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Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Chlorpromazine hydrochloride oral solutions, tablets, and injection should be stored at a temperature less than 40 °C, preferably between 15-30 °C; freezing of the oral solutions and injection should be avoided. ... Chlorpromazine suppositories should be stored in well-closed containers between 15-30 °C. ...Chlorpromazine hydrochloride oral concentrate solution should be dispensed in amber glass bottles.

Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Use safety glasses or goggles and protect exposed skin.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Engineering controls such as exhaust ventilation are recommended.

Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

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 Benadryl. 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, Levophed and Neo-Synephrine 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. (L1712)

... Dosage requirements for oral hypoglycemic agents may be increased in those receiving chlorpromazine ... .

QT interval-prolonging medications, including cisapride, erythromycin, and quinidine /may produce/ additive QT interval prolongation increasing the risk of developing cardiac arrhythmias when /concurrently administered with phenothiazines/. /Phenothiazines/

Concurrent use /of other photosensitizing medications/ with phenothiazines may cause additive photosensitizing effects. In addition, concurrent use of systemic methoxsalen, trixsalen, or tetracyclines with phenothiazines may potentiate intraocular photochemical damage to the choroid, retina, or lens. /Phenothiazines/

Prior administration of phenothiazines may decrease the pressor effect and shorten the duration of action of phenylephrine. /Phenothiazines/

For more Interactions (Complete) data for Chlorpromazine (37 total), please visit the HSDB record page.

Liver test abnormalities have been reported to occur in up to 40% of patients on long term therapy with chlorpromazine, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually self-limited and unaccompanied by symptoms, reversing even without discontinuation.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9,900(SRC), determined from a log Kow of 5.41(2) and a regression-derived equation(3), indicates that chlorpromazine is expected to be immobile in soil(SRC). The pKa of chlorpromazine is 9.3(4), indicating that this compound will almost entirely exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the base exists as an cation and cations do not volatilize. Chlorpromazine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.17X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2010).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9,900(SRC), determined from a log Kow of 5.41(2) and a regression-derived equation(3), indicates that chlorpromazine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.3(4) indicates chlorpromazine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(5), an estimated BCF of 1,700(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2010).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), chlorpromazine, which has an estimated vapor pressure of 5.17X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase chlorpromazine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.6 hours(SRC), calculated from its rate constant of 2.45X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase chlorpromazine may be removed from the air by wet or dry deposition(SRC). Chlorpromazine does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Dermatotoxin - PACD (photoallergic contact dermatitis).

Chlorpromazine is a low-potency antipsychotic that mainly causes non-neurologic side effects. It is highly lipid-soluble and stored in body fats, thus very slow to be removed from the body. Being a low-potency typical antipsychotic, it primarily causes dry mouth, dizziness, urine retention, blurred vision, and constipation by blocking the muscarinic receptors. There is a risk of angle-closure glaucoma in older patients. It also causes sedation due to the blockade of histamine H1 receptors.

