Chlorpromazine (Tablets, Solution) Instructions for Use

ATC Code

N05AA01 (Chlorpromazine)

Active Substance

Chlorpromazine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Psycholeptics; antipsychotics; aliphatic phenothiazine derivatives

Pharmacological Action

Chlorpromazine is an antipsychotic agent (neuroleptic) from the group of phenothiazine derivatives. It has a pronounced antipsychotic, sedative, and antiemetic effect. It weakens or completely eliminates delusions and hallucinations, relieves psychomotor agitation, reduces affective reactions, anxiety, restlessness, and decreases motor activity.

The mechanism of antipsychotic action is associated with the blockade of postsynaptic dopaminergic receptors in the mesolimbic structures of the brain. It also has a blocking effect on α-adrenergic receptors and suppresses the release of hormones from the pituitary and hypothalamus. However, the blockade of dopamine receptors increases the secretion of prolactin by the pituitary gland.

The central antiemetic effect is due to the inhibition or blockade of dopamine D₂ receptors in the chemoreceptor trigger zone of the cerebellum; the peripheral effect is due to the blockade of the vagus nerve in the gastrointestinal tract. The antiemetic effect is enhanced, apparently, due to anticholinergic, sedative, and antihistamine properties. The sedative effect is likely due to alpha-adrenergic blocking activity. It has a moderate or weak extrapyramidal effect.

Pharmacokinetics

When taken orally, Chlorpromazine is rapidly but sometimes incompletely absorbed from the gastrointestinal tract. C_max in blood plasma is reached in 2-4 hours. It undergoes a significant first-pass effect through the liver. Due to this effect, plasma concentrations after oral administration are lower than concentrations after intramuscular administration.

It is intensively metabolized in the liver with the formation of a number of active and inactive metabolites.

The metabolic pathways of chlorpromazine include hydroxylation, conjugation with glucuronic acid, N-oxidation, oxidation of sulfur atoms, and dealkylation.

Chlorpromazine has high binding to plasma proteins (95-98%). It is widely distributed in the body, penetrates the blood-brain barrier, with the concentration in the brain being higher than in plasma.

Significant variability in pharmacokinetic parameters has been noted in the same patient. There is no direct correlation between the plasma concentrations of chlorpromazine and its metabolites and the therapeutic effect.

The T_1/2 of chlorpromazine is about 30 hours; it is believed that the elimination of its metabolites may be more prolonged. It is excreted in the urine and bile in the form of metabolites.

Indications

Chronic paranoid and hallucinatory-paranoid states, states of psychomotor agitation in schizophrenia (hallucinatory-delusional, hebephrenic, catatonic syndromes), alcoholic psychosis, manic agitation in manic-depressive psychosis, mental disorders in epilepsy, agitated depression in patients with presenile psychosis, manic-depressive psychosis, as well as other diseases accompanied by agitation and tension. Neurotic diseases accompanied by increased muscle tone. Persistent pain, including causalgia (in combination with analgesics), persistent sleep disorders (in combination with hypnotics and tranquilizers). Meniere’s disease, vomiting of pregnancy, treatment and prevention of vomiting during treatment with antineoplastic agents and during radiation therapy. Itching dermatoses. As part of “lytic mixtures” in anesthesiology.

ICD codes

Dosage Regimen

Establish the dosage individually based on indication, severity, and patient response.

For oral administration, initiate therapy with a low dose. Titrate the dose gradually upward.

For adult outpatients with psychosis, initiate at 25-50 mg two to three times daily.

For hospitalized adult patients, a starting dose of 50-100 mg two to three times daily is typical.

Increase the dose by 25-50 mg every two to three days until effective control of symptoms is achieved.

The usual maintenance dose for antipsychotic effect ranges from 300 mg to 800 mg daily in divided doses.

Some patients may require doses up to 1-2 grams daily for severe conditions.

For nausea and vomiting, administer 10-25 mg every four to six hours as needed.

For intractable hiccups, use 25-50 mg three to four times daily.

For acute intermittent porphyria, administer 25-50 mg three to four times daily.

