Chlorpromazine Hydrochloride

INDICATIONS AND USAGE 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 HCl 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 three times daily. Increase gradually until effective dose is reached – usually 400 mg daily. Outpatients – 10 mg three times daily or four times daily, or 25 mg twice daily or three times daily. More Severe Cases – 25 mg three times daily. 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 to 50 mg three times daily. Nausea and Vomiting – 10 to 25 mg every four to six hours, as needed, increased, if necessary. Presurgical Apprehension – 25 to 50 mg, 2 to 3 hours before the operation. Intractable Hiccups – 25 to 50 mg three times daily or four times daily. If symptoms persist for 2 to 3 days, parenteral therapy is indicated. Acute Intermittent Porphyria – 25 to 50 mg three times daily or four times daily. Can usually be discontinued after several weeks, but maintenance therapy may be necessary for some patients. DOSAGE AND ADMINISTRATION - 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: 1⁄4 mg/pound body weight every four to six hours, as needed (e.g., for 40-pound child – 10 mg every four to six hours). 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 severely disturbed mentally retarded patient …

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 fourth and tenth 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 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 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: Extrapyramidal Symptoms– Neuromuscular reactions include dystonias, 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 these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An …

DESCRIPTION Chlorpromazine hydrochloride, USP, a dimethylamine derivative of phenothiazine, has a chemical formula of 2-chloro-10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride. It is available in tablets for oral administration. It has the following structural formula: C 17 H 19 ClN 2 S. HCl M.W. 355.33 g/mol Chlorpromazine hydrochloride occurs as white or slightly creamy white, crystalline powder which darkens on prolonged exposure to light. Each tablet for oral administration contains 10 mg, 25 mg, 50 mg, 100 mg, or 200 mg of chlorpromazine hydrochloride, USP. Inactive ingredients: calcium sulfate dihydrate, ferric oxide red, ferric oxide yellow, ferrosoferric oxide, glyceryl monostearate, hypromellose, lactose monohydrate, magnesium stearate, medium chain triglycerides, polyethylene glycol, propylene glycol, shellac glaze, sucrose and talc. FDA approved dissolution test specifications differ from USP. spl-chlorpromazine-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 hydrochloride. 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 hydrochloride tablets, USP, 10 mg are round shaped, red colored, biconvex, sugar coated tablets, imprinted with ‘ 509 ’ on one side and no print on reverse side. Bottle of 100 with child-resistant closure NDC 63304-185-01 Bottle of 1000 with child-resistant closure NDC 63304-185-10 Chlorpromazine hydrochloride tablets, USP, 25 mg are round shaped, light yellow colored, biconvex, sugar coated tablets, imprinted with ‘ 510 ’ on one side and no print on reverse side. Bottle of 100 with child-resistant closure NDC 63304-143-01 Bottle of 1000 with child-resistant closure NDC 63304-143-10 Chlorpromazine hydrochloride tablets, USP, 50 mg are round shaped, white colored, biconvex, sugar coated tablets, imprinted with ‘ 511 ’ on one side and no print on reverse side. Bottle of 100 with child-resistant closure NDC 63304-122-01 Bottle of 1000 with child-resistant closure NDC 63304-122-10 THESE TABLET STRENGTHS LISTED BELOW ARE FOR USE ONLY IN SEVERE NEUROPSYCHIATRIC CONDITIONS. Chlorpromazine hydrochloride tablets, USP, 100 mg are round shaped, white colored, biconvex, sugar coated tablets, imprinted with ‘ 512 ’ on one side and no print on reverse side. Bottle of 100 with child-resistant closure NDC 63304-114-01 Bottle of 1000 with child-resistant closure NDC 63304-114-10 Chlorpromazine hydrochloride tablets, USP, 200 mg are round shaped, white colored, biconvex, sugar coated tablets, imprinted with ‘ 513 ’ on one side and no print on reverse side. Bottle of 100 with child-resistant closure NDC 63304-083-01 Bottle of 1000 with child-resistant closure NDC 63304-083-10 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from light and moisture. These containers are not for household use. If dispensed for outpatient use, a well closed, light-resistant, child-resistant containers should be utilized. Keep out of reach of children. To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For more information, call Sun Pharmaceutical Industries Inc. at 1-800-818-4555. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 MADE IN INDIA November 2020 FDA-03