chlorpromazine hydrochloride
Chlorpromanyl-20 ◆, Largactil ◆, Novo-Chlorpromazine ◆, Thorazine

Available forms
Available by prescription only
Capsules (sustained-release): 30 mg, 75 mg, 150 mg
Injection: 25 mg/ml
Oral concentrate: 30 mg/ml, 100 mg/ml
Suppositories: 25 mg, 100 mg
Syrup: 10 mg/5 ml
Tablets: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg

Indications and dosages
 Psychotic disorders. Hospitalized adults: For acutely disturbed or manic patients, 25 mg I.M. If needed, give an additional 25 to 50 mg I.M. in 1 hour. Increase subsequent I.M. doses gradually over several days up to 400 mg I.M. q 4 to 6 hours. May substitute P.O. dose when able; 500 mg P.O. daily up to 1,000 mg is usually sufficient, but may go as high as 2,000 mg daily. For less acutely disturbed patients, 25 mg P.O. t.i.d. Increase until effective dose is reached (usually 400 mg daily).
Outpatient adults: 10 mg P.O. t.i.d. or q.i.d. or 25 mg b.i.d. or t.i.d. In more severe cases, 25 mg P.O. t.i.d. After 1 to 2 days, dose may be increased 20 to 50 mg daily at semi-weekly intervals.
Children age 6 months and older: 0.5 mg/kg P.O. q 4 to 6 hours; or I.M. q 6 to 8 hours; or 1 mg/kg P.R. q 6 to 8 hours. Maximum I.M. dose is 40 mg in children younger than age 5 or weighing less than 22.7 kg (50 lb), and 75 mg in children ages 5 to 12 or weighing 22.7 to 45.5 kg (50 to 100 lb).
 Nausea, vomiting. Adults: 10 to 25 mg P.O. q 4 to 6 hours, p.r.n.; or 50 to 100 mg P.R. q 6 to 8 hours, p.r.n.; or 25 mg I.M. initially. If no hypotension occurs, 25 to 50 mg I.M. q 3 to 4 hours may be given, p.r.n., until vomiting stops.
Children age 6 months and older: 0.55 mg/kg P.O. q 4 to 6 hours, p.r.n.; or I.M. q 6 to 8 hours, p.r.n.; or 1.1 mg/kg P.R. q 6 to 8 hours, p.r.n. Maximum I.M. dose in children younger than age 5 or weighing less than 22.7 kg (50 lb) is 40 mg. Maximum I.M. dose in children ages 5 to 12 or weighing 22.7 to 45.5 kg (50 to 100 lb) is 75 mg.
 Intractable hiccups, acute intermittent porphyria. Adults: 25 to 50 mg P.O. or I.M. t.i.d. or q.i.d. For hiccups, if symptoms persist, 25 to 50 mg diluted in 500 to 1,000 ml of normal saline solution and infuse I.V. slowly with patient in supine position.
 Tetanus. Adults: 25 mg to 50 mg I.M. or I.V. t.i.d. or q.i.d.
Children age 6 months and older: 0.5 mg/kg I.M. or I.V. q 6 to 8 hours. Maximum parenteral dose in children weighing less than 23 kg (50 lb) is 40 mg daily; for children weighing 23 to 45 kg (50 to 100 lb), maximum parenteral dose is 75 mg daily, except in severe cases.
 Surgery. Adults: Preoperatively, 25 to 50 mg P.O. 2 to 3 hours before surgery or 12.5 to 25 mg I.M. 1 to 2 hours before surgery; during surgery, 12.5 mg I.M., repeated in 30 minutes, if needed, or fractional 2-mg doses I.V. at 2-minute intervals up to maximum of 25 mg; postoperatively, 10 to 25 mg P.O. q 4 to 6 hours or 12.5 to 25 mg I.M., repeated in 1 hour, if needed.
Children age 6 months and older: Preoperatively, 0.5 mg/kg P.O. 2 to 3 hours before surgery or I.M. 1 to 2 hours before surgery; during surgery, 0.25 mg/kg I.M., repeated in 30 minutes, if needed, or fractional 1-mg doses I.V. at 2-minute intervals, up to maximum of 0.25 mg/kg; postoperatively, 0.55 mg/kg P.O. or I.M., oral dose repeated q 4 to 6 hours or I.M. dose repeated in 1 hour, if needed, and if hypotension doesn’t occur.
≡ Dosage adjustment. Dose may need to be decreased in elderly, debilitated, or emaciated patients.

