Medications: Thorazine^® – chlorpromazine

Chlorpromazine is indicated for:

• For the management of manifestations of psychotic disorders.
• For the treatment of schizophrenia.
• To control nausea and vomiting.
• For relief of restlessness and apprehension before surgery.
• For acute intermittent porphyria.
• As an adjunct in the treatment of tetanus.
• To control the manifestations of the manic type of manic-depressive illness.
• For relief of intractable hiccups.
• For the treatment of severe behavioral problems in children (1 to 12 years of age) marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations), and in the short-term treatment of hyperactive children who show excessive motor activity with accompanying conduct disorders consisting of some or all of the following symptoms: impulsivity, difficulty sustaining attention, aggressivity, mood lability and poor frustration tolerance.

DOSAGE AND ADMINISTRATION

ADULTS

Adjust dosage to individual and the severity of his condition, recognizing that the milligram for milligram potency relationship among all dosage forms has not been precisely established clinically. It is important to increase dosage until symptoms are controlled. Dosage should be increased more gradually in debilitated or emaciated patients. In continued therapy, gradually reduce dosage to the lowest effective maintenance level, after symptoms have been controlled for a reasonable period.

The 100 mg and 200 mg tablets are for use in severe neuropsychiatric conditions.

Elderly Patients – In general, dosages in the lower range are sufficient for most elderly patients. Since they appear to be more susceptible to hypotension and neuromuscular reactions, such patients should be observed closely. Dosage should be tailored to the individual, response carefully monitored, and dosage adjusted accordingly. Dosage should be increased more gradually in elderly patients.

Psychotic Disorders – Increase dosage gradually until symptoms are controlled. Maximum improvement may not be seen for weeks or even months. Continue optimum dosage for 2 weeks; then gradually reduce dosage to the lowest effective maintenance level. Daily dosage of 200 mg is not unusual. Some patients require higher dosages (e.g., 800 mg daily is not uncommon in discharged mental patients).

Hospitalized Patients:

Acute Schizophrenic or Manic States – It is recommended that initial treatment be with chlorpromazine hydrochloride injection until patient is controlled. Usually patient becomes quiet and co-operative within 24 to 48 hours and oral doses may be substituted and increased until the patient is calm. 500 mg a day is generally sufficient. While gradual increases to 2,000 mg a day or more may be necessary, there is usually little therapeutic gain to be achieved by exceeding 1,000 mg a day for extended periods. In general, dosage levels should be lower in the elderly, the emaciated and the debilitated.

Less Acutely Disturbed – 25 mg t.i.d. Increase gradually until effective dose is reached – usually 400 mg daily.

Outpatients – 10 mg t.i.d. or q.i.d., or 25 mg b.i.d. or t.i.d.

More Severe Cases – 25 mg t.i.d. After 1 or 2 days, daily dosage may be increased by 20 to 50 mg at semi-weekly intervals until patient becomes calm and cooperative.

Prompt Control of Severe Symptoms – Initial treatment should be with intramuscular chlorpromazine. Subsequent doses should be oral, 25 mg to 50 mg t.i.d.

Nausea and Vomiting– 10 mg to 25 mg q4 to 6h, p.r.n., increased, if necessary.

Presurgical Apprehension– 25 mg to 50 mg, 2 to 3 hours before the operation.

Intractable Hiccups– 25 mg to 50 mg t.i.d. or q.i.d. If symptoms persist for 2 to 3 days, parenteral therapy is indicated.

Acute Intermittent Porphyria– 25 mg to 50 mg t.i.d. or q.i.d. Can usually be discontinued after several weeks, but maintenance therapy may be necessary for some patients.

PEDIATRIC PATIENTS (6 months to 12 years of age)

Chlorpromazine should generally not be used in pediatric patients under 6 months of age except where potentially lifesaving. It should not be used in conditions for which specific pediatric dosages have not been established.