In geriatric or debilitated patients, initiate therapy with one-third to one-half the usual adult dose.

Increase doses more slowly and use the lowest effective maintenance dose.

For pediatric patients, base the dose on body weight. The usual dose is 0.5-1 mg/kg every four to six hours as needed.

For children aged 6 months to 12 years, the total daily dose for psychosis or nausea typically should not exceed 500 mg.

For children over 12 years, do not exceed the total adult daily dose.

Administer the total daily dose in divided doses, typically two to four times per day.

Administer with food or a full glass of water or milk to minimize gastrointestinal irritation.

Avoid abrupt discontinuation after long-term use. Taper the dose gradually to prevent withdrawal symptoms or rapid symptom recurrence.

Monitor for adverse effects, particularly extrapyramidal symptoms, sedation, and orthostatic hypotension, especially during dose titration.

Regularly reassess the need for continued therapy and the appropriateness of the current dosage.

Adverse Reactions

From the central nervous system: akathisia, blurred vision are possible; rarely – dystonic extrapyramidal reactions, parkinsonian syndrome, tardive dyskinesia, thermoregulation disorders, neuroleptic malignant syndrome; in isolated cases – seizures.

From the cardiovascular system: arterial hypotension (especially with intravenous administration), tachycardia are possible.

From the digestive system: dyspeptic phenomena (when taken orally) are possible; rarely – cholestatic jaundice.

From the hematopoietic system: rarely – leukopenia, agranulocytosis.

From the urinary system: rarely – difficulty urinating.

From the endocrine system: menstrual cycle disorders, impotence, gynecomastia, increased body weight.

Allergic reactions: skin rash, itching are possible; rarely – exfoliative dermatitis, erythema multiforme.

Dermatological reactions: rarely – skin pigmentation, photosensitivity.

From the organ of vision: with long-term use in high doses, deposition of chlorpromazine in the anterior structures of the eye (cornea and lens) is possible, which may accelerate the processes of normal lens aging.

Contraindications

Impaired liver function, kidney function, hematopoietic organs, progressive systemic diseases of the brain and spinal cord, myxedema, severe cardiovascular diseases, thromboembolic disease; late stage of bronchiectasis; angle-closure glaucoma; urinary retention associated with prostatic hyperplasia; pronounced central nervous system depression, coma, brain trauma.

Use in Pregnancy and Lactation

If it is necessary to use chlorpromazine during pregnancy, the duration of treatment should be limited, and at the end of pregnancy, if possible, the dose should be reduced. It should be borne in mind that Chlorpromazine prolongs labor.

If it is necessary to use during lactation, breastfeeding should be discontinued.

Chlorpromazine and its metabolites cross the placental barrier and are excreted in breast milk.

Clinical studies have shown that Chlorpromazine may have a teratogenic effect. When chlorpromazine was used in high doses during pregnancy, newborns in some cases experienced digestive disorders associated with atropine-like effects, extrapyramidal syndrome.

Use in Hepatic Impairment

Contraindicated in impaired liver function.

Use in Renal Impairment

Contraindicated in impaired kidney function.

Pediatric Use

Use in children is possible according to the dosing regimen.

In children, especially with acute illnesses, the development of extrapyramidal symptoms is more likely when using phenothiazines.

Geriatric Use

Phenothiazines should be used with caution in elderly patients (increased risk of excessive sedative and hypotensive effects).

Special Precautions

Phenothiazines should be used with particular caution in patients with pathological changes in the blood picture, impaired liver function, alcohol intoxication, Reye’s syndrome, as well as in breast cancer, cardiovascular diseases, predisposition to the development of glaucoma, Parkinson’s disease, gastric and duodenal ulcers, urinary retention, chronic respiratory diseases (especially in children), epileptic seizures.

Phenothiazines should be used with caution in elderly patients (increased risk of excessive sedative and hypotensive effects), in debilitated and weakened patients.

In case of hyperthermia, which is one of the symptoms of neuroleptic malignant syndrome, Chlorpromazine should be discontinued immediately.

In children, especially with acute illnesses, the development of extrapyramidal symptoms is more likely when using phenothiazines.

During treatment, alcohol consumption is not allowed.

Effect on the ability to drive vehicles and operate machinery

It should be used with caution in patients engaged in potentially hazardous activities that require a high speed of psychomotor reactions.

Drug Interactions

With simultaneous use of drugs that have a depressant effect on the central nervous system, ethanol, and ethanol-containing drugs, an increase in the depressant effect on the central nervous system, as well as respiratory depression, is possible.

With simultaneous use of tricyclic antidepressants, maprotiline, MAO inhibitors, an increased risk of developing neuroleptic malignant syndrome is possible.

With simultaneous use with anticonvulsants, a decrease in the seizure threshold is possible; with agents for the treatment of hyperthyroidism – an increased risk of developing agranulocytosis; with drugs that cause extrapyramidal reactions – an increase in the frequency and severity of extrapyramidal disorders is possible; with drugs that cause arterial hypotension – an additive effect on blood pressure is possible, leading to pronounced arterial hypotension, increased orthostatic hypotension.

With simultaneous use with amphetamines, antagonistic interaction is possible; with anticholinergic agents – enhancement of the anticholinergic effect; with anticholinesterase agents – muscle weakness, worsening of myasthenia gravis.

With simultaneous use with antacids containing aluminum and magnesium hydroxide, the concentration of chlorpromazine in blood plasma decreases due to impaired absorption from the gastrointestinal tract.

With simultaneous use, barbiturates enhance the metabolism of chlorpromazine by inducing liver microsomal enzymes and thereby reducing its plasma concentrations.

With simultaneous use of oral hormonal contraceptives, a case of increased plasma concentration of chlorpromazine has been described.

With simultaneous use with epinephrine, a “reversal” of the pressor effect of epinephrine is possible, as a result, only stimulation of β-adrenergic receptors occurs and severe hypotension and tachycardia occur.

With simultaneous use with amitriptyline, the risk of developing tardive dyskinesia increases. Cases of paralytic ileus have been described.

With simultaneous use, Chlorpromazine may reduce or even completely suppress the antihypertensive effect of guanethidine, although in some patients the hypotensive effect of chlorpromazine may be manifested.

With simultaneous use with diazoxide, severe hyperglycemia is possible; with doxepin – potentiation of hyperpyrexia; with zolpidem – the sedative effect is significantly enhanced; with zopiclone – an increase in the sedative effect is possible; with imipramine – the plasma concentration of imipramine increases.

With simultaneous use, Chlorpromazine suppresses the effects of levodopa due to the blockade of dopamine receptors in the central nervous system. An increase in extrapyramidal symptoms is possible.

With simultaneous use with lithium carbonate, severe extrapyramidal symptoms and neurotoxic effects are possible; with morphine – the development of myoclonus is possible.

With simultaneous use of nortriptyline in patients with schizophrenia, a worsening of the clinical condition is possible, despite an increased level of chlorpromazine in the blood plasma. Cases of paralytic ileus have been described.

With simultaneous use with piperazine, a case of seizure development has been described; with propranolol – an increase in plasma concentrations of propranolol and chlorpromazine; with trazodone – arterial hypotension is possible; with trihexyphenidyl – there are reports of the development of paralytic ileus; with trifluoperazine – cases of severe hyperpyrexia have been described; with phenytoin – an increase or decrease in the plasma concentration of phenytoin is possible.

With simultaneous use with fluoxetine, the risk of developing extrapyramidal symptoms increases; with chloroquine, sulfadoxine/pyrimethamine, the plasma concentration of chlorpromazine increases with the risk of developing toxic effects of chlorpromazine.

With simultaneous use of cisapride, the QT interval on the ECG is additively prolonged.

With simultaneous use with cimetidine, a decrease in the plasma concentration of chlorpromazine is possible. There are also data suggesting an increase in the plasma concentration of chlorpromazine.

With simultaneous use with ephedrine, a weakening of the vasoconstrictor effect of ephedrine is possible.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.