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Acepromazine Maleate *

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

Chemistry - Acepromazine maleate (formerly acetylpromazine ) is a phenothiazine derivative which occurs as a yellow, odorless, bitter tasting powder. One gram is soluble in 27 ml of water, 13 ml of alcohol, and 3 ml of chloroform. Acepromazine is also known as “ACE” , ACP , Plegicil® , Notensil® , & Atravet®.

 

Storage/Stability/Compatibility - Store protected from light. Tablets should be stored in tight containers. Acepromazine injection should be kept from freezing.

 

Although controlled studies have not documented the compatibility of these combinations, acepromazine has been mixed with atropine, buprenorphine, chloral hydrate, ketamine, meperidine, oxymorphone, and xylazine. Both glycopyrrolate and diazepam have been reported to be physically incompatible with phenothiazines. However, glycopyrrolate has been demonstrated to be compatible with promazine HCl for injection.

 

Pharmacology - Acepromazine is a phenothiazine neuroleptic agent. While the exact mechanisms of action are not fully understood, the phenothiazines block postsynaptic dopamine receptors in the CNS and may also inhibit the release of, and increase the turnover rate of dopamine. They are thought to depress portions of the reticular activating system which assists in the control of body temperature, basal metabolic rate, emesis, vasomotor tone, hormonal balance, and alertness. Additionally, phenothiazines have varying degrees of anticholinergic, antihistaminic, antispasmodic, and alpha-adrenergic blocking effects.

 

The primary desired effect for the use of acepromazine in veterinary medicine is its tranquilizing action. Additional pharmacologic actions that acepromazine possess, include antiemetic, antispasmodic, and hypothermic actions. Some researchers have reported that acepromazine has anticonvulsant activity, but in veterinary medicine it is generally felt that phenothiazines should not be used in epileptic animals or those susceptible to seizures (e.g., post-myelography) as it may precipitate seizures.

 

Acepromazine may decrease respiratory rates, but studies have demonstrated that little or no effect occurs with regard to the blood gas picture, pH or oxyhemoglobin saturation. A dose dependent decrease in hematocrit is seen within 30 minutes after dosing in the horse and the dog. In horses, hematocrit values may decrease up to 50% of pre-dose values which is probably due to increased splenic sequestration of red cells.

 

Besides a lowering of arterial blood pressure in the dog, acepromazine causes an increase in central venous pressure, a vagally induced bradycardic effect and transient sinoatrial arrest. The bradycardia may be negated by a reflex tachycardic effect secondary to decreases in blood pressure. Acepromazine also has antidysrhythmic effects. Acepromazine has been demonstrated to inhibit the arrhythmias induced by the ultra-short acting barbiturates, and protect against the ventricular fibrillatory actions of halothane and epinephrine. Other pharmacologic actions are discussed in the adverse effects section below.

 

Uses/Indications - Acepromazine is approved for use in dogs, cats, and horses. Approved indications for dogs and cats include: “...as an aid in controlling intractable animals.....alleviate itching as a result of skin irritation; as an antiemetic to control vomiting associated with motion sickness” and as a preanesthetic agent. In horses, “...as an aid in controlling fractious animals”, and in conjunction with local anesthesia for various procedures and treatments (Package Insert - PromAce®, Fort Dodge). It is also commonly used in horses as a pre-anesthetic agent, at very small doses to help control behavior.

 

Although not approved, it is used as a tranquilizer (see doses) in swine, cattle, rabbits, sheep and goats. Acepromazine has also been shown to reduce the incidence of halothane-induced malignant hyperthermia in susceptible pigs.

 

Pharmacokinetics - The pharmacokinetics of acepromazine has been studied in the horse (Ballard et al. 1982). The drug has a fairly high volume of distribution (6.6 L/kg), and is more than 99% protein bound. The onset of action is fairly slow, requiring up to 15 minutes following IV administration, with peak effects seen in 30-60 minutes. The elimination half-life in horses approximately 3 hours.

 

Acepromazine is metabolized in the liver with both conjugated and unconjugated metabolites eliminated in the urine. Metabolites may be found in equine urine for up to 96 hours after dosing. Do not administer to racing animals within 4 days of racing.

 

Contraindications/Precautions - Animals may require lower dosages of general anesthetics following acepromazine. Cautious use and smaller doses of acepromazine should be given to animals with hepatic dysfunction, cardiac disease, or general debilitation. Because of its hypotensive effects, acepromazine is relatively contraindicated in patients with hypovolemia or shock. Phenothiazines are relatively contraindicated in patients with tetanus or strychnine intoxication due to effects on the extrapyrimidal system.

 

Intravenous injections should be made slowly. Do not administer intra-arterially in horses; may cause severe CNS excitement/depression, seizures and death. Because of its effects on thermoregulation, use cautiously in very young or debilitated animals.