Severe Behavioral Problems:

Outpatients – Select route of administration according to severity of patient’s condition and increase dosage gradually as required. Oral: ¼ mg/lb body weight q4 to 6h, p.r.n. (e.g., for 40 lb child – 10 mg q4 to 6h).

Hospitalized Patients – As with outpatients, start with low doses and increase dosage gradually. In severe behavior disorders higher dosages (50 mg to 100 mg daily and in older children, 200 mg daily or more) may be necessary. There is little evidence that behavior improvement in severely disturbed mentally retarded patients is further enhanced by doses beyond 500 mg per day.

Nausea and Vomiting– Dosage and frequency of administration should be adjusted according to the severity of the symptoms and response of the patient. The duration of activity following intramuscular administration may last up to 12 hours. Subsequent doses may be given by the same route if necessary. Oral: ¼ mg/lb body weight (e.g., 40 lb child – 10 mg q4 to 6h).

Presurgical Apprehension–¼ mg/lb body weight orally 2 to 3 hours before operation.

Note: Some adverse effects of chlorpromazine may be more likely to occur, or occur with greater intensity, in patients with special medical problems, e.g., patients with mitral insufficiency or pheochromocytoma have experienced severe hypotension following recommended doses. Drowsiness, usually mild to moderate, may occur, particularly during the first or second week, after which it generally disappears. If troublesome, dosage may be lowered.

• Jaundice: Overall incidence has been low, regardless of indication or dosage. Most investigators conclude it is a sensitivity reaction. Most cases occur between the second and fourth weeks of therapy. The clinical picture resembles infectious hepatitis, with laboratory features of obstructive jaundice, rather than those of parenchymal damage. It is usually promptly reversible on withdrawal of the medication; however, chronic jaundice has been reported. If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment. Liver function tests in jaundice induced by the drug may mimic extrahepatic obstruction; withhold exploratory laparotomy until extrahepatic obstruction is confirmed.
• Hematological Disorders: including agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, aplastic anemia, thrombocytopenic purpura and pancytopenia have been reported.
• Cardiovascular
  • Postural hypotension, simple tachycardia, momentary fainting and dizziness may occur rarely, after the first oral dose. Usually recovery is spontaneous, and symptoms disappear within ½ to 2 hours. Occasionally, these effects may be more severe and prolonged, producing a shock-like condition.
  • EKG CHANGES: Particularly nonspecific, usually reversible Q and T wave distortions–have been observed in some patients receiving phenothiazine tranquilizers, including chlorpromazine. Note: Sudden death, apparently due to cardiac arrest, has been reported.
• CNS Reactions: Neuromuscular reactions include dystonia, motor restlessness, pseudo-parkinsonism and tardive dyskinesia, and appear to be dose-related. They are discussed in the following paragraphs:
  • Dystonia: Class effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. An elevated risk of acute dystonia is observed in males and younger age groups.
  • Motor Restlessness: Symptoms may include agitation or jitteriness and sometimes insomnia. These symptoms often disappear spontaneously. At times these symptoms may be similar to the original neurotic or psychotic symptoms. Dosage should not be increased until these side effects have subsided.
