- Required doses used may be lower than those listed on the approved label.
- Relatively long duration of action
- Negligible analgesic effects alone, but can potentiate effects of opiates
- Dose may need to be reduced in debilitated or geriatric animals, in those with hepatic or cardiac disease, or when combined with other agents.
- Certain dog breeds (eg, giant breeds, sight hounds) and dogs with the multidrug sensitivity gene (MDR1 gene, also known as ABCB1 gene) mutation may be overly sensitive to effects and require dose reduction. 1
- May cause significant hypotension1, 3
Acepromazine is FDA-approved for use in dogs, cats, and horses. Indications for dogs and cats include as an aid in controlling intractable animals and alleviating itching as a result of skin irritation, as an antiemetic to control vomiting associated with motion sickness, and as a preanesthetic agent. Acepromazine has minimal effect on respiratory function; thus, it can be a useful tranquilizer/sedative in small animals with upper airway obstruction (eg, laryngeal paralysis). Acepromazine has negligible analgesic effects; however, when combined with analgesics, acepromazine can potentiate the analgesic effect of analgesics.
Acepromazine has a depressant effect on the central nervous system, causing sedation, muscular relaxation, lowered heart rate and an overall reduction in activity. The rapid action exerts an almost immediate calming effect, with a low order of toxicity, making it one of the most commonly used tranquilizers in veterinary medicine.
Acepromazine is FDA-approved for use in dogs, cats, and horses.
As regards mechanism of action, acepromazine is a phenothiazine neuroleptic agent. Phenothiazines block postsynaptic dopamine receptors in the CNS and may inhibit the release of dopamine and increase its turnover rate. They are thought to depress portions of the reticular activating system that assist in the control of body temperature, basal metabolic rate, emesis, vasomotor tone, hormonal balance, and alertness. In addition, phenothiazines have varying degrees of anticholinergic, antihistaminic, antispasmodic, and α-adrenergic blocking effects. 1 The primary desired effect for the use of acepromazine in veterinary medicine is its tranquilizing/sedating action. Additional pharmacologic actions of acepromazine include antiemetic, antispasmodic, and hypothermic actions.
In dogs and cats, oral bioavailability is ≈20% and elimination half-lives are ≈7.1 hours (IV) and 16 hours (PO). 2 In horses, acepromazine 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 to 60 minutes.
In a study, horses appeared sedate (chin-to-ground measurement) within 5 minutes of IV administration as compared with 15 minutes for oral and sublingual administration; sedation lasted 2 hours. Elimination half-lives after oral, sublingual, and IV administration were 8.6 hours, 6.7 hours, and 5.2 hours, respectively. 1 Acepromazine is metabolized in the liver with both conjugated and unconjugated metabolites eliminated in the urine. Metabolites may be found in equine urine up to 96 hours after administration.
Contraindications / Precautions:
Acepromazine potentiates the toxicity of organophosphates,
including those found in flea collars, and of procaine hydrochloride. Thus, it
is contraindicated in patients receiving those agents. Animals may require
lower doses of general anesthetics after receiving acepromazine. Acepromazine
should be used cautiously and at smaller doses in animals that are sensitive to
acepromazine, animals with hepatic dysfunction, mild cardiac disease, dehydration,
or general debilitation.
Because of its hypotensive effects, acepromazine is relatively contraindicated in patients with significant heart disease, hypovolemia, marked dehydration, hypotension, or shock. Acepromazine has been said to decrease platelet aggregation, and its use should be avoided in patients with liver disease, coagulopathies or thrombocytopenia.
The literature suggests that IV injections should be made slowly. Acepromazine should not be administered intra-arterially in horses, as it may cause severe CNS excitement/depression, seizures, and death. 1 Because of its effects on thermoregulation, acepromazine should be used cautiously in very young or debilitated animals.
When using in horses, be advised that acepromazine’s vasodilation effects may be deleterious in horses with acute colic, cantharidin toxicosis, dehydration/hypovolemia, or hypotension/shock. In a study of normal healthy horses, IV infusion of norepinephrine at 1 μg/kg/min reversed the hypotensive effects of 0.1 mg/kg acepromazine IV. 4
In dogs, the effects of acepromazine may be individually variable and breed dependent. Dogs with MDR1 gene mutation (eg, collies, Australian shepherd dogs) may develop a more pronounced sedation that persists longer than normal. 1 Acepromazine should be used very cautiously as a restraining agent in aggressive dogs, as it may make the animal more prone to startle and react to noises or other sensory inputs. 2
The effect of acepromazine on blood pressure (hypotension) is well described and should be considered during treatment planning. 1 It is believed that dogs may be more sensitive to these effects than other animals. Acepromazine has also been shown to decrease tear production in cats and rabbits.
Occasionally, an animal may develop the contradictory clinical signs of aggressiveness and generalized CNS stimulation after receiving acepromazine. IM administration may cause transient pain at the injection site. 1
In horses, temporary paralysis of the retractor penis muscle has been noted with the use of this class of tranquilizers. This risk should be considered prior to the administration of acepromazine to male horses. 3 Other side effects reported in horses include excitement, restlessness, sweating, trembling, tachypnea, tachycardia, and, rarely, seizures and recumbency. 1
The following drug interactions with acepromazine or other phenothiazines have either been reported or are theoretical in humans or animals and may be of significance in veterinary patients. 1 Unless otherwise noted, use together is not necessarily contraindicated, but the potential risks should be weighed and additional monitoring performed when appropriate.
- ACETAMINOPHEN: Possible increased risk for hypothermia when used concurrently with a dose of acepromazine.
- ANTACIDS: Concurrent use may cause reduced GI absorption of oral phenothiazines.
