Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.


Chemistry - Acepromazine maleate (formerly acetylpromazine) is a phenothiazine derivative whichoccurs as a yellow, odorless, bitter tasting powder. One gram is soluble in 27 ml of water, 13 ml ofalcohol, 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 physicallyincompatible with phenothiazines. However, glycopyrrolate has been demonstrated to be compatible with promazine HCl for injection.


Acepromazine is a phenothiazine neuroleptic agent. While the exact mechanismsof action are not fully understood, the phenothiazines block post-synaptic dopamine receptors in theCNS and may also inhibit the release of, and increase the turnover rate of dopamine. They arethought to depress portions of the reticular activating system which assists in the control of bodytemperature, 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 tranquilizingaction. Additional pharmacologic actions that acepromazine possess, include antiemetic, antispasmodic, and hypothermic actions. Some researchers have reported that acepromazine hasanticonvulsant activity, but in veterinary medicine it is generally felt that phenothiazines should notbe 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 effectoccurs with regard to the blood gas picture, pH or oxyhemoglobin saturation. A dose dependentdecrease 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 incentral venous pressure, a vagally induced bradycardic effect and transient sinoatrial arrest. Thebradycardia 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 thearrhythmias induced by the ultra-short acting barbiturates, and protect against the ventricularfibrillatory 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: " an aid in controlling intractable animals.....alleviate itchingas a result of skin irritation; as an antiemetic to control vomiting associated with motion sickness"and as a preanesthetic agent. In horses, " an aid in controlling fractious animals", and inconjunction 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 smalldoses to help control behavior.
Although not approved, it is used as a tranquilizer (see doses) in swine, cattle, rabbits, sheep andgoats. Acepromazine has also been shown to reduce the incidence of halothane-induced malignant hyperthermia in susceptible pigs.


The pharmacokinetics of acepromazine has been studied in the horse (Ballardet 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 IVadministration, with peak effects seen in 30-60 minutes. The elimination half-life in horsesapproximately 3 hours.
Acepromazine is metabolized in the liver with both conjugated and unconjugated metaboliteseliminated 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 anestheticsfollowing acepromazine. Cautious use and smaller doses of acepromazine should be given toanimals with hepatic dysfunction, cardiac disease, or general debilitation. Because of its hypotensiveeffects, acepromazine is relatively contraindicated in patients with hypovolemia or shock.
Phenothiazines are relatively contraindicated in patients with tetanus or strychnine intoxication dueto effects on the extrapyrimidal system.
Intravenous injections should be made slowly. Do not administer intra-arterially in horses; maycause 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 uponwhen 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 geriatricpatients, very low doses have been associated with prolonged effects of the drug. Giant breeds andgreyhounds may be extremely sensitive to the drug, while terrier breeds are somewhat resistant toits effects. Boxers are reported to very sensitive to the hypotensive and bradycardic effects ofacepromazine and should be used cautiously and in small doses in this breed. Atropine is oftensuggested 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 causeregurgitation 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 bothcentral mechanisms and also through the alpha-adrenergic actions of the drug. Cardiovascularcollapse (secondary to bradycardia and hypotension) has been described in all major species. Dogsmay be more sensitive to these effects than other animals.
In male large animals, acepromazine causes protrusion of the penis and corresponds to thesedative 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 permanentparalysis of the penis retractor muscle. Other symptoms that have been reported in horses includeexcitement, restlessness, sweating, trembling, tachypnea, tachycardia and, rarely, seizures and recumbency.
While acepromazine is a good tranquilizer, its effects of causing penis extension in horses andprolapse 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 ananimal 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 theinjection site.
Overdosage - The LD50 in mice is 61 mg/kg after IV dosage and 257 mg/kg after oral dose. Dogsreceiving 20 - 40 mg/kg over 6 weeks apparently demonstrated no adverse effects. Dogs graduallyreceiving up to 220 mg/kg orally exhibited signs of pulmonary edema and hyperemia of internalorgans, but no fatalities were noted.
Because of the apparent relative low toxicity of acepromazine, most overdoses can be handled bymonitoring the animal and treating symptoms if they occur. Massive oral overdoses shoulddefinitely be treated by emptying the gut if possible. Hypotension should not be treated withepinephrine; use either phenylephrine or norepinephrine (levarterenol). Seizures may be controlledwith 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 anorganophosphate agent as their effects may be potentiated. Other CNS depressant agents(barbiturates, narcotics, anesthetics, etc.) may cause additive CNS depression if used withacepromazine.
Quinidine when given with phenothiazines may cause additive cardiac depression.
Antidiarrheal mixtures (e.g., Kaolin/pectin, bismuth subsalicylate mixtures) and antacids maycause reduced GI absorption of oral phenothiazines. Increased blood levels of both drugs mayresult 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 bedecreased if given concurrently with phenothiazines.
Procaine activity may be enhanced by phenothiazines.