  • Pseudo-parkinsonism: Symptoms may include: mask-like facies, drooling, tremors, pillrolling motion, cogwheel rigidity and shuffling gait. In most cases, these symptoms are readily controlled when an anti-parkinsonism agent is administered concomitantly. Anti-parkinsonism agents should be used only when required. Generally, therapy of a few weeks to 2 or 3 months will suffice. After this time, patients should be evaluated to determine their need for continued treatment. (Note: Levodopa has not been found effective in antipsychotic-induced pseudo-parkinsonism.) Occasionally it is necessary to lower the dosage of chlorpromazine or to discontinue the drug.
  • Tardive Dyskinesia: As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The syndrome can also develop, although much less frequently, after relatively brief treatment periods at low doses. This syndrome appears in all age groups. Although its prevalence appears to be highest among elderly patients, especially elderly women, it is impossible to rely upon prevalence estimates to predict at the inception of antipsychotic treatment which patients are likely to develop the syndrome. The symptoms are persistent and, in some patients, appear to be irreversible. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities. In rare instances, these involuntary movements of the extremities are the only manifestations of tardive dyskinesia. A variant of tardive dyskinesia, tardive dystonia, has also been described.
  • Adverse Behavioral Effects – Psychotic symptoms and catatonic-like states have been reported rarely.
• OTHER CNS EFFECTS: Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. (See WARNINGS.) Cerebral edema has been reported. Convulsive seizures (petit mal and grand mal) have been reported, particularly in patients with EEG abnormalities or history of such disorders. Abnormality of the cerebrospinal fluid proteins has also been reported.
• Allergic Reactions of a mild urticarial type or photosensitivity are seen. Avoid undue exposure to sun. More severe reactions, including exfoliative dermatitis and toxic epidermal necrolysis (TEN), have been reported occasionally. Contact dermatitis has been reported in nursing personnel; accordingly, the use of rubber gloves when administering chlorpromazine liquid or injectable is recommended.
• In addition, asthma, laryngeal edema, angioneurotic edema and anaphylactoid reactions have been reported.
• Endocrine Disorders: Lactation and moderate breast engorgement may occur in females on large doses. If persistent, lower dosage or withdraw drug. False-positive pregnancy tests have been reported but are less likely to occur when a serum test is used. Amenorrhea and gynecomastia have also been reported. Hyperglycemia, hypoglycemia and glycosuria have been reported.
• Autonomic Reactions: Occasional dry mouth; nasal congestion; nausea; obstipation; constipation; adynamic ileus; urinary retention; priapism; miosis and mydriasis; atonic colon; ejaculatory disorders/impotence.
• Special Considerations in Long-Term Therapy: Skin pigmentation and ocular changes have occurred in some patients taking substantial doses of chlorpromazine for prolonged periods.
• Other Adverse Reactions: Mild fever may occur after large IM doses. Hyperpyrexia has been reported. Increases in appetite and weight sometimes occur. Peripheral edema and a systemic lupus erythematosus-like syndrome have been reported.
• Note: There have been occasional reports of sudden death in patients receiving phenothiazines. In some cases, the cause appeared to be cardiac arrest or asphyxia due to failure of the cough reflex.

