is not recommended in pregnant or lactating animals due to the lack of data establishing safety. When used as a reversal agent (antidote) for alpha-2-agonist toxicity, effects of atipamezole effects may subside before nontoxic levels of the offending agent are reached; repeat dosing may be necessary.
Do not give IV to reptiles as profound hypotension can occur.1
Potential adverse effects include occasional vomiting, diarrhea, hypersalivation, tremors, and brief excitation or 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 (eg, opioids) should be considered, particularly after painful procedures.1
The manufacturer states that the drug is not recommended in pregnant or lactating animals or in animals intended for breeding due to lack of data establishing safety in these animals. No other data was noted.1
Dogs receiving up to 10 times the listed dosage apparently tolerated the drug without major effects. When overdosed, dose-related effects included panting, excitement, trembling, vomiting, soft or liquid feces, vasodilatation of sclera, and some muscle injury at the IM injection site. Specific overdose therapy is generally not necessary.1
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). The following drug interactions with atipamezole have either been reported or are theoretical in humans or animals and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.
- ALPHA-1 ADRENERGIC BLOCKERS (eg, prazosin): Atipamezole is a relatively specific alpha-2 blocker, but it can also partially block alpha-1 receptors, especially at high dosages, and reduce the effects of prazosin.
- ALPHA-2 ADRENERGIC AGONISTS (eg, detomidine, clonidine, brimonidine, xylazine, amitraz): Atipamezole can reduce the effects (toxic or therapeutic) of these agents.
- TILETAMINE/ZOLAZEPAM: Atipamezole may reduce the effects (toxic or therapeutic) of these agents.
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 reversal of the sedative or after leaving the clinic, clients should contact the veterinarian.1
Dogs - Reversal of dexmedetomidine or medetomidine in dogs (labeled dosage; FDA-approved): 3750 micrograms/m2 IM regardless of the route used for dexmedetomidine or medetomidine. Formulated so that the volume of injection is the same (mL for mL) as the recommended (labeled) dose of dexmedetomidine or medetomidine per body weight. The product label (package insert) has a detailed dosage chart that converts dog’s weight (in lb) to dosage in micrograms/kg and mLs.1
Reversal of dexmedetomidine or medetomidine (extra-label): 100 micrograms/kg IV or IO (intraosseous) as part of CPR to reverse alpha-2 agonists. Dosage is based on a 10 micrograms/kg dexmedetomidine dose. If a higher dose of dexmedetomidine was administered, increase this dose accordingly.5 Treatment of amitraz toxicity (extra-label): 50 micrograms/kg IM; doses may need to be repeated every 4 to 6 hours as the half-life of amitraz is longer than atipamezole in dogs.6
Cats - Reversal agent (extra-label):
a)Reversal of medetomidine, when used alone or in combination with other sedatives or analgesics: Use an equal volume IM of atipamezole as medetomidine was used in the combination.7
b)Reversal of dexmedetomidine or medetomidine: 100 micrograms/kg IV or IO as part of CPR to reverse alpha-2 agonists. Dosage is based on a 10 microgram/kg dexmedetomidine dosage. If a higher dose of dexmedetomidine was administered, increase this dose accordingly.5
c)Reversal of xylazine sedation (when xylazine is used as an emetic): 25 – 50 micrograms/kg IM or IV (slowly).8
a)Rabbits: For medetomidine reversal (extra-label): 0.5 mg/kg IM or SC; 0.25 mg/kg IV.9
b)Mice, Rats, Gerbils, Hamsters, Guinea Pigs: To reverse xylazine or medetomidine (extra-label): 0.1 – 1 mg/kg IM, IP, IV or SC.10
Horses - Reversal of alpha-2 adrenergic agonist (eg, amitraz, xylazine) toxicity (extra-label): 0.1 mg/kg IV has been suggested.9
Ruminants - Reversal agent for alpha-2 adrenergic agonists (eg, xylazine, detomidine); (extra-label):
a)Bovine, new world camelids, ovine and caprine species: 0.02 – 0.1 mg/kg IV to effect.11
b)Small ruminants, camelids: 0.1 – 0.2 mg/kg slow IV or IM; as a rule of thumb, if induction included ketamine or Telazol® do not reverse alpha-2 sooner than 30 and ideally 60 minutes after induction. This will allow enough of the ketamine or tiletamine to be metabolized.12,13
Birds - Reversal agent for alpha-2 adrenergic agonists (eg, xylazine, dexmedetomidine); (extra-label):
a)0.5 mg/kg IM.14
b)250 micrograms/kg intranasally has been reported in pigeons. Antagonism of side effects and sedation was observed, but complete recovery had not occurred after 10 minutes.15
Reptiles - Reversal agent for alpha-2 adrenergic agonists (extra-label): Reversal of all dosages ketamine/medetomidine combination (see Ketamine or Medetomidine monographs) with atipamezole is 4-5 times the medetomidine dose.16 Reversal may take longer (up to one hour) in reptiles than in other species; Do NOT give IV as profound hypotension can occur.17
Zoo, Exotic, Wildlife Species - Refer to specific references, including:
a) Zoo Animal and Wildlife Immobilization and Anesthesia. 2nd ed. West G, Heard D, Caulkett N, eds. Blackwell Publishing; 2014.
