Aminazine

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMINAZIN (AMINAZIN)

Composition:

active substance: chlorpromazine;

1 ml of solution contains 25 mg of chlorpromazine hydrochloride, calculated as 100 % substance;

excipients: anhydrous sodium sulfite (E 221), sodium metabisulfite (E 223), ascorbic acid, sodium chloride, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or slightly yellowish-green liquid.

Pharmacotherapeutic group. Antipsychotics. Phenothiazine derivatives with aliphatic side chain. ATC code N05A A01.

Pharmacological properties.

Pharmacodynamics.

Neuroleptic of the phenothiazine derivatives group. Exhibits pronounced antipsychotic, sedative, and antiemetic effects. Reduces or completely eliminates delusions and hallucinations, suppresses psychomotor agitation, decreases affective reactions, anxiety, restlessness, and reduces motor activity. The mechanism of antipsychotic action is associated with blockade of postsynaptic dopaminergic receptors in the mesolimbic structures of the brain. It also exhibits blocking action on α-adrenergic receptors and suppresses the release of hormones from the pituitary and hypothalamus. However, blockade of dopamine receptors increases pituitary secretion of prolactin. Central antiemetic action is due to inhibition or blockade of dopamine D2-receptors in the chemoreceptor trigger zone of the medulla oblongata; peripheral action is due to blockade of the vagus nerve in the gastrointestinal tract. Sedative action is caused by blockade of central adrenergic receptors. Exhibits moderate or weak effects on extrapyramidal structures.

**Pharmacokin游戏副本

Clinical characteristics.

Indications.

Chronic paranoid and hallucinatory-paranoid states, psychomotor agitation in patients with schizophrenia (hallucinatory-delusional, hebephrenic, catatonic syndromes), alcoholic psychosis, manic excitement in patients with manic-depressive psychosis, mental disorders in patients with epilepsy, agitated depression in patients with presenile and manic-depressive psychosis, as well as other conditions accompanied by excitement and tension. Neurotic disorders associated with increased muscle tone. Persistent pain, including causalgia (in combination with analgesics), persistent sleep disturbances (in combination with hypnotics and tranquilizers). Ménière’s disease, treatment and prevention of vomiting during anticancer therapy and radiation therapy. Dermatological pruritus. As part of lytic mixtures in anesthesiology.

Contraindications.

Hypersensitivity to chlorpromazine or other components of the drug. Liver disorders (cirrhosis, hepatitis, hemolytic jaundice, cholelithiasis), kidney disorders (nephritis, acute pyelitis, renal amyloidosis, urolithiasis), blood disorders, progressive systemic diseases of the central nervous system (slow neuroinfections, e.g. multiple sclerosis), decompensated heart failure, severe cardiovascular diseases, peptic ulcer of the stomach and duodenum during exacerbation, decompensated heart defects, marked arterial hypotension, stroke, thromboembolic disease, severe myocardiodystrophy, rheumatic heart disease in late stages, myxedema, late stage of bronchiectasis, closed-angle glaucoma, urinary retention due to prostatic hyperplasia, pronounced depression of the central nervous system, comatose state, brain injuries, acute infectious diseases. Do not administer simultaneously with barbiturates, alcohol, or narcotics.

Interaction with other medicinal products and other forms of interactions.

The sedative effect of chlorpromazine is enhanced when used concomitantly with zolpidem or zopiclone; the neuroleptic effect is enhanced with estrogens. Plasma concentrations of chlorpromazine are reduced by antacids containing aluminum and magnesium hydroxide (impair absorption from the gastrointestinal tract) and barbiturates (enhance metabolism of chlorpromazine in the liver). Plasma concentrations of chlorpromazine are increased by chloroquine, sulfadoxine/pyrimethamine. Cimetidine may either decrease or increase chlorpromazine plasma concentration. Chlorpromazine may reduce or completely suppress the antihypertensive effect of guanethidine, increase blood concentration of imipramine, inhibit effects of levodopa, increase or decrease blood concentration of phenytoin, and reduce the effect of cardiac glycosides.

Possible interactions when used concomitantly with other medicinal products:

- with anticholinergic agents – enhanced anticholinergic effects;

- with anticholinesterase agents – muscle weakness, worsening of myasthenia gravis;

- with epinephrine – reversal of its effects, leading to further decrease in arterial pressure and development of severe arterial hypotension and tachycardia;

- with amitriptyline – increased risk of developing tardive dyskinesia, possible development of paralytic ileus;

- with diazoxide – pronounced hyperglycemia;

- with doxepin – potentiation of hyperpyrexia;

- with lithium carbonate – severe extrapyramidal symptoms, neurotoxic effects;

- with morphine – development of myoclonus;

- with cisapride – additive prolongation of the QT interval on ECG;

- with nortriptyline in patients with schizophrenia – possible worsening of clinical condition, despite increased blood levels of chlorpromazine;

