New Warning About an Old Drug

Acepromazine (acepromazine maleate, acetylpromazine, ACE, ACP) is commonly used in veterinary medicine as a tranquilizer or pre-anesthetic agent. In 1996, the University of California at Davis issued a memo describing three Boxers suffering adverse reactions to acepromazine (respiratory arrest in one, and severe decreased heart rate in two), and suggesting that the drug be avoided in the Boxer breed. This memo confirmed anecdotal reports which had been circulating for years in various countries; a discussion on the Veterinary Information Network in April of 1996 included long acknowledgment of the breed’s sensitivity by vets in the US, Canada, the UK, Australia, and Greece. Many veterinarians took notice of the UCDavis memo, and veterinary textbooks and publications
began to include information on the breed’s sensitivity to, and cautions orr ecommendations for avoidance of, the drug in Boxers.

More than a decade later, however, some veterinarians still claim that they have never had a problem with acepromazine in Boxers, and a few insist on using it despite their clients’ requests to avoid it. While it is true that not all Boxers will experience an adverse reaction,
that is of little comfort to the owner who requested the drug not be used, gave in to the vet’s insistence that it was safe, and lost their Boxer as a result.

A common argument that vets use to refute the adverse effects of acepromazine in Boxers is that affected dogs must have an underlying heart condition. While this has never been studied, and may or may not be true, it is important to point out that in a breed that is prone to a heart condition which may not be detected except by necropsy, there is simply no way for a vet to know if the dog to which he’s about to administer acepromazine has
an underlying heart condition. Given some estimates that 50-80% of the breed is affected with ARVC, a vet who uses this rationale is taking quite a risk when he administers acepromazine to any Boxer.

Another justification vets give for acepromazine use in Boxers is that they give a low dose, so the risk is reduced. However, there are reports of Boxers collapsing even after very small doses of acepromazine. Some vets give an anticholinergic drug, such as atropine, in conjunction with acepromazine; this protocol may help prevent the bradycardiac effects of the drug, but there have been anecdotal reports of adverse reactions in the breed even
with this addition.

Finally, there are some vets who dismiss concerns about acepromazine and Boxers as “Internet lore.” These vets should be referred to their veterinary drug handbook entry
on acepromazine, as most if not all discuss the issues regarding Boxers and acepromazine. While a vet who has not experienced adverse effects with the drug in Boxers may be comfortable with its use, the owner is the primary patient advocate and their wishes should be respected.

With the availability of other tranquilizers and preanesthetic drugs which are as effective as acepromazine, a knowledgeable Boxer owner is completely with his/her rights to insist the drug not be used on their dog, especially in light of the continued widespread veterinary caution against the use of the drug in the Boxer breed.

A list of veterinary textbooks, reference books, and veterinary organization websites which include cautions about use of the drug in the Boxer breed:
This is a collection of references from various veterinary publications which discuss the increased sensitivity of Boxers to acepromazine. This is in no way a complete list.
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Acepromazine may cause syncope in brachycephalic breeds. Boxers are reportedly very sensitive to the hypotensive and bradycardiac effects of acepromazine and even small doses should be used cautiously in this breed.

Psychopharmacology of Animal Behavior Disorders
1998
Nicholas H. Dodman, Louis Schuster
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Giant breeds and greyhounds may be extremely sensitive to the drug, while terrier breeds are somewhat resistant to its effects. Boxers are reported to be very sensitive to the hypotensive and bradycardiac effects of acepromazine....

Veterinary Drug Handbook
Third Edition, 1999
Donald C. Plumb
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Adverse [effects]: Hypotension, penile paralysis (equine), decreased seizure threshold, prolonged duration with liver diseas; anecdotal reports of profound respiratory and cardiovascular depression in Boxers.

Veterinary Anesthesia
2000
Janyce L. Cornick-Seahorn
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Fainting and cardiovascular collapse has been reported to occur occasionally in all species of animal following the use of even low doses of acepromazine. In some cases it may have been due to administration to a hypovolaemic animal but in others it has not been explained. Some strains of Boxers are known for collapsing after a very small dose of acepromazine given by any route, and it has been suggested that this may be due to orthostatic hypotension or to vasovagal syncope.

Veterinary Anaesthesia
Tenth Edition, 2001
L.W. Hall, K.W. Clarke, C.M. Trim
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Phenothiazines such as acepromazine should be used with caution in Greyhounds and other coursing hounds and in brachycephalic breeds. In the Boxer in particular fainting may be precipitated.

The Veterinary Formulary
2001
Yolande M. Bishop, British Veterinary Association
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Acepromazine can cause syncope associated with high vagal tone and subsequent bradycardia; this occurs in brachycephalic breeds, particularly in Boxers.