IDENTIFICATION: Chlorpromazine is an antipsychotic medication. It is a synthetic dimethylamine derivative of phenothiazine. Chlorpromazine is a white to creamy-white (Base and hydrochloride). Powder or waxy solid (Base); crystallline powder (Hydrochloride). Chlorpromzaine is practically insoluble in water. Freely soluble in dilute mineral acids; practically insoluble in dilute alkali hydroxides. HUMAN EXPOSURE: Main risks and target organs: The principal pharmacological actions are psychotropic. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system, primarily at subcortical levels, as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weak peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity. Summary of clinical effects: Central nervous depression may progress from drowsiness to coma, ultimately with areflexia. In early or mild intoxications, some patients suffer from restlessness, confusion and excitement. Tremor or muscular twitching, spasm, rigidity, convulsions, muscular hypotonia, difficulty in swallowing may be present. Extrapyramidal signs of overdose include dystonia, torticollis, oculogyric crises and opisthotonos. Either hypothermia or hyperthermia may be encountered. Difficulty in breathing, cyanosis, respiratory and/or vasomotor collapse, respiratory depression and distress, sudden apnea and even cyanosis may occur. Hypotension, tachycardia, cardiac arrhythmias, conduction defects, ventricular fibrillation or cardiac arrest may occur. Contraindications: Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, anesthetics, narcotics, etc.) because chlorpromazine prolongs and intensifies the action of such CNS depressants. Chlorpromazine should be administered cautiously to persons with cardiovascular or liver disease. There is evidence that patients with a history of hepatic encephalopathy due to cirrhosis have increased sensitivity to the CNS effect of chlorpromazine (e.g. impaired cerebration and abnormal slowing of the EEG). Because of this CNS depressant effect, it should be used with caution in patients with chronic respiratory disorders such as severe asthma, emphysema and acute respiratory infections, particularly in children. Because it can suppress the cough reflex, aspiration of vomitus is possible. Subcutaneous injection is contraindicated. Routes of entry: Oral: Chlorpromazine is available in tablet or syrup forms for oral ingestion. Parenteral: It is present in injectable forms for use through the intramuscular or intravenous routes. Other: Rectal route with suppositories. Absorption by route of exposure: The absorption of orally administered chlorpromazine is dependent on the dosage form, the elixir giving the highest plasma concentration of drug. Peak plasma levels are reached at 2 to 3 hours. There is a wide inter-subject variability (ten times or more) in the plasma concentrations achieved. Plasma concentrations may be decreased significantly by food in the stomach and by the concomitant administration of anticholinergic antiparkinsonism drugs. Owing to the first-pass effect, plasma concentrations following oral administrations are much lower than those following intramuscular administrations. Distribution by route of exposure: Chlorpromazine is widely distributed in the body and crosses the blood-brain barrier to achieve higher concentrations in the brain than in the plasma. Chlorpromazine and its metabolites also cross the placental barrier and are excreted in milk. Chlorpromazine is highly bound to plasma proteins, varying from 91.8% to 97% over the range of clinical blood concentrations (0.01 to 1 mcg/mL). Binding is easily reversed. Biological half-life by route of exposure: Although the plasma half-life of chlorpromazine itself has been reported to be only a few hours, elimination of the metabolites may be very prolonged. Blood studies show a range of 2 to 3 days and for the urinary studies up to about 18 days. Chlorpromazine brings about changes that can persist much longer than these times after discontinuation of the drug. The exact relationship of persisting therapeutic effects to administered chlorpromazine is uncertain. There is the possibility that minute amounts of chlorpromazine and/or metabolites persist at active sites in slowly reversible or relatively irreversible ways. It also seems that some chlorpromazine is stored in adipose tissue and slowly mobilized after stopping chlorpromazine administration. Metabolism: Paths of metabolism of chlorpromazine include hydroxylation, and conjugation with glucuronic acid, N-oxidation, oxidation of a sulfur atom, and dealkylation. In man, after chronic use, the highest concentration of unconjugated chlorpromazine metabolites is found in the lung and liver. The 7-hydroxy chlorpromazine that is found in body tissues appears to be an active metabolite. Since there is some evidence that chlorpromazine can cause hepatic microsomal enzyme induction, it may accelerate its own metabolism; this may account for progressively decreasing plasma concentrations of free drug during maintenance of a fixed dosage schedule. One hundred and sixty-eight possible metabolites of chlorpromazine have been postulated and many of them actually isolated from human urine. In man, urinary excretion of chlorpromazine plus its sulfoxides varies from 1 to 20% of the daily dose administered. The average ratio of free chlorpromazine to the sulfoxide in the urine is about 1:16. There is much evidence that the sulfoxide undergoes additional metabolism, probably to sulfones. The various phenothiazine congeners of chlorpromazine undergo similar metabolic degradation. Demethylation is another method of detoxication by the liver. Elimination by route of exposure: Chlorpromazine is excreted in both urine and feces. Mode of action: Chlorpromazine has a wide range of activity arising from its depressant actions on the central nervous system and its alpha-adrenergic blocking and weak antimuscarinic activities. Chlorpromazine possesses sedative properties but patients usually develop tolerance rapidly to the sedation. Its action on the autonomic system produces vasodilation, hypotension, and tachycardia. Salivary and gastric secretions are reduced. The sulfoxides of the phenothiazines have been intensively studied and found to be significantly less potent than the parent compound. Teratogenicity: If given in high doses over a long period during pregnancy, chlorpromazine may cause damage to the retina of the fetus. Interactions: Chlorpromazine may block the antihypertensive effects of guanethidine. Patients being treated with phenothiazines should be advised that their susceptibility to alcohol may be increased. Chlorpromazine has been shown to increase the miotic and sedative effects of morphine. Chlorpromazine may enhance the respiratory depression produced particularly by CNS depressants. Mutual inhibition of liver enzymes concerned with the metabolism of both chlorpromazine and the other drug (e.g. a tricyclic antidepressant) might result in increased plasma-concentrations of either drug. Chlorpromazine is reported to interfere with a number of laboratory tests, such as pregnancy tests, thyroid function tests, the Coombs' test where a false positive result can be achieved, and adrenal medullary tests. It is also reported to interfere with estimations for serum 5-hydroxyindole-acetic acid, blood urea, urinary ketones and steroids, urinary porphobilinogen, and vitamin B12. Main adverse effects: Therapeutic doses of chlorpromazine, may cause palpitation, nasal stuffiness, dry mouth, and slight constipation. The patient may complain of being cold, drowsy, or weak. Orthostatic hypotension, which may result in syncope. A mild elevation of temperature may be seen during the first few days, particularly if the drug is given parenterally. On the other hand, hypothermia can occur and may be due both to the action on the heat regulating center and to direct peripheral vasodilation. Sensitivity and adaptation to environmental temperature change are impaired so that fatal hyperthermia and heat stroke are possible complications. Chlorpromazine has produced hematological disorders, including agranulocytosis, eosinophilia, leucopenia, hemolytic anemia, aplastic anemia, thrombocytopenic purpura and pancytopenia. Hyperglycemia, hypoglycemia and glycosuria have also been reported.

The Koc of chlorpromazine is estimated as 9,900(SRC), using a log Kow of 5.41(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that chlorpromazine is expected to be immobile in soil. The pKa of chlorpromazine is 9.3(4), indicating that this compound will almost entirely exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/HUMAN EXPOSURE STUDIES/ Sudden and unexpected deaths have occurred in patients receiving phenothiazines, especially during long-term administration of the drugs. In some patients, sudden death appeared to result from asphyxia (secondary to failure of the cough reflex) or cardiac arrest. /Phenothiazines/

/SIGNS AND SYMPTOMS/ In general, overdosage of phenothiazines may be expected to produce effects that are extensions of common adverse reactions; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. CNS depression progressing to coma with areflexia or CNS stimulation with convulsions followed by respiratory depression may occur; patients with early or mild intoxication may experience drowsiness, restlessness, disorientation, confusion, and excitement. Other reported effects associated with acute phenothiazine overdosage have included shock (eg, ECG changes and cardiac arrhythmias), increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, bilateral bundle branch block, atrioventricular block, ventricular tachycardia, ventricular fibrillation, torsades de pointes, myocardial depression, agitation, dry skin, nasal congestion, urinary retention, oliguria, uremia, blurred vision, hypothermia, hyperthermia, mydriasis, miosis, tremor, muscle twitching, spasm or rigidity, seizures, muscular hypotonia, constipation, ileus, dry mouth, vomiting, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, and pulmonary edema, possibly with sudden apnea. /Phenothiazine general Statement/

/SIGNS AND SYMPTOMS/ Fatalities in infants have resulted from chlorpromazine ingestion as low as 350 mg, whereas adult death has occurred from consumption of 2 g. Survival in an adult has been associated with 10 and 17 g ingestions. Hypotension and lethargy in toddlers can follow chlorpromazine dosages ranging from 100 to 375 mg, and serious central nervous depression may result from doses of 200 to 1,200 mg. Adult response to chlorpromazine ingestion is highly variable, but significant central nervous system depression can be expected from doses exceeding 5 g. ... In addition ... chlorpromazine, ... /has/ been implicated in sudden death when administered to psychotic patients at therapeutic doses.

/SIGNS AND SYMPTOMS/ An extrapyramidal syndrome (EPS), which may persist for months, has been observed in some infants whose mothers received chlorpromazine near term. This reaction is characterized by tremors, increased muscle tone with spasticity, and hyperactive deep tendon reflexes. Hypotonicity has been observed in one newborn and paralytic ileus in two after exposure at term to chlorpromazine.

For more Human Toxicity Excerpts (Complete) data for Chlorpromazine (37 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including chlorpromazine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Chlorpromazine hydrochloride/

Medication (antipsychotic drug)

... in the treatment of intractable hiccup

THERAPEUTIC CATEGORY: Antiemetic; antipsychotic

THERAPEUTIC CATEGORY (VETERINARY): Antiemetic; tranquilizer

MEDICATION (VET)

For the treatment of schizophrenia, control nausea and vomiting, For relief of restlessness and apprehension before surgery, adjunct in the treatment of tetanus, control the manifestations of the manic type of manic-depressive illness.

(1972) 5.0X10+4 GRAMS (PRINCPL CUSTMS DISTS)

(1975) 1.31X10+6 GRAMS (PRINCPL CUSTMS DISTS)

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

Chlorpromazine Hydrochloride preparations: (AHFS, 2010)

Chlorpromazine preparations: (AHFS, 2010)

Rectal suppositories 25 or 100 mg

Oral capsules, extended release 30, 75, 150, 200, and 300 mg; Solution 10 mg/5 mL; Solution, concentrate 30 mg/mL and 100 mg/mL.

Veterinary Drug -> TRANQUILLIZING_AGENT -> JECFA Functional Classes

Pharmaceuticals

Chlorpromazine increases the miotic and sedative effects of morphine and may increase its analgesic actions.

Chlorpromazine was first demonstrated in anesthesiology and in the treatment of operative show as an "automatic stabilizer" ... it was the first representative of a new class of drugs to treat psychoses, namely the major tranquilizers (neuroleptics).