• with tricyclic antidepressants, maprotiline, monoamine oxidase inhibitors – prolonged and enhanced sedative and anticholinergic effects, increased risk of neuroleptic malignant syndrome;
• with drugs used to treat hyperthyroidism – increased risk of agranulocytosis;
• with other drugs causing extrapyramidal reactions – possible increase in frequency and severity of extrapyramidal disturbances;
• with drugs causing arterial hypotension – possible pronounced orthostatic hypotension;
• with ephedrine – possible weakening of vasoconstrictive effect of ephedrine;
• with other central nervous system (CNS) depressants: morphine derivatives (analgesics, antitussives, substitution therapy), barbiturates, benzodiazepines, other anxiolytics, antihypertensives, ethanol and ethanol-containing preparations – increased CNS depression. Respiratory depression may occur. Reduced attention may make driving or operating machinery hazardous.

In neurotic disorders associated with increased muscle tone, persistent pain including causalgia, chlorpromazine may be combined with analgesics; in persistent insomnia – with hypnotics and tranquilizers.

When used concomitantly with anticonvulsants, the effect of the latter is enhanced and the seizure threshold may be lowered; when used with other agents that depress the central nervous system, as well as with ethanol and ethanol-containing preparations, enhanced CNS depression and respiratory depression may occur.

Barbiturates enhance the metabolism of chlorpromazine by inducing hepatic microsomal enzymes, thereby reducing its plasma concentration and, consequently, its therapeutic effect.

The drug may inhibit the action of amphetamines, levodopa, clonidine, guanethidine, and adrenaline.

Special precautions for use.

The medicinal product is not recommended for patients with hypothyroidism, pheochromocytoma, or myasthenia gravis.

Use with particular caution and under close medical supervision in patients with pathological changes in blood parameters, rheumatism, rheumatic carditis, alcohol intoxication, Reye's syndrome, as well as in patients with breast cancer, severe arterial hypertension, predisposition to glaucoma, Parkinson's disease, chronic respiratory diseases (especially in children), epileptic seizures, moderate cardiovascular diseases, and diabetes mellitus.

Use with caution in elderly patients (increased risk of excessive sedative and hypotensive effects) and in debilitated or weakened patients.

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

In children, especially those with acute illnesses, there is an increased risk of developing extrapyramidal symptoms when using the drug.

During prolonged treatment, regular monitoring of blood parameters, prothrombin index, and liver and kidney function is necessary. After injection, patients should remain lying down for 1–1.5 hours (sudden transition to an upright position may cause orthostatic collapse).

To reduce neuroleptic depression, antidepressants and central nervous system stimulants may be used. During therapy, due to possible photosensitization of the skin, prolonged exposure to sunlight should be avoided. The drug does not exhibit antiemetic effects when nausea results from vestibular stimulation or local irritation of the gastrointestinal tract. In patients with gastrointestinal atony and achylia, administration of gastric juice or hydrochloric acid is recommended concurrently (due to chlorpromazine's inhibitory effect on gastric motility and secretion), and attention should be paid to diet and intestinal function.

Patients receiving this drug may develop an increased need for riboflavin.

Neuroleptic phenothiazines may potentiate QT interval prolongation, increasing the risk of ventricular arrhythmias, including torsades de pointes, which may potentially lead to sudden death. Prior to initiating treatment, patients should be evaluated (biochemical status, ECG) to exclude possible risk factors (e.g., cardiac diseases, history of QT prolongation; metabolic disturbances such as hypokalemia, hypocalcemia, hypomagnesemia; starvation, alcohol abuse, concomitant therapy with other drugs that prolong the QT interval). ECG monitoring is required at the beginning of treatment and, if necessary, during treatment.

This medicinal product contains less than 1 mmol (23 mg)/ml of sodium, i.e., it is practically sodium-free.

This medicinal product contains anhydrous sodium sulfite (E 221) and sodium metabisulfite (E 223), which may rarely cause hypersensitivity reactions and bronchospasm.

When procaine is used as a solvent, information on procaine safety should be taken into account.

Use during pregnancy or breastfeeding.

The medicinal product is not recommended during pregnancy. In cases of acute necessity, treatment duration should be limited, and towards the end of the third trimester, the dose should be reduced if possible. Aminazine prolongs labor.

Newborns whose mothers used antipsychotic agents (including Aminazine) during the third trimester of pregnancy are at risk of developing extrapyramidal symptoms and/or withdrawal symptoms after delivery. Symptoms in newborns may include agitation, increased or decreased muscle tone, tremor, somnolence, respiratory distress, and feeding difficulties. In some newborns, these symptoms resolve within several hours or days and do not require specific treatment. Other newborns may require prolonged hospitalization.

When Aminazine is used in high doses during pregnancy, newborns may occasionally experience gastrointestinal disturbances related to its atropine-like effects and extrapyramidal syndrome.

If use of the drug is necessary, breastfeeding should be discontinued.

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

Ability to affect reaction speed when driving or operating machinery.