Do not use in patients with known hypersensitivity to phenothiazines.

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.).

WARNINGS AND PRECAUTIONS:

• Increased Mortality in Elderly Patients with Dementia-Related Psychosis
• The use of chlorpromazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye’s syndrome.
• Chlorpromazine Hydrochloride Injection contains sodium metabisulfite and sodium sulfite, sulfites that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.
• Tardive Dyskinesia
• Neuroleptic Malignant Syndrome (NMS)
• An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) has occurred in a few patients treated with lithium plus an antipsychotic. In some instances, the syndrome was followed by irreversible brain damage.
• Patients with bone marrow depression or who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a phenothiazine should not receive any phenothiazine, including chlorpromazine, unless in the judgment of the physician the potential benefits of treatment outweigh the possible hazard.
• Chlorpromazine may impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, caution patients about activities requiring alertness (e.g., operating vehicles or machinery).
• The use of alcohol with this drug should be avoided due to possible additive effects and hypotension.
• Chlorpromazine may counteract the antihypertensive effect of guanethidine and related compounds.
• Falls: Chlorpromazine may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.
• Safety for the use of chlorpromazine during pregnancy has not been established.
• Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.
• There is evidence that chlorpromazine is excreted in the breast milk of nursing mothers.
• Leukopenia, Neutropenia and Agranulocytosis: In clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents.
• Chlorpromazine should be administered cautiously to persons with cardiovascular, liver or renal disease. There is evidence that patients with a history of hepatic encephalopathy due to cirrhosis have increased sensitivity to the CNS effects of chlorpromazine (i.e., impaired cerebration and abnormal slowing of the EEG).
• Because of its CNS depressant effect, chlorpromazine should be used with caution in patients with chronic respiratory disorders such as severe asthma, emphysema and acute respiratory infections, particularly in children (1 to 12 years of age).
• Because chlorpromazine can suppress the cough reflex, aspiration of vomitus is possible.
• Chlorpromazine prolongs and intensifies the action of CNS depressants such as anesthetics, barbiturates and narcotics. When chlorpromazine is administered concomitantly, about 1/4 to 1/2 the usual dosage of such agents is required.
• When chlorpromazine is not being administered to reduce requirements of CNS depressants, it is best to stop such depressants before starting chlorpromazine treatment. These agents may subsequently be reinstated at low doses and increased as needed.
• Note: Chlorpromazine does not intensify the anticonvulsant action of barbiturates. Therefore, dosage of anticonvulsants, including barbiturates, should not be reduced if chlorpromazine is started. Instead, start chlorpromazine at low doses and increase as needed.
• Use with caution in persons who will be exposed to extreme heat, organophosphorus insecticides and in persons receiving atropine or related drugs.
• Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Although disturbances such as galactorrhea, amenorrhea, gynecomastia and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs.
• Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents treated with certain antipsychotics.
• As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, chlorpromazine should be used with caution in patients with glaucoma.
• Chlorpromazine diminishes the effect of oral anticoagulants.
• Phenothiazines can produce alpha-adrenergic blockade.
• Chlorpromazine may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that chlorpromazine may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.
• Concomitant administration with propranolol results in increased plasma levels of both drugs.
• Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines.
• The presence of phenothiazines may produce false-positive phenylketonuria (PKU) test results.
• Drugs which lower the seizure threshold, including phenothiazine derivatives, should not be used with metrizamide.
• As with other phenothiazine derivatives, chlorpromazine should be discontinued at least

48 hours before myelography, should not be resumed for at least 24 hours post procedure, and should not be used for the control of nausea and vomiting occurring either prior to myelography or post procedure with metrizamide.

• Long-Term Therapy: To lessen the likelihood of adverse reactions related to cumulative drug effect, patients with a history of long-term therapy with chlorpromazine and/or other antipsychotics should be evaluated periodically to decide whether the maintenance dosage could be lowered, or drug therapy discontinued.
• Antiemetic Effect: The antiemetic action of chlorpromazine may mask the signs and symptoms of overdosage of other drugs and may obscure the diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor and Reye’s syndrome. (See WARNINGS.) When chlorpromazine is used with cancer chemotherapeutic drugs, vomiting as a sign of the toxicity of these agents may be obscured by the antiemetic effects of chlorpromazine.
• Abrupt Withdrawal: Like other phenothiazines, chlorpromazine is not known to cause psychic dependence and does not produce tolerance or addiction. There may be, however, following abrupt withdrawal of high-dose therapy, some symptoms resembling those of physical dependence such as gastritis, nausea and vomiting, dizziness and tremulousness. These symptoms can usually be avoided or reduced by gradual reduction of the dosage or by continuing concomitant anti-parkinsonism agents for several weeks after chlorpromazine is withdrawn.

Not stated

Symptoms: Primarily symptoms of central nervous system depression to the point of somnolence or coma. Hypotension and extrapyramidal symptoms. Other possible manifestations include agitation and restlessness, convulsions, fever, autonomic reactions such as dry mouth and ileus, EKG changes and cardiac arrhythmias.

Treatment: It is important to determine other medications taken by the patient since multiple drug therapy is common in overdosage situations. Treatment is essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage. Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus. Extrapyramidal symptoms may be treated with anti-parkinsonism drugs, barbiturates or diphenhydramine. See prescribing information for these products. Care should be taken to avoid increasing respiratory depression.

If administration of a stimulant is desirable, amphetamine, dextroamphetamine or caffeine with sodium benzoate is recommended. Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided.

If hypotension occurs, the standard measures for managing circulatory shock should be initiated. If it is desirable to administer a vasoconstrictor, norepinephrine and phenylephrine are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause a further lowering of blood pressure. Limited experience indicates that phenothiazines are not dialyzable.