 

Acepromazine has no analgesic effects; treat animals with appropriate analgesics to control pain. The tranquilization effects of acepromazine can be overridden and it cannot always be counted upon when used as a restraining agent. Do not administer to racing animals within 4 days of a race.

 

In dogs, acepromazine’s effects may be individually variable and breed dependent. In geriatric patients, very low doses have been associated with prolonged effects of the drug. Giant breeds and greyhounds may be extremely sensitive to the drug, while terrier breeds are somewhat resistant to its effects. Boxers are reported to very sensitive to the hypotensive and bradycardic effects of acepromazine and should be used cautiously and in small doses in this breed. Atropine is often suggested to be given with acepromazine to help negate its bradycardic effects.

 

In addition to the legal aspects (not approved) of using acepromazine in cattle, the drug may cause regurgitation of ruminal contents when inducing general anesthesia.

 

Adverse Effects/Warnings - Acepromazine’s effect on blood pressure (hypotension) is well described and an important consideration in therapy. This effect is thought to be mediated by both central mechanisms and also through the alpha-adrenergic actions of the drug. Cardiovascular collapse (secondary to bradycardia and hypotension) has been described in all major species. Dogs may be more sensitive to these effects than other animals.

 

In male large animals, acepromazine causes protrusion of the penis and corresponds to the sedative effects of the drug. In horses, this effect may last 2 hours. Stallions should be given acepromazine with caution as injury to the penis can occur with resultant swelling and permanent paralysis of the penis retractor muscle. Other symptoms that have been reported in horses include excitement, restlessness, sweating, trembling, tachypnea, tachycardia and, rarely, seizures and recumbency.

 

While acepromazine is a good tranquilizer, its effects of causing penis extension in horses and prolapse of the membrana nictitans in horses and dogs, may make its use unsuitable for show an­imals. There are also ethical considerations regarding the use of tranquilizers prior to showing an animal or having the animal examined before sale.

 

Occasionally an animal may develop the contradictory symptoms of aggressiveness and generalized CNS stimulation after receiving acepromazine. IM injections may cause transient pain at the injection site.

 

Overdosage - The LD50 in mice is 61 mg/kg after IV dosage and 257 mg/kg after oral dose. Dogs receiving 20 - 40 mg/kg over 6 weeks apparently demonstrated no adverse effects. Dogs gradually receiving up to 220 mg/kg orally exhibited signs of pulmonary edema and hyperemia of internal organs, but no fatalities were noted.

 

Because of the apparent relative low toxicity of acepromazine, most overdoses can be handled by monitoring the animal and treating symptoms if they occur. Massive oral overdoses should definitely be treated by emptying the gut if possible. Hypotension should not be treated with epinephrine; use either phenylephrine or norepinephrine (levarterenol). Seizures may be controlled with barbiturates or diazepam. Doxapram has been suggested as an antagonist to the CNS depressant effects of acepromazine.

 

Drug Interactions - Acepromazine should not be given within one month of worming with an organophosphate agent as their effects may be potentiated. Other CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) may cause additive CNS depression if used with acepromazine. Quinidine when given with phenothiazines may cause additive cardiac depression. Antidiarrheal mixtures (e.g., Kaolin/pectin, bismuth subsalicylate mixtures) and antacids may cause reduced GI absorption of oral phenothiazines. Increased blood levels of both drugs may result if propranolol is administered with phenothiazines.  Phenothiazines block alpha-adrenergic receptors and if epinephrine is given, can lead to unopposed beta-activity causing vasodilation and increased cardiac rate. Phenytoin metabolism may be decreased if given concurrently with phenothiazines. Procaine activity may be enhanced by phenothiazines.

 

Doses - Note: The manufacturer’s dose of 0.5 - 2.2 mg/kg for dogs and cats is considered by many clinicians to be 10 times greater than is necessary for most indications. Give IV doses slowly; allow at least 15 minutes for onset of action.

Horses:

a)   0.04 - 0.1 mg/kg IV or IM (Robinson 1987)

b)   0.044 - 0.088 mg/kg (2 - 4 mg/100 lbs. body weight) IV, IM or SQ (Package Insert, PromAce® - Fort Dodge)

c)  0.02 - 0.05 mg/kg IM or IV as a preanesthetic (Booth 1988a)

d)  Neuroleptanalgesia:0.02 mg/kg given with buprenorphine (0.004 mg/kg IV) or xy­

lazine (0.6 mg/kg IV) (Thurmon and Benson 1987)

 

Elephants:

 

CAUTION!  Sedative and anesthetic drug dosages for African elephants often vary from those for Asian elephants.  Do not assume that the recommendations for one species can be applied to the other.  Significant variation may also occur between individual elephants.  The information provided here should be used as a guideline only.  Consultation with experienced colleagues is advised. 