Pharmacodynamics
Antipsychotic and antiemetic actions: Drug is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thereby inhibiting dopamine-mediated effects; antiemetic effects are attributed to dopamine receptor blockade in the medullary chemoreceptor trigger zone. Drug has many other central and peripheral effects; it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated activity. Its most prominent adverse reactions are antimuscarinic and sedative.

Pharmacokinetics
Absorption: Rate and extent of absorption vary with route of administration. Oral tablet absorption is erratic; sustained-release preparations have similar absorption. Oral concentrates and syrups are much more predictable; I.M. drug is absorbed rapidly.
Distribution: Distributed widely into the body, including breast milk; level is usually higher in CNS than in plasma. Steady-state serum level is achieved within 4 to 7 days. Drug is 91% to 99% protein-bound.
Metabolism: Metabolized extensively by the liver and forms 10 to 12 metabolites; some are pharmacologically active.
Excretion: Mostly excreted as metabolites in urine; some is excreted in feces via the biliary tract. It may undergo enterohepatic circulation.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in patients with CNS depression, bone marrow suppression, subcortical damage, or coma.
  Use cautiously in acutely ill or dehydrated children; geriatric or debilitated patients; and in patients with impaired renal or hepatic function, severe CV disease, glaucoma, prostatic hyperplasia, respiratory or seizure disorders, hypocalcemia, reaction to insulin or electroconvulsive therapy, or exposure to heat, cold, or organophosphate insecticides.

Interactions
Drug-drug. Antiarrhythmics, disopyramide, procainamide, quinidine: Increases risk of arrhythmias and conduction defects. Avoid use together.
Anticholinergics: Increases anticholinergic activity and aggravates parkinsonian symptoms. Use cautiously.
Beta blockers: May inhibit chlorpromazine metabolism, increasing plasma levels and toxicity. Monitor patient closely.
Centrally acting antihypertensives: May decrease blood pressure. Monitor patient closely.
CNS depressants, parenteral magnesium sulfate: Additive effects are likely. Avoid use together.
Epinephrine: May cause epinephrine reversal. Avoid use together.
Lithium: May cause severe neurologic toxicity and decreased response to chlorpromazine. Avoid use together.
Propylthiouracil: Increases risk of agranulocytosis. Avoid use together.
Sympathomimetics: May decrease stimulatory and pressor effects. Avoid use together.
Warfarin: Decreases anticoagulant effect. Monitor INR and PT.
Drug-food. Caffeine: Causes pharmacokinetic alterations and decreased therapeutic response. Tell patient to avoid caffeinated foods and beverages.
Drug-lifestyle. Alcohol use: Additive effects are likely. Discourage alcohol use.
Heavy smoking: May reduce response to chlorpromazine. Discourage smoking.
Sun exposure: Photosensitivity reactions may occur. Advise patient to take precautions.

Adverse reactions
CNS: extrapyramidal reactions, drowsiness, sedation, seizures, tardive dyskinesia, pseudoparkinsonism, dizziness, neuroleptic malignant syndrome.
CV: orthostatic hypotension, tachycardia, ECG changes.
EENT: ocular changes, blurred vision, nasal congestion.
GI: dry mouth, constipation, nausea.
GU: urine retention, menstrual irregularities, inhibited ejaculation, priapism.
Hematologic: leukopenia, agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia, thrombocytopenia.
Hepatic: jaundice.
Skin: mild photosensitivity, allergic reactions, pain at I.M. injection site, sterile abscess, skin pigmentation.
Other: gynecomastia.
After abrupt withdrawal of long-term therapy: gastritis, nausea, vomiting, dizziness, tremor.

Effects on lab test results
• May increase liver function test values and eosinophil count. May decrease hemoglobin and WBC, granulocyte, and platelet counts.

