PROCHLORPERAZINE

Chemistry - Prochlorperazine, a piperazine phenothiazine derivative, is available commercially asthe base in rectal formulations, the edisylate salt in injectable and oral solutions, and as the maleatesalt in oral tablets and capsules. Each 8 mg of the maleate salt and 7.5 mg of the edisylate salt areapproximately equivalent to 5 mg of prochlorperazine base.
The base occurs as a clear, to pale yellow, viscous liquid that is very slightly soluble in water andfreely soluble in alcohol. The edisylate salt occurs as white to very light yellow, odorless, crystallinepowder. 500 mg are soluble in 1 ml of water and 750 ml of alcohol. The maleate salt occurs as awhite or pale yellow, practically odorless, crystalline powder. It is practically insoluble in water oralcohol.
The commercial injection is a solution of the edisylate salt in sterile water. It has a pH of 4.2-6.2.

Storage, Stability, Compatibility

Store in tight, light resistant containers at room temperature.
Avoid temperatures above 40°C and below freezing. A slight yellowing of the oral or injectablesolution has no effects on potency or efficacy, but do not use if a precipitate forms or the solution issubstantially discolored.
The following products have been reported to be compatible when mixed with prochlorperazineedisylate injection: all usual IV fluids, ascorbic acid injection, atropine sulfate, butorphanol tartrate, chlorpromazine HCl, dexamethasone sodium phosphate, droperidol, fentanyl citrate, glycopyrrolate, hydroxyzine HCl, lidocaine HCl, meperidine HCl, metoclopramide, morphine sulfate, nafcillinsodium, nalbuphine HCl, pentazocine lactate, perphenazine, promazine HCl, promethazine, scopolamine HBr, sodium bicarbonate, and vitamin B complex with C.
The following drugs have been reported to be incompatible when mixed with prochlorperazineedisylate: aminophylline, amphotericin B, ampicillin sodium, calcium gluceptate, choramphenicolsodium succinate, chlorothiazide sodium, dimenhydrinate, hydrocortisone sodium succinate, methohexital sodium, penicillin G sodium, phenobarbital sodium, pentobarbital sodium, andthiopental sodium. Do not mix with other drugs/diluents having parabens as preservatives.
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 - PROCHLORPERAZINE

The basic pharmacology of prochlorperazine is similar to that of the other phenothiazines (refer to the acepromazine monograph for more information). Prochlorperazine hasweak anticholinergic effects, strong extrapyrimidal effects, and moderate sedative effects. It hasstrong antiemetic effects and this action is used for its primary indications in both human andveterinary medicine.
Uses, Indications - The only approved products for animals are combination products containingprochlorperazine, isopropamide, with or without neomycin (Darbazine®, Neo-Darbazine®, ¯
SKB Labs). The approved indications for these products include: vomiting, non-specific gastroenteritis, drug induced diarrhea, infectious diarrhea, spastic colitis, and motion sickness in dogsand cats (injectable product only). Prochlorperazine as a single agent is used in dogs and cats as anantiemetic.

Pharmacokinetics - PROCHLORPERAZINE

Little information is available regarding the pharmacokinetics of prochlorperazine in animals, although it probably follows the general patterns of other phenothiazine agentsin absorption, distribution and elimination.
Contraindications/Precautions - The manufacturer lists glaucoma, pyloric obstruction or stenosis, and prostatic hypertrophy as contraindications for the combination product Darbazine®. Forother precautions and contraindications refer to the acepromazine monograph.

Adverse Effects, Warnings

In addition to the adverse effects listed for dogs and cats in theacepromazine monograph, Darbazine® may cause a dry mouth, dilated pupils, constipation andurinary retention secondary to the anticholinergic ingredient. Alone, prochlorperazine is most likelyto casue sedation or hypotension.
Overdosage - Refer to the information listed in the acepromazine monograph. Acute extrapyrimadal symptoms (torticollis, tremor, salivation) have been successfully treated with injectablediphenhydramine in humans.

Drug Interactions

Drug interactions for prochlorperazine include: Phenothiazines shouldnot be given within one month of worming with an organophosphate agent as their effects maybe potentiated.
Other CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) may cause additive
CNS depression if used with prochlorperazine.
Quinidine given with phenothiazines may cause additive cardiac depression. Antidiarrhealmixtures (e.g., Kaolin/pectin, bismuth subsalicylate mixtures) and antacids may cause reduced GIabsorption of oral phenothiazines. Increased blood levels of both drugs may result if propranololis administered with phenothiazines. Phenothiazines block alpha-adrenergic receptors, ifepinephrine is given, unopposed beta-activity causing vasodilation and increased cardiac rate canoccur.
Phenytoin metabolism may be decreased if given concurrently with phenothiazines.
Drug Interactions for Isopropamide (ingredient in Darbazine®): The following drugs mayenhance the activity of isopropamide and its derivatives: antihistamines, procainamide, quinidine, meperidine, benzodiazepines, phenothiazines.
The following drugs may potentiate the adverse effects of isopropamide and its derivatives:primidone, disopyramide, nitrates, long-term corticosteroid use (may increase intraocularpressure).
Isopropamide and its derivatives may enhance the actions of nitrofurantoin, thiazide diuretics, sympathomimetics.
Isopropamide and its derivatives may antagonize the actions of metoclopramide.
Drug/Laboratory Interactions - Isopropamide iodide may alter thyroid function tests (due to theiodine component) and will suppress iodine131 uptake. It is recommended that the drug bediscontinued one week prior to testing or treatment.