Chemistry - A propylamino phenothiazine derivative, chlorpromazine is the prototypic phenothiazine agent. It occurs as a white to slightly creamy white, odorless, bitter tasting, crystalline powder. One gram is soluble in 1 ml of water and 1.5 ml of alcohol. The commercially available injection is a solution of chlorpromazine HCl in sterile water at a pH of 3-5.
Storage/Stability/Compatibility - Protect from light and store at room temperature; avoid freezing the oral solution and injection. Dispense oral solution in amber bottles. Store oral tablets in tight containers. Do not store in plastic syringes or IV bags for prolonged periods of time as the drug may adsorb to plastic.
Chlorpromazine will darken upon prolonged exposure to light; do not use solutions that are darkly colored or if precipitates have formed. A slight yellowish color will not affect potency or efficacy. Alkaline solutions will cause the drug to oxidize.
The following products have been reported to be compatible when mixed with chlorpromazine HCl injection: all usual intravenous fluids, ascorbic acid, atropine sulfate, butorphanol tartrate, diphenhydramine, droperidol, fentanyl citrate, glycopyrrolate, heparin sodium, hydromorphone HCl, hydroxyzine HCl, lidocaine HCl, meperidine, metoclopramide, metaraminol bitartrate, morphine sulfate, pentazocine lactate, promazine HCl, promethazine, scopolamine HBr, & tetracycline HCl.
The following products have been reported as being incompatible when mixed with chlorpromazine: aminophylline, amphotericin B, chloramphenicol sodium succinate, chlorothiazide sodium, dimenhydrinate, methicillin sodium, methohexital sodium, nafcillin sodium, penicillin g potassium, pentobarbital sodium, phenobarbital sodium, and thiopental sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology - Once the principle phenothiazine used in veterinary medicine, chlorpromazine has been largely supplanted by acepromazine. It has similar pharmacologic activities as acepromazine, but is less potent and has a longer duration of action. For further information refer to the acepromazine monograph.
Uses/Indications - The clinical use of chlorpromazine as a neuroleptic agent has diminished, but the drug is still used for its antiemetic effects in small animals and occasionally as a preoperative medication and tranquilizer. As an antiemetic, chlorpromazine will inhibit apomorphine-induced emesis in the dog but not the cat. It will also inhibit the emetic effects of morphine in the dog. It does not inhibit emesis caused by copper sulfate, or digitalis glycosides.
Pharmacokinetics - Chlorpromazine is absorbed rapidly after oral administration, but undergoes extensive first pass metabolism in the liver. The drug is also well absorbed after IM injection, but onsets of action are slower than after IV administration.
Chlorpromazine is distributed throughout the body and brain concentrations are higher than those in the plasma. Approximately 95% of chlorpromazine in plasma is bound to plasma proteins (primarily albumin).
The drug is extensively metabolized principally in the liver and kidneys, but little specific information is available regarding its excretion in dogs and cats.
Contraindications/Precautions - Chlorpromazine causes severe muscle discomfort and swelling when injected IM into rabbits; use IV only in this species. See other contraindications/precautions in the acepromazine monograph found earlier in this section.
Adverse Effects/Warnings - In addition to the possible effects listed in the acepromazine monograph, chlorpromazine may cause extrapyrimidal symptoms in the cat when used at high dosages. These symptoms can include tremors, shivering, rigidity & loss of the righting reflexes. Lethargy, diarrhea, and loss of anal sphincter tone may also be seen.
Horses may develop an ataxic reaction with resultant excitation and violent consequences. These ataxic periods may cycle with periods of sedation. Because of this effect, chlorpromazine is rarely used in equine medicine today.
Overdosage - Refer to the information listed in the acepromazine monograph.
Drug Interactions - Phenothiazines should not be given within one month of worming with an organophosphate agent as their effects may be potentiated. Physostigmine toxicity may be enhanced by chlorpromazine. Toxicity of the herbicide paraquat is increased by chlorpromazine. Other CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) may cause additive CNS depression if used with phenothiazines. Quinidine given with phenothiazines can 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, if epinephrine is then given, unopposed beta-activity causing vasodilation and increased cardiac rate can occur. Phenytoin metabolism may be decreased if given concurrently with phenothiazines. Procaine activity may be enhanced by phenothiazines. Dipyrone used with chlorpromazine has been reported to cause serious hypothermia.
Horses: Note: Because of side effects (ataxia, panic reaction) this drug is not recommended for use in horses; use acepromazine or promazine if phenothiazine therapy is desired.
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. Higher doses may be needed in wild or excited animals. Unless otherwise specified, doses refer to captive elephants. The information provided here should be used as a guideline only. Consultation with experienced colleagues is advised.
a) 2000 mg orally BID was given to an adult Asian bull elephant. See text below (Cheeran, 1992).
a) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1992. A case of ochlophobia in a tusker. 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 p. 176 Full text: An adult captive tusker to be used for ceremonial purpose could not tolerate crowd (ochlophobia - fear of the crowd). The animal was put on 2000 mg of chlorpromazine twice daily orally and behaved normally during the entire festival season of 6 months. The animal again showed symptoms of fear of the crowd when the owner withdrew the drug. So the animal was put on 100 mg haloperidol twice daily orally. This relieved the symptoms very well but without sedation compared to chlorpromazine hydrochloride.
Monitoring Parameters -
1) Cardiac rate/rhythm/blood pressure if indicated and possible to measure
2) Degree of tranquilization/anti-emetic activity if indicated
3) Body temperature (especially if ambient temperature is very hot or cold)
Client Information - Avoid getting solutions on hands or clothing as contact dermatitis may develop. May discolor the urine to a pink or red-brown color; this is not abnormal.
Dosage Forms/Preparations -
Veterinary-Approved Products: None
Chlorpromazine Tablets 10 mg, 25 mg, 50 mg, 100 mg, 200 mg; Thorazine® (SKF); Generic; (Rx)
Chlorpromazine Extended-release Capsules 30 mg, 75 mg, 150 mg, 200 mg, 300 mg; Thorazine® Spansule®(SKF); (Rx)
Chlorpromazine Oral Solutions: 2 mg/ml (syrup) in 120 ml bottles; 30 mg/ml (concentrate) in 120 ml bottles, gallons; 100 mg/ml (concentrate) in 60 and 240 ml bottlesThorazine® (SKF) ; Generic; (Rx)
Rectal suppositories 25 mg, 100 mg (as base); Thorazine® (SKF); (Rx)
Injection 25 mg/ml in 1 & 2 ml amps and cartridges and 10 ml vials; Thorazine® (SKF);Ormazine® (Hauck); Generic; (Rx)
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