Chlorpromazine Information
Chlorpromazine (Chlorpromazine) Description
Chlorpromazine (Chlorpromazine) hydrochloride, 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:
Chlorpromazine (Chlorpromazine) hydrochloride occurs as white or slightly creamy white, odorless, crystalline powder which darkens on prolonged exposure to light.
Each tablet, for oral administration, contains 10, 25, 50, 100, or 200 mg Chlorpromazine (Chlorpromazine) hydrochloride. Inactive ingredients: D & C Red #30 Aluminum Lake, D & C Yellow #10 Aluminum Lake, FD & C Blue #2 Aluminum Lake, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose (monohydrate), magnesium stearate, polyethylene glycol, povidone, sodium lauryl sulfate, starch (corn), and titanium dioxide.
Chlorpromazine (Chlorpromazine) Clinical Pharmacology
The precise mechanism whereby the therapeutic effects of Chlorpromazine (Chlorpromazine) are produced is not known. The principal pharmacological actions are psychotropic. It also exerts sedative and antiemetic activity. Chlorpromazine (Chlorpromazine) has actions at all levels of the central nervous system – primarily at subcortical levels – as well as on multiple organ systems. Chlorpromazine (Chlorpromazine) has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.
Chlorpromazine (Chlorpromazine) 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.
Chlorpromazine (Chlorpromazine) 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.).
Chlorpromazine (Chlorpromazine) Warnings
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Chlorpromazine (Chlorpromazine) hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see ).
The extrapyramidal symptoms which can occur secondary to Chlorpromazine (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 (Chlorpromazine) and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye's syndrome.
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 therapy 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 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 and .
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 evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
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. Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS).
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 (Chlorpromazine) , unless in the judgment of the physician, the potential benefits of treatment outweigh the possible hazard.
Chlorpromazine (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 (Chlorpromazine) may counteract the antihypertensive effect of guanethidine and related compounds.
Safety for the use of Chlorpromazine (Chlorpromazine) during pregnancy has not been established. Therefore, it is not recommended that the drug be given to pregnant patients except when, in the judgment of the physician, it is essential. The potential benefits should clearly outweigh possible hazards. There are reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose mothers received phenothiazines.
Reproductive studies in rodents have demonstrated potential for embryotoxicity, increased neonatal mortality and nursing transfer of the drug. Tests in the offspring of the drug-treated rodents demonstrate decreased performance. The possibility of permanent neurological damage cannot be excluded.
Chlorpromazine (Chlorpromazine) Precautions
In clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents.
Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Chlorpromazine (Chlorpromazine) hydrochloride tablets USP at the first sign of a decline in WBC in the absence of other causative factors.
Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count
Given the likelihood that some patients exposed chronically to antipsychotics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.
Chlorpromazine (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 (Chlorpromazine) (i.e., impaired cerebration and abnormal slowing of the EEG).
Because of its CNS depressant effect, Chlorpromazine (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 (Chlorpromazine) can suppress the cough reflex, aspiration of vomitus is possible.
Chlorpromazine (Chlorpromazine) prolongs and intensifies the action of CNS depressants such as anesthetics, barbiturates and narcotics. When Chlorpromazine (Chlorpromazine) is administered concomitantly, about 1/4 to 1/2 the usual dosage of such agents is required. When Chlorpromazine (Chlorpromazine) is not being administered to reduce requirements of CNS depressants, it is best to stop such depressants before starting Chlorpromazine (Chlorpromazine) treatment. These agents may subsequently be reinstated at low doses and increased 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. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent a factor of potential importance if the prescribing of these drugs is contemplated in a patient with a previously detected breast cancer. 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. Neither clinical nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents treated with certain neuroleptics.
As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, Chlorpromazine (Chlorpromazine) should be used with caution in patients with glaucoma.
Chlorpromazine (Chlorpromazine) diminishes the effect of oral anticoagulants.
Phenothiazines can produce alpha-adrenergic blockade.
Chlorpromazine (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 (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 (Chlorpromazine) should be discontinued at least 48 hours before myelography, should not be resumed for at least 24 hours postprocedure, and should not be used for the control of nausea and vomiting occurring either prior to myelography or postprocedure with metrizamide.
The antiemetic action of Chlorpromazine (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 .)
When Chlorpromazine (Chlorpromazine) is used with cancer chemotherapeutic drugs, vomiting as a sign of the toxicity of these agents may be obscured by the antiemetic effect of Chlorpromazine (Chlorpromazine) .
Chlorpromazine (Chlorpromazine) Adverse Reactions
Note:
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 (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 (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.
Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. (See .)
Cerebral edema has been reported.
Convulsive seizures ( and ) have been reported, particularly in patients with EEG abnormalities or history of such disorders.
Abnormality of the cerebrospinal fluid proteins has also been reported. of a mild urticarial type or photosensitivity are seen. Avoid undue exposure to sun. More severe reactions, including exfoliative dermatitis, have been reported occasionally.
Contact dermatitis has been reported in nursing personnel; accordingly, the use of rubber gloves when administering Chlorpromazine (Chlorpromazine) liquid or injectable is recommended.
In addition, asthma, laryngeal edema, angioneurotic edema and anaphylactoid reactions have been reported.
Mild fever may occur after large I.M. 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:
Chlorpromazine (Chlorpromazine) Overdosage
(See also .)
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.
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. 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 dialyzable.
Chlorpromazine (Chlorpromazine) Dosage And Administration
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.
Chlorpromazine (Chlorpromazine) How Supplied
Chlorpromazine (Chlorpromazine) hydrochloride tablets, USP are available as:
NDC 0615-1546-39 blisterpacks of 30.
NDC 0615-1547 blisterpacks of 30.
For use only in severe neuropsychiatric conditions:
NDC 0615-1548-39 blisterpacks of 30.
Chlorpromazine (Chlorpromazine)
Chlorpromazine (Chlorpromazine) Package Label Principal Display Panel
Chlorpromazine (Chlorpromazine) HCL Tablets,
USP 25mg
Chlorpromazine (Chlorpromazine) Package Label Principal Display Panel
Chlorpromazine (Chlorpromazine) Hydrochloride Tablets,
USP 50mg
Chlorpromazine (Chlorpromazine) Package Label Principal Display Panel
Chlorpromazine (Chlorpromazine) Hydrochloride Tablets,
USP 100mg
