Chlorpromazine Hydrochloride

INDICATIONS AND USAGE 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 hyper excitable 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. Increase parenteral dosage only if hypotension has not occurred. Before using IM, see Important Notes On Injection. 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 Intramuscular: 25 mg (1 mL). If necessary, give additional 25 to 50 mg injection in 1 hour. Increase subsequent IM doses gradually over several days–up to 400 mg q4-6h in exceptionally severe cases–until patient is controlled. Usually the patient becomes quiet and cooperative within 24 to 48 hours and oral doses may be substituted. Prompt Control of Severe Symptoms Intramuscular: 25 mg (1 mL). If necessary, repeat in 1 hour. Subsequent doses should be oral, 25-50 mg tid. NAUSEA AND VOMITING Intramuscular: 25 mg (1 mL). If no hypotension occurs, give 25 to 50 mg q3-4h prn, until vomiting stops. Then switch to oral dosage. During Surgery Intramuscular: 12.5 mg (0.5 mL). Repeat in 1/2 hour if necessary and if no hypotension occurs. IV: 2 mg per fractional injection, at 2-minute intervals. Do not exceed 25 mg. Dilute to 1 mg/mL, i.e., 1 mL (25 mgmixed with 24 mL of saline. PRESURGICAL APPREHENSION Intramuscular: 12.5 to 25 mg (0.5-1 mL), 1 to 2 hours before operation. INTRACTABLE HICCUPS If symptoms persist for 2 to 3 days after trial with oral therapy, give 25 to 50 mg (1 to 2 mL) Intramuscular. Should symptoms persist, use slow intravenous infusion with patient flat in bed: 25 to 50 mg (1 to 2 mL) in 500 to 1000 mL of saline. Follow blood pressure closely. ACUTE INTERMITTENT PORPHYRIA Intramuscular: 25 mg (1 mL) tid or qid until patient can take oral therapy. TETANUS Intramuscular: 25 to 50 mg (1-2 mL) given 3 or 4 times daily, usually in conjunction with barbiturates. Total doses and frequency of administration must be determined by the patient’s response, starting with low doses and increasing gradually. Intravenous: 25 to 50 mg (1 to 2 mL). Dilute to at least 1 mg per mL and administer at a rate of 1 mg per minute. 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. Intramuscular: 1/4 mg/lb body weight q6-8h, prn. Hospitalized Patients As with outpatients, start with low doses and increase dosage gradually. In severe behavior disorders, higher dosages (50 to 100 mg daily, and in older children, 200 mg daily or more) may be necessary. There is little evidence that behavior improvement in seve…

WARNINGS Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Chlorpromazine Hydrochloride Injection, USP is not approved for the treatment of patients with dementia-related psychosis ( see BOXED WARNING ). The extrapyramidal symptoms which can occur secondary to chlorpromazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye’s syndrome or other encephalopathy. 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. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, 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. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, antipsychotics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome. For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS and ADVERSE REACTIONS . Neuroleptic Malignant Syndrome (NMS) A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). The diagnostic evaluati…

CONTRAINDICATIONS 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.).

ADVERSE REACTIONS 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. There is no conclusive evidence that preexisting liver disease makes patients more susceptible to jaundice. Alcoholics with cirrhosis have been successfully treated with chlorpromazine without complications. Nevertheless, the medication should be used cautiously in patients with liver disease. Patients who have experienced jaundice with a phenothiazine should not, if possible, be reexposed to chlorpromazine or other phenothiazines. 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. AGRANULOCYTOSIS Warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate cellular depression, stop treatment and start antibiotic and other suitable therapy. Most cases have occurred between the 4th and 10th weeks of therapy; patients should be watched closely during that period. Moderate suppression of white blood cells is not an indication for stopping treatment unless accompanied by the symptoms described above. Cardiovascular HYPOTENSIVE EFFECTS Postural hypotension, simple tachycardia, momentary fainting and dizziness may occur after the first injection; occasionally after subsequent injections; rarely, after the first oral dose. Usually recovery is spontaneous and symptoms disappear within 1/2 to 2 hours. Occasionally, these effects may be more severe and prolonged, producing a shock-like condition. To minimize hypotension after injection, keep patient lying down and observe for at least 1/2 hour. To control hypotension, place patient in head-low position with legs raised. If a vasoconstrictor is required, norepinephrine and phenylephrine are the most suitable. Other pressor agents, including epinephrine, should not be used as they may cause a paradoxical further lowering of blood pressure. 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 (EXTRAPYRAMIDAL) 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. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While thes…