- ANTIDIARRHEAL MIXTURES (eg, kaolin/pectin, bismuth subsalicylate mixtures): Concurrent use may reduce GI absorption of oral phenothiazines.
- BARBITURATES (eg, phenobarbital, pentobarbital): May cause additive CNS depression if used with acepromazine
- CISAPRIDE: Concurrent use with phenothiazines may increase risk for QT interval prolongation, cardiac arrhythmias, torsade de pointes, and death. Combination is contraindicated.
- DOPAMINE: Acepromazine may impair the vasopressive action of dopamine.
- EMETICS: Acepromazine may reduce the effectiveness of emetics.
- EPINEPHRINE: Contraindicated in the treatment of acute hypotension produced by phenothiazine-derivative tranquilizers, as further depression of blood pressure can occur
- FLUOXETINE: May increase levels of chlorpromazine due to inhibition of CYP2D6; this interaction may apply to acepromazine.
- HYPOTENSIVE AGENTS: Concurrent use may increase risk for hypotension and orthostasis.
- METOCLOPRAMIDE: Concurrent use may increase risk for extrapyramidal adverse effects.
- METRONIDAZOLE: Concurrent use may increase risk for QT interval prolongation, cardiac arrhythmias, and torsade de pointes. Should be used cautiously and the patient monitored for development of adverse effects.
- ONDANSETRON: Concurrent use of ondansetron may increase risk for QT interval prolongation, cardiac arrhythmias, and torsade de pointes.
- OPIATES (eg, fentanyl, hydromorphone, morphine): May enhance the hypotensive effects of acepromazine; doses of acepromazine are generally reduced when used with an opiate.
- ORGANOPHOSPHATE AGENTS: Acepromazine should not be given within one month of worming or accidental exposure to these agents, as their effects may be potentiated.
- PHENYTOIN: Metabolism may be decreased if given concurrently with phenothiazines.
- PROCAINE: Activity may be enhanced by phenothiazines. Concurrent use with acepromazine is contraindicated.
- PROPRANOLOL: Increased blood levels of both drugs may result if administered concurrently.
- QUINIDINE: Concurrent use with phenothiazines may cause additive cardiac depression. 1
In humans, the FDA categorizes phenothiazines as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats; or these drugs are safe if they are not administered when the animal is near term). 1
Dogs: As an aid in tranquilization, controlling intractable animals, and alleviating itching as a result of skin irritation; as an antiemetic to control vomiting associated with motion sickness; and as a preanesthetic agent (FDA approved; labeled dose): 0.55 – 2.2 mg/kg PO (dose may be repeated as required) or 0.55 – 1.1 mg/kg IV, IM, or SC
Cats: As an aid in controlling intractable animals and alleviating itching as a result of skin irritation, as an antiemetic to control vomiting associated with motion sickness, and as a preanesthetic agent (FDA approved; labeled dose): 1.1 – 2.2 mg/kg (cats) IV, IM, or SC
Dogs and cats
1. Injectable: 0.01 – 0.2 mg/kg IV (slowly), IM, or SC once. Total dose should not exceed more than 3 mg in dogs (1 mg in cats). Doses as low as 0.02 – 0.03 mg/kg may be sufficient.
a) Anesthetic premedication (extra-label): 0.03 – 0.125 mg/kg IM, SC, or slow IV. (NOTE: Many consider this dose too high; 0.02 – 0.05 mg/kg is more reasonable). Following acepromazine administration, anesthetic induction agent doses can often be reduced by approximately ⅓.
b) Tranquilization/sedation: 0.0625 – 0.125 mg/kg IM, SC, or slow IV. Lower doses should be used for tranquilization and higher doses used for sedation. Maximum dose is 4 mg per animal. Typically, single doses are administered; long-term use is not recommended. In cats, 0.05 – 0.1 mg/kg IM or IV in combination with an opioid has been suggested.
2. Oral: Anecdotal dose recommendations vary widely but generally are similar to the labeled dose range of 0.55 – 2.2 mg/kg PO, although some think that doses at the higher end of this range are too high. If oral doses require repeating, they are usually given every 6 to 12 hours. 1
As an aid in controlling fractious animals and in conjunction with local anesthesia for various procedures and treatments (FDA-approved; labeled dosage), recommended dosages of acepromazine are: 0.044 – 0.088 mg/kg (2 – 4 mg/100 lb body weight) IV (slowly), IM, or SC.
1. Sedation, tranquilization, premedication, vasodilator (for laminitis); When used alone, acepromazine is usually dosed similarly to the label: 0.02 – 0.1 mg/kg IM, IV, or SC. When used in combination with drugs such as butorphanol as a premedication or to increase blood flow in the treatment of laminitis, recommended doses are usually on the low end of this range.
2. Anesthetic premedication, to facilitate restraint, or as an aid in travel: Preanesthetic: 0.02 – 0.05 mg/kg IM or slow IV; sedation/restraint: 0.05 – 0.1 mg/kg IM or slow IV. Administer up to 15 minutes prior to the desired effect and await clinical signs of tranquilization before travel or subsequent administration of anesthetic. For tranquilization, adjust dose to maintain desired effect for the duration of travel or procedure.
Sedation in donkeys: 0.1 mg/kg IV produced sedation ≈10 minutes after administration, which lasted ≈80 minutes. 1
1Plumb's Veterinary Drugs.
2Hashem A, Kietzmann M, Scherkl R. Pharmacokinetics and bioavailability of acepromazine in plasma of the dog. Dtsch Tierarztl Wochenschr. 1992;99(10):396-398.
4Pequito M, Amory H, de Moffarts B, Busoni V, Serteyn D, Sandersen C. Evaluation of acepromazine-induced hemodynamic alterations and reversal with norepinephrine infusion in standing horses. Can Vet J. 2013;54(2):150-156.