Overdose and treatment
CNS depression is characterized by deep, unarousable sleep and possible coma, hypotension, or hypertension, extrapyramidal symptoms, abnormal involuntary muscle movements, agitation, seizures, arrhythmias, ECG changes, hypothermia or hyperthermia, and autonomic nervous system dysfunction.
 Treatment is symptomatic and supportive and includes maintaining vital signs, airway, stable body temperature, and fluid and electrolyte balance.
 Don’t induce vomiting: Drug inhibits cough reflex, and aspiration may occur. Use gastric lavage, then activated charcoal and saline solution 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 adjusted to blood pressure); extrapyramidal reactions with benztropine 1 to 2 mg or parenteral diphenhydramine 10 to 50 mg.

Special considerations
 ALERT I.V. form should be used only during surgery or for severe hiccups. Dilute injection to 1 mg/ml with normal saline solution and administer at 1 mg/2 minutes for children and 1 mg/ minute for adults.
• Store suppository form in a cool place.
• Give I.M. injection deep in the upper outer quadrant of the buttocks. Injection is usually painful; massaging the area after administration may prevent abscess formation.
• If tissue irritation occurs, chlorpromazine injection may be diluted with normal saline solution or 2% procaine.
• Liquid and injectable forms may cause a rash if skin contact occurs.
• Solution for injection may be slightly discolored. Don’t use if drug is excessively discolored or if a precipitate is evident. Monitor patient’s blood pressure before and after parenteral administration.
• Evaluate patient for signs and symptoms of tardive dyskinesia.
• Monitor CBC in patients receiving prolonged therapy.
• Monitor patient for cholestatic jaundice (upper abdominal pain, nausea, yellow skin, flulike symptoms, rash, fever, eosinophilia, bile in the urine, elevated serum bilirubin, alkaline phosphatase and transaminase levels). Weekly urine bilirubin tests during the first month of treatment may detect cholestatic jaundice.
• Drug causes false-positive test results for urinary porphyrins, urobilinogen, amylase, and 5- hydroxyindoleacetic acid because of darkening of urine by metabolites; it also causes false-positive results in urine pregnancy tests using human chorionic gonadotropin.
Breast-feeding patients
• Drug appears in breast milk. Potential benefits to the woman should outweigh potential harm to the infant.
Pediatric patients
• Drug isn’t recommended for patients younger than age 6 months. Sudden infant death syndrome has been reported in children younger than age 1 receiving drug. Extrapyramidal effects may be more common in children.
Geriatric patients
• Older patients tend to require lower doses, adjusted individually. Adverse reactions, especially tardive dyskinesia and other extrapyramidal effects, are more likely to develop in elderly patients.

Patient education
• Explain risks of dystonic reactions and tardive dyskinesia, and tell patient to report involuntary body movements or painful muscle contractions.
• Warn patient to avoid extremely hot or cold baths and temperature extremes, sunlamps, and tanning beds. Drug may cause thermoregulatory changes.
• Tell patient not to spill the liquid preparation on the skin because rash and irritation may result.
• Explain that sustained-release preparations shouldn’t be crushed or opened, but swallowed whole.
• Tell patient to dilute concentrate in 2 to 4 oz (60 to 120 ml) of liquid, preferably water, carbonated drinks, fruit juice, tomato juice, milk, pudding, or applesauce.
• Tell patient that oral formulations may cause stomach upset and may be taken with food or fluid.
• Instruct patient to take drug exactly as prescribed and not to double dose to compensate for missed ones.
• Explain that many drug interactions are possible. Patient should seek medical approval before taking other medications.
• Tell patient not to stop taking drug suddenly.
• Encourage patient to report difficulty urinating, sore throat, dizziness, fever, or fainting.
• Advise patient to avoid hazardous activities that require alertness until the effect of the drug is established. Excessive sedative effects tend to subside after several weeks.
• Explain what fluids are appropriate for diluting the concentrate and the dropper technique for measuring dose. Teach patient how to use suppository form.
• Inform patient that sugarless chewing gum or hard candy, ice chips, or artificial saliva may alleviate dry mouth.

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