Veterinary Pharmacology & Therapeutics
Eighth Edition, 2001
H. Richard Adams
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What is meant by 'boxer sensitivity to acepromazine' or 'boxer-ace syndrome'? What could be the factors influencing its occurrence?
The administration of acepromazine to some boxers can induce profound bradycardia, associated with hypotension and collapse of the animal. This is a dramatic event experienced by a generation of veterinary clinicians, especially in the United Kingdom. Some clinicians report that doses as low as 0.01 mg/kg given subcutaneously have induced collapse in an otherwise healthy animal. It appears to be related to certain strains of the breed. An explanation for this problem such as excessive vagal response or epinephrine reversal has not been documented.

Veterinary Anesthesia and Pain Management Secrets
2002
Stephen A. Greene
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Some Boxers have demonstrated pronounced side effects and have even died after administration of acepromazine as an adjuvant to opioid analgesia.

Handbook of Veterinary Pain Management
2002
James S. Gaynor, William Muir
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Fainting associated with high levels of vagal tone (sometimes termed vasovagal syncope) has been described in brachycephalic breeds, particularly boxers, given acepromazine. In these cases collapse is associated with bradycardia and treatment involves the administration of an anticholinergic druce such as atropine.

Small Animal Clinical Pharmacology
2002
Jill E. Maddison, Stephen W. Page, David Church
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Boxers are known to be unduly susceptible to ACP [acepromazine], and occasionally respond to the drug by collapsing with profound hypotension and bradycardia.

Anaesthesia for Veterinary Nurses
2003
Elizabeth Welsh
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Disadvantages:....Syncope: some breed-lines of Boxers collapse after low doses.

Veterinary Nursing
Third Edition, 2004
D.R. Lane, B. Cooper
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Boxers are prone to vasovagal syncope with acepromazine and should receive an anticholinergic if acepromazine is used. Alternatively, it should be avoided.

Veterinary Dentistry for the General Practitioner
2004
Cecilia Gorrel
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Acepromazine is safe in healthy young adult animals, but should be avoided in patients with a known seizure history, liver disease, heart disease, geriatric or pediatric patients, any dehydrated animal, and Boxers.

Shelter Medicine for Veterinarians and Staff
2004
Lila Miller, Stephen Zawistowski
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Boxers are very sensitive to the effects of acepromazine; use with caution at very low dose rates.

Clinical Procedures in Veterinary Nursing
2004
Victoria Aspinall
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Giant breeds, as well as greyhounds, appear quite sensitive to the clinical effects of the drug, yet terrier breeds appear more resistant. Conversely, boxer dogs are predisposed to the hypotensive and bradycardiac effects of the drug.

Handbook of Veterinary Drugs
Third Edition, 2004
D.G. Allen, J.K. Pringle, D.A. Smith with K. Pasloske and K. Day
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There are medical contraindications for ACP, including epilepsy, brachycephalic breeds, history of respiratory depression, hepatic dysfunction, renal compromise and hypotension.

Behaviour Problems in Small Animals
2005
John Bowen, Sarah Heath
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Acepromazine should not be used in patients with a history of seizures and should be used with caution in young or debilitated animals, geriatric patients, pregnant females, giant breeds, greyhounds, and boxers.

Veterinary Psychopharmacology
2006
Sharon L. Crowell-Davis, Thomas Murray
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The side-effects of short term use of acepromazine include the following (Booth, 1988; Dodman,1998):

Hypotension (often accompanied by a compensatory tachycardia)
Bradycardia
Syncope, particularly in brachycephalic breeds, the Boxer being especially sensitive
Hypothermia

Currently posted on the website of the South African Veterinary Council.
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In some dogs, particularly Boxers and other short-nosed breeds, spontaneous fainting or syncope may occur, due to sinoatrial block caused by excessive vagal tone, and an attack may be precipitated by acepromazine

This is a direct quote from the Novartis product insert, and is currently posted on both of these websites:
Veterinary Medicines Directorate (UK; government agency of the Department for Environment, Food and Rural Affairs). (Word document)

National Office of Animal Health (UK)

(information above courtesy of Jennifer Walker, Newcastle Boxers)

Further warning from a boxer breeder and veterinarian:

This drug is the most commonly prescribed tranquilizer in veterinary medicine. It is also used orally and is prescribed for owners who want to tranquilize their dogs for air travel. I would strongly recommend that Boxer owners avoid the use of this drug, especially when the dog will be unattended and/or unable to receive emergency medical care if it is needed.

- Wendy Wallner, DVM December, 1995

When you first take your boxer to a vet (or to a new vet), for any kind of treatment have them write in red on the outside of the patient record "NO ACE". Be firm! If they refuse to do this then I would immediately remove my dog and find another vet.
Don't be fooled by an uninformed vet...this is a matter of LIFE AND DEATH!