 

Refer to the etorphine monograph for information on the use of acepromazine in combination with etorphine (Immobilon®).

 

a) Adverse effect reported: Photosensitization (appears first as a triangle on the dorsal aspect of the neck) has occurred in Asian elephants receiving given (60-80 mg) and xylazine (100 mg/metric ton) and in one 5 ton elephant that was given a total of 90 mg of acepromazine and 300 mg of xylazine and then transported in an open truck (Cheeran, 2002).

 

b) 40-60 mg acepromazine/metric ton (0.04-0.06 mg/kg) combined with 100 mg xylazine/metric ton for Asian elephants (Cheeran, et.al. 2002).

 

c) 0.1 mg/kg IM for Asian elephants; if combined with other drugs, dose can be reduced by up to 50% (Nayar, 2002).

 

d) 50-60 mg/ton IM for Asian elephants; do not expose to direct sunlight for long periods (Cheeran,1995).

 

e) For sedation of African or Asian elephants: 0.004-0.005 mg/kg (total dose 10-30 mg)  (Fowler, 1995).

 

f) For sedation, the following are total doses by age category (no species differences are specified): Adults: 30 mg; juvenile–adult: 10-20 mg; baby-juvenile: 5-10 mg (Kock, et.al. 1993).  (Author’s (Mikota) note:  The animal category and drug dose column headings for acepromazine are misaligned in this reference and may cause confusion. The doses listed here are correctly matched to their respective age categories).

 

g) Recumbent immobilization was induced in 12-15 minutes using 150 mg acepromazine combined with 350 mg xylazine IM in two Asian cows weighing 2500 and 3000 kg.  Duration of effect was 60 minutes and was sufficient for resection and extraction of bullets in one case and resection and removal of glass from the foot in the other (Nayar, et.al. 1992).

 

h) In elephants, the dose will depend upon the state of the animal and the level of tranquilization needed.  Dosages in the range of 0.007 to 0.07 mg/kg IM will provide adequate sedation in elephants that are not excited.  The lower dose dosage will calm, the higher dosage will result in heavy sedation (Schmidt, 1986).

 

i) 0.03-0.07 mg/kg (Fowler, 1981).

 

Elephant References:

 

a) Cheeran,J. 2002.  Adverse drug experiences in elephants.  Journal of Indian Veterinary Association Kerala 7:(3):61

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

c) Nayar,K.N.M., Chandrasekharan,K., and Radhakrishnan,K. 2002. Management of surgical affections in captive elephants. Journal of Indian Veterinary Association Kerala 7:(3):55-59

d) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants . In: Daniel,J.C. (Editor), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India pp. 430-438

e)Fowler,M.E., 1995. Elephants.  In: Restraint and handling of wild and domestic animals.  Iowa State University Press, Ames, Iowa, USA pp. 265-269

f) Kock,R.A., Morkel,P., and Kock,M.D., 1993. Current immobilization procedures used in elephants. In: Fowler,M.E. (Editor), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA pp. 436-441

g) Nayar,K.N.M., Radhakrishnan,K., Chandrasekharan,K., Cheeran,J.V., Ravindran,S., and George,P.O., 1992. Anaesthesia for surgical manipulations in the elephant. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 156-158

h) Schmidt,M.J., 1986. Proboscidea (Elephants). In: Fowler,M.E. (Editor), Zoo and wild animal medicine. W.B. Saunders, Philadelphia,PA, USA pp. 884-923

i) Fowler,M.E. 1981. Problems with immobilizing and anesthetizing elephants. Proceedings of the American Association of Zoo Veterinarians 87-91

Monitoring Parameters -

1)   Cardiac rate/rhythm/blood pressure if indicated and possible to measure

2)   Degree of tranquilization

3)   Male horses should be checked to make sure penis retracts and is not injured.

4)   Body temperature (especially if ambient temperature is very hot or cold)

 

Client Information/FDA Approval Status - May discolor the urine to a pink or red-brown color; this is not abnormal.

Acepromazine is approved for use in dogs, cats, and horses not intended for food.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times -

 

Veterinary-Approved Products:

Acepromazine Maleate for Injection 10 mg/ml for injection in 50 ml vials;PromAce® (Fort Dodge); generic; (Rx). Approved for use in dogs, cats and horses not intended for food.

 

Acepromazine Maleate Tablets 5, 10, & 25 mg in bottles of 100 and 500 tablets; PromAce ® (Fort Dodge); generic; (Rx). Approved for use in dogs, cats and horses not intended for food.

 

Human-Approved Products: None

 

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