CHLORPROMAZINE HCI

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 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 & 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 DOSAGE & ADMINISTRATION- 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 IM: 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 IM: 25 mg (1 mL). If necessary, repeat in 1 hour. Subsequent doses should be oral, 25-50 mg tid. NAUSEA AND VOMITING IM: 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 IM: 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 mg) mixed with 24 mL of saline. PRESURGICAL APPREHENSION IM: 12.5 to 25 mg (0.5-1 mL), 1 to 2 hours before operation. INTRACTABLE HICCUPS If symptoms persist for 2-3 days after trial with oral therapy, give 25 to 50 mg (1-2 mL) IM. Should symptoms persist, use slow IV infusion with patient flat in bed: 25 to 50 mg (1-2 mL) in 500 to 1000 mL of saline. Follow blood pressure closely. ACUTE INTERMITTENT PORPHYRIA IM: 25 mg (1 mL) tid or qid until patient can take oral therapy. TETANUS IM: 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. IV: 25 to 50 mg (1-2 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. IM: 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 (50-100 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. Maximum IM Do …

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 the …

DESCRIPTION Chlorpromazine HCl is chemically designated as 2-Chloro-10-[3-(dimethylamino)propyl]-phenothiazine monohydrochloride and has the following structural formula: C 17 H 19 ClN 2 S • HCl MW 355.33 Chlorpromazine Hydrochloride Injection, USP is a sterile aqueous solution intended for deep intramuscular use. Each mL contains chlorpromazine hydrochloride 25 mg, ascorbic acid 2 mg, sodium metabisulfite 1 mg, sodium sulfite 1 mg and sodium chloride 6 mg in Water for Injection. pH is 3.4 to 5.4. STRUCTURE

OVERDOSAGE (See also ADVERSE REACTIONS .) 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.

HOW SUPPLIED CHLORPROMAZINE HCI INJECTION, USP is supplied in the following dosage forms. NDC 51662-1406-1 CHLORPROMAZINE HCI INJECTION, USP 50 mg/2 mL (25 mg/mL) 2 mL AMPUL HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms Chlorpromazine Hydrochloride Injection, USP 25 mg/mL is available in the following packages: 1 mL ampul packaged in 25s (NDC 0641-1397-35) 2 mL ampul packaged in 25s (NDC 0641-1398-35) Storage Protect from light, or discoloration may occur. Slight yellowing will not alter potency. Discard if markedly discolored. Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from freezing. To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Product Inquiry call 1-877-845-0689. Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mό, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL Distributed by: WEST-WARD A HIKMA COMPANY Eatontown, NJ 07724 USA Revised November 2016 462-637-02 PIN295-WES/3