During treatment with Aminazine, patients should refrain from driving or operating machinery.

Administration and Dosage.

The medicinal product should be administered intramuscularly and intravenously. The physician determines the dosage and treatment regimen individually, depending on the indications and the patient's condition. For intramuscular administration, the maximum single dose is 150 mg and the daily dose is 600 mg. Typically, 1–5 ml of the solution should be administered intramuscularly, no more than 3 times daily. The treatment course lasts several months; when high doses are used, up to 1.5 months, followed by a transition to maintenance therapy with gradual dose reduction by 25–75 mg per day. In acute mental agitation, administer 100–150 mg (4–6 ml of solution) intramuscularly or 25–50 mg (1–2 ml of Aminazine solution diluted in 20 ml of 5% or 40% glucose solution) intravenously. If necessary, 100 mg (4 ml of solution diluted in 40 ml of glucose solution) may be administered. The injection should be given slowly. For intravenous administration, the maximum single dose is 100 mg and the daily dose is 250 mg.

For intramuscular and intravenous administration in children aged 1 year and older, the single dose is 250–500 mcg/kg of body weight; in children aged 5 years (body weight up to 23 kg), the daily dose is 40 mg; in children aged 5–12 years (body weight 23–46 kg), the daily dose is 75 mg.

In debilitated patients and elderly patients, administer up to 300 mg daily intramuscularly or up to 150 mg daily intravenously.

Children. The drug is contraindicated in children under 1 year of age.

Overdose.

Symptoms: slurred speech, unsteady gait, bradycardia, labored breathing, marked weakness, confusion, diminished reflexes, drowsiness, seizures, persistent hypotension, hypothermia, prolonged depression, and later— toxic hepatitis.

Treatment: symptomatic therapy. There is no specific antidote. The drug is not removed by hemodialysis. In collapse-like conditions, administration of cordiamine, caffeine, or mesaton is recommended. If dermatitis develops, Aminazine therapy should be discontinued and antihistamines prescribed. Neurological complications usually diminish with dose reduction of Aminazine; they can also be reduced by a single dose of cyclodol or other corrective agents.

After prolonged use of high doses of the drug (0.5–1.5 g daily), jaundice, accelerated blood coagulation, lymphopenia and leukopenia, anemia, agranulocytosis, skin pigmentation, and opacification of the lens and cornea may be observed in isolated cases.

Adverse Reactions.

Central nervous system: With prolonged use, development of neuroleptic syndrome is possible: parkinsonism, akathisia, mental indifference, and other psychic disturbances; delayed response to external stimuli, blurred vision; dystonic extrapyramidal reactions, tardive dyskinesia, neuroleptic depression, thermoregulation disorders, malignant neuroleptic syndrome; seizures, insomnia, excitement, delirium, drowsiness, nightmares, depression.

Cardiovascular system: Possible arterial hypotension (especially with intravenous administration), tachycardia; ECG changes (prolongation of QT interval, ST-segment depression, changes in T and U waves, arrhythmia).

Gastrointestinal system: Cholestatic jaundice, nausea, vomiting, dry mouth, constipation.

Hematopoietic system: Leukopenia, agranulocytosis, hematological changes, eosinophilia.

Urinary system: Difficulty in urination, priapism.

Endocrine system: Menstrual cycle disturbances, impotence, gynecomastia, weight gain, galactorrhea, hyperprolactinemia, hyperglycemia, impaired glucose tolerance, hypercholesterolemia.

Immune system: Hypersensitivity reactions, including skin rashes, pruritus, bronchospasm, urticaria, angioedema, erythema multiforme, exfoliative dermatitis, systemic lupus erythematosus, and other allergic reactions.

Skin and mucous membranes: When solutions come into contact with mucous membranes, skin, or subcutaneous tissue – tissue irritation: reactions at the injection site, including painful infiltrates, endothelial damage, and others. Skin pigmentation, photosensitization. To prevent these effects, chlorpromazine solution should be diluted with procaine solutions, glucose, or 0.9% sodium chloride solution.

Eyes: With prolonged use at high doses, deposition of chlorpromazine in the anterior eye structures (cornea and lens) may occur, which can accelerate the natural aging processes of the lens, miosis.

Respiratory system: Nasal congestion.

General: Isolated reports of sudden death associated with drug intake.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibility.

Do not mix with other medicinal products in the same syringe.

Packaging.

2 ml in an ampoule; 10 ampoules per box.

2 ml in an ampoule; 5 ampoules in a blister pack, 2 blisters per box.

2 ml in an ampoule; 10 ampoules in a blister pack; 1 blister pack per box.

Prescription status.

By prescription only.

Manufacturer.

Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorov'ya Narodu".

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and location of business activity.

Ukraine, 61002, Kharkiv region, Kharkiv city, Kulikivska Street, 41.

(Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorov'ya Narodu")

Ukraine, 61013, Kharkiv region, Kharkiv city, Shevchenka Street, 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA")