prochlorperazine
Compazine, Stemetil ◆

prochlorperazine edisylate
Compazine

prochlorperazine maleate
Compazine, Compazine Spansule, Stemetil ◆

Available forms
Available by prescription only
prochlorperazine edisylate
Injection: 5 mg/ml
Spansules (sustained-release): 10 mg, 15 mg
Suppositories: 2.5 mg, 5 mg, 25 mg
Syrup: 1 mg/ml
prochlorperazine maleate
Tablets: 5 mg, 10 mg, 25 mg

Indications and dosages
 Preoperative nausea control. Adults: 5 to 10 mg I.M. 1 to 2 hours before induction of anesthesia, repeated once in 30 minutes if needed; or 5 to 10 mg I.V. 15 to 30 minutes before induction of anesthesia, repeated once if needed; or 20 mg/L D₅W and normal saline solution by I.V. infusion, added to infusion 15 to 30 minutes before induction. Maximum parenteral dosage is 40 mg daily.
 Severe nausea, vomiting. Adults: 5 to 10 mg P.O. t.i.d. or q.i.d. Or, 15 mg of sustained-release form P.O. on arising. Or, 10 mg of sustained-release form P.O. q 12 hours. Or, 25 mg P.R. b.i.d. Or, 5 to 10 mg I.M. injected deeply into upper outer quadrant of gluteal region. Repeat q 3 to 4 hours, p.r.n. May be given I.V. Maximum parenteral dose is 40 mg daily.
Children weighing 18 to 39 kg (40 to 86 lb): 2.5 mg P.O. or P.R. t.i.d.; or 5 mg P.O. or P.R. b.i.d.; or 0.132 mg/kg deep I.M. injection. (Control usually obtained with one dose.) Maximum, 15 mg daily.
Children weighing 14 to 17 kg (31 to 37 lb): 2.5 mg P.O. or P.R. b.i.d. or t.i.d.; or 0.132 mg/kg deep I.M. injection. (Control usually is obtained with one dose.) Maximum, 10 mg daily.
Children weighing 9 to 14 kg (20 to 31 lb): 2.5 mg P.O. or P.R. daily or b.i.d.; or 0.132 mg/kg deep I.M. injection. (Control usually is obtained with one dose.) Maximum, 7.5 mg daily.
 Anxiety. Adults: 5 mg P.O. t.i.d. or q.i.d.
 Psychotic disorders. Adults: 5 to 10 mg P.O. or 10 to 20 mg I.M. t.i.d. or q.i.d.; up to 150 mg daily P.O. for hospitalized patients.

Pharmacodynamics
Antipsychotic action: Thought to exert antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects.
Antiemetic action: Effects attributed to dopamine receptor blockade in the medullary chemoreceptor trigger zone.
 Drug has many other central and peripheral effects: Produces alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated activity. Most prevalent adverse reactions are extrapyramidal. Used primarily as an antiemetic; ineffective against motion sickness.

Pharmacokinetics
Absorption: Rate and extent of absorption vary with administration route. Oral tablet absorption is erratic and variable; onset of action ranging from 1/2 to 1 hour. Oral concentrate absorption more predictable. I.M. drug absorbed rapidly.
Distribution: Distributed widely into body, including breast milk. 91% to 99% protein-bound. Peak effect at 2 to 4 hours; steady state serum levels within 4 to 7 days.
Metabolism: Metabolized extensively by liver; no active metabolites formed. Duration of action about 3 to 4 hours; 10 to 12 hours for extended-release form.
Excretion: Mostly excreted in urine via kidneys; some excreted in feces via biliary tract.

Contraindications and precautions
Contraindicated in patients hypersensitive to phenothiazines and in those with CNS depression including coma; during pediatric surgery; when using spinal or epidural anesthetic, adrenergic blockers, or ethanol; and in infants younger than age 2.
  Use cautiously in patients with impaired CV function, glaucoma, or seizure disorders; in those who have been exposed to extreme heat; and in children with acute illness.

Interactions
Drug-drug. Anticonvulsants: Decreases seizure threshold. May need to adjust anticonvulsant dose.
Antacids containing aluminum and magnesium; antidiarrheals: Inhibits absorption. Separate administration times by at least 2 hours.
Appetite suppressants, sympathomimetics (such as ephedrine [commonly found in nasal sprays], epinephrine, phenylephrine): Decreases stimulatory and pressor effects; may cause epinephrine reversal (hypotensive response to epinephrine). Use together cautiously; don’t use with epinephrine.
Atropine, other anticholinergics (such as antidepressants, antihistamines, antiparkinsonians, MAO inhibitors, meperidine, phenothiazines): Causes oversedation, paralytic ileus, visual changes, and severe constipation. Avoid use together.
Beta blockers: Increases plasma levels and toxicity of both drugs. Adjust dosage as needed.
Bromocriptine: Antagonizes prolactin secretion. Monitor patient closely.
Centrally acting antihypertensives (such as clonidine, guanabenz, guanadrel, guanethidine, methyldopa, reserpine): Inhibits blood pressure response. Monitor blood pressure.
CNS depressants (such as anesthetics [epidural, general, spinal], barbiturates, narcotics, parenteral magnesium sulfate, tranquilizers): Causes oversedation, respiratory depression, and hypotension. Monitor patient closely.
Lithium: Causes severe neurologic toxicity with encephalitis-like syndrome; decreases therapeutic response to prochlorperazine. Monitor patient closely.
Metrizamide: Increases risk of seizures. Use together cautiously.
Oral anticoagulants: Diminishes effects of anticoagulant. Monitor PT and INR.
Pimozide: Prolongs QT interval. Avoid use together.
Phenobarbital: Enhances renal excretion of prochlorperazine; decreases phenobarbital levels. Adjust dosage as needed.
Phenytoin: Inhibits metabolism and increases toxicity of phenytoin. Monitor patient closely.
Thiazide diuretics: Accentuates orthostatic hypotension. Use together cautiously.
Tricyclic antidepressants: Increases TCA serum levels. Monitor patient closely.
Drug-herb. Kava: May increase risk of dystonic reactions. Discourage use together.
Yohimbe: Phenothiazines may increase risk of toxicity. Discourage use together.
Drug-food. Caffeine: Decreases therapeutic response to prochlorperazine. Discourage use together.
Drug-lifestyle. Alcohol use: Cause additive effects. Discourage alcohol use.
Heavy smoking: Increases prochlorperazine metabolism. Discourage smoking.
Sun exposure: Causes photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: extrapyramidal reactions, sedation, pseudoparkinsonism, EEG changes, dizziness.
CV: orthostatic hypotension, tachycardia, ECG changes.
EENT: ocular changes, blurred vision.
GI: dry mouth, constipation, ileus, increased appetite.
GU: urine retention, dark urine, menstrual irregularities, inhibited ejaculation, hyperprolactinemia.
Hematologic: transient leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia.
Hepatic: cholestatic jaundice.
Metabolic: weight gain, hyperglycemia or hypoglycemia.
Skin: mild photosensitivity, allergic reactions, exfoliative dermatitis.
Other: gynecomastia.

Effects on lab test results
• May increase or decrease blood glucose level.
• May decrease WBC, granulocyte, and platelet counts. May increase or decrease liver function test values.

Overdose and treatment
Toxicity may cause CNS depression characterized by deep, unarousable sleep and possible coma, hypotension or hypertension, extrapyramidal symptoms, dystonia, abnormal involuntary muscle movements, agitation, seizures, arrhythmias, ECG changes, hypothermia or hyperthermia, and autonomic nervous system dysfunction.
 To treat, don’t induce vomiting. Drug inhibits cough reflex, and aspiration may occur. Use gastric lavage, then activated charcoal and saline cathartics; dialysis doesn’t help. Regulate body temperature as needed. Treat hypotension with I.V. fluids. Don’t give epinephrine. Treat seizures with parenteral diazepam or barbiturates; arrhythmias with parenteral phenytoin (1 mg/kg with rate titrated to blood pressure); and extrapyramidal reactions with benztropine or parenteral diphenhydramine 2 mg/ kg/minute.

Special considerations
• Liquid and injectable formulations may cause a rash after contact with skin.
• Drug may cause a pink to brown discoloration of urine.
• Drug is linked to a high risk of extrapyramidal effects and, in institutionalized psychiatric patients, photosensitivity reactions; patient should avoid exposure to sunlight or heat lamps.
• Oral formulations may cause stomach upset. Administer with food or fluid.
• Don’t give sustained-release form to children.
• Solution for injection may be slightly discolored. Don’t use if excessively discolored or if a precipitate is evident. Contact pharmacist.
• Dilute concentrate in 60 to 120 ml (2 to 4 oz) of water. Store suppository form in a cool place.
• Give I.V. dose slowly (5 mg/minute). I.M. injection may cause skin necrosis; take care to prevent extravasation. Don’t mix with other drugs in syringe. Don’t administer S.C.
• Administer I.M. injection deep into upper outer quadrant of buttock. Massaging area after administration may prevent formation of abscesses.
• Drug is ineffective in treating motion sickness.
• Protect liquid form from light.
• Prochlorperazine causes false-positive test results for urinary porphyrins, urobilinogen, amylase, and 5-hydroxyindoleacetic acid because of darkening of urine by metabolites; also causes false-positive urine pregnancy results in tests using human chorionic gonadotropin as the indicator.
Breast-feeding patients
• Drug may appear in breast milk. Use cautiously in breast-feeding women. Potential benefits to mother should outweigh potential harm to infant.
Pediatric patients
• Drug isn’t recommended for patients younger than age 2 or weighing less than 9 kg (20 lb).
Geriatric patients
• Elderly patients tend to require lower dosages, adjusted to individual effects. These patients are at greater risk for adverse reactions, especially tardive dyskinesia, other extrapyramidal effects, and hypotension.

Patient education
• Explain risks of dystonic reactions and tardive dyskinesia. Tell patient to promptly report abnormal body movements.
• Tell patient to avoid sun exposure and to wear sunscreen when going outdoors to prevent photosensitivity reactions. (Note that heat lamps and tanning beds also may cause skin burning or skin discoloration.)
• Tell patient to avoid spilling liquid form. Contact with skin may cause rash and irritation.
• Warn patient to avoid extremely hot or cold baths and exposure to temperature extremes, sunlamps, or tanning beds; drug may cause thermoregulatory changes.
• Advise patient to take drug exactly as prescribed, not to double the dose after missing one, and not to share drug with others.
• Warn patient to avoid alcohol or drugs that may cause excessive sedation.
• Tell patient to dilute concentrate in water; explain dropper technique of measuring dose; teach correct use of suppository.
• Tell patient that ice chips, sugarless hard candy or chewing gum can alleviate dry mouth.
• Urge patient to store drug safely away from children.
• Inform patient that interactions are possible with many drugs. Warn him to seek medical approval before taking OTC or herbal products.
• Warn patient not to stop taking drug suddenly and to promptly report difficulty urinating, sore throat, dizziness, or fainting. Reassure patient that most reactions can be relieved by reducing dosage.
• Caution patient to avoid hazardous activities that require alertness until drug’s effects are known. Reassure patient that sedative effects subside and become tolerable in several weeks.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use