b) Handbook of Wildlife Chemical Immobilization. 3rd ed. Kreeger TJ, Arnemo JM. 2007.
c) Fowler’s Zoo and Wild Animal Medicine Current Therapy, vol 8. Miller RE, Fowler ME. Saunders; 2015.
d)Exotic Animal Formulary. 4th ed. Carpenter JW. Saunders; 2012e) The 2009 American Association of Zoo Veterinarian Proceedings by D. K. Fontenot also has several dosages listed for restraint, anesthesia, and analgesia for a variety of drugs for carnivores and primates.
1Plumb's Veterinary Drugs.
2Talukder MH, et al. Antagonistic Effects of Atipamezole and Yohimbine on Xylazine-Induced Diuresis in Healthy Dogs. J Vet Med Sci. 2009;71(5):539-548.
3Di Pietro S, et al. Effects of a medetomidine-ketamine combination on Schirmer tear test I results of clinically normal cats. Am J Vet Res. 2016;77(3):310-314.
4Knych HK, Stanley SD. Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse. Vet Anaesth Analg. 2014;41(1):36-47.
5Fletcher DJ, et al. Recover evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines. Journal of Veterinary Emergency and Critical Care. 2012;22.
6Hugnet C, et al. Toxicity and kinetics of amitraz in dogs. Am J Vet Res. 1996;57(10):1506-1510.
7Ko J. New anesthesia-analgesia injectable combinations in dogs and cats. Proceedings: ACVC 2005. 2005. Veterinary Information Network.
8Wells R. Toxins and Poisons. Western Veterinary Conference Proceedings 2012. 2012.
9Vella D. Rabbit General Anesthesia. Proceedings: AAVAC-UEP 2009. 2009. Veterinary Information Network
10Adamcak A, Otten B. Rodent Therapeutics. Vet Clin NA: Exotic Anim Pract. 2000;3:1(Jan):221-240.
11Haskell R. Development of a Small Ruminant Formulary. Proceedings: WVC 2005. 2005. Veterinary Information Network
12Snyder J. Small Ruminant Medicine & Surgery for Equine and Small Animal Practitioners I & II. Proceedings: WVC 2009. 2009. Veterinary Information Network
13Wolff P. Camelid Medicine. Proceedings: AAZV 2009. 2009. Veterinary Information Network
14Clyde V, Paul-Murphy J. Avian Analgesia. In: Bonagura J, ed. Kirk's Current Veterinary Therapy: XIII Small Animal Practice. Philadelphia: WB Saunders; 2000:1126-1128.
15Hornak S, et al. A preliminary trial of the sedation induced by intranasal administration of midazolam alone or in combination with dexmedetomidine and reversal by atipamezole for a short-term immobilization in pigeons. Vet Anaesth Analg. 2015;42(2):192-196.
16Heard D. Advances in Reptile Anesthesia. The North American Veterinary Conference 1999. 1999; Orlando.
17Mehler S. Anaesthesia and care of the reptile. Proceedings: BSAVA 2009. 2009. Veterinary Information Network.