Neuleptil^® (Capsules, Solution) Instructions for Use

ATC Code

N05AC01 (Periciazine)

Active Substance

Periciazine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Psycholeptics; antipsychotics; piperazine phenothiazine derivatives

Pharmacological Action

Periciazine is a neuroleptic from the group of piperidine derivatives of phenothiazine, whose antidopaminergic activity determines the development of the therapeutic antipsychotic (without a stimulating component), as well as antiemetic and hypothermic effects of the drug. However, the development of its side effects (extrapyramidal syndrome, movement disorders and hyperprolactinemia) is also associated with antidopaminergic activity.

The antidopaminergic activity of periciazine is moderately pronounced, due to which it has a moderate antipsychotic effect with a moderate severity of extrapyramidal disorders. Due to the blocking effect of periciazine on the adrenoreceptors of the reticular formation of the brainstem and central histamine receptors, the drug has a pronounced sedative effect, which can also be a desirable clinical effect, especially with angry-irritable and irascible types of affect, and the reduction of aggressiveness is not accompanied by the occurrence of lethargy and inhibition. Compared with chlorpromazine, Periciazine has a more pronounced antiserotonin, antiemetic and central sedative effect, but a less pronounced antihistamine effect.

Periciazine reduces aggressiveness, excitability, disinhibition, due to which it is effective in behavioral disorders. Due to the normalizing effect on behavior, Periciazine has received the name “behavior corrector”.

Blockade of peripheral histamine H₁-receptors determines the antiallergic effect of the drug. Blockade of peripheral adrenergic structures is manifested by its hypotensive action. In addition, the drug has anticholinergic activity.

Pharmacokinetics

Absorption

After oral administration, Periciazine is well absorbed; however, like other phenothiazine derivatives, it undergoes intensive presystemic metabolism in the intestine and/or liver, so after its oral administration, the concentration of unchanged periciazine in plasma is lower than with intramuscular administration and varies widely.

After oral administration of 20 mg of periciazine, C_max in plasma is reached within 2 hours and is 150 ng/ml (410 nmol/l).

Distribution

Plasma protein binding is 90%. Periciazine intensively penetrates into tissues, as it easily passes through histohematic barriers, including the BBB.

Metabolism

Most of the periciazine is metabolized in the liver by hydroxylation and conjugation.

Elimination

Metabolites excreted with bile can be reabsorbed in the intestine. T_1/2 of periciazine is 12-30 hours; the elimination of metabolites is even longer. Conjugated metabolites are excreted in the urine, the rest of the drug and its metabolites are excreted in bile and feces.

Pharmacokinetics in special patient groups

In elderly patients, the metabolism and excretion of phenothiazines is slowed down.

Indications

Adults aged 18 years and over

• Acute psychotic disorders;
• Chronic psychotic disorders, such as schizophrenia, chronic non-schizophrenic delusional disorders (paranoid delusional disorders, chronic hallucinatory psychoses) (for treatment and relapse prevention);
• Anxiety, psychomotor agitation, aggressive or dangerous impulsive behavior (as an additional drug for the short-term treatment of these conditions).

Children over 3 years old

• Severe behavioral disorders with agitation and excitability.

ICD codes

Dosage Regimen

Capsules

The drug Neuleptil^®, capsules 10 mg, is intended for adult patients. In children, the drug Neuleptil^®, oral solution 4%, should be used.

The dosage regimen varies significantly depending on the indications and the patient’s condition. Doses of the drug should be selected individually. If the patient’s condition allows, treatment should be started with low doses, which can then be gradually increased. The minimum effective dose should always be used.

The daily dose should be divided into 2 or 3 doses, the larger part of the dose should always be taken in the evening.

The daily dose can vary from 30 mg to 100 mg. The maximum daily dose is 200 mg.

Treatment of acute and chronic psychotic disorders

The initial daily dose is 70 mg (divided into 2-3 doses). The daily dose can be increased by 20 mg per week until the optimal effect is achieved (on average up to 100 mg/day).

In exceptional cases, the daily dose can be increased to 200 mg.

Treatment of anxiety, psychomotor agitation, aggressive or dangerous impulsive behavior

Neuleptil^® is used as an additional drug for short-term treatment.

The initial daily dose is 10-30 mg (divided into 2 doses). The duration of short-term treatment is determined by the doctor.

Elderly patients

For all indications, doses should be reduced by 2-4 times.

Solution

Orally.

The dosage regimen varies significantly depending on the indications and the patient’s condition. Doses of the drug should be selected individually. If the patient’s condition allows, treatment should be started with low doses, which can then be gradually increased. The minimum effective dose should always be used.

The daily dose should be divided into 2 or 3 doses, the larger part of the dose should always be taken in the evening.

The 30 ml bottle has a dropper that allows you to measure the amount of the drug based on the fact that 1 drop contains 1 mg of periciazine.

The packaging with 125 ml bottles includes a dosing device with a graduated scale that allows you to measure the amount of the drug, starting from a dose of 10 mg and up to a maximum of 150 mg.

Dosing of the drug is carried out in mg.

1 ml of the medicinal product contains 40 mg of the active substance.

Adults

The daily dose can vary from 30 mg to 100 mg.

The maximum daily dose is 200 mg.

Treatment of acute and chronic psychotic disorders

The initial daily dose is 75 mg (divided into 2-3 doses). The daily dose can be increased by 25 mg per week until the optimal effect is achieved (on average up to 100 mg/day). In exceptional cases, the daily dose can be increased to 200 mg.

Treatment of anxiety, psychomotor agitation, aggressive or dangerous impulsive behavior

Neuleptil^® is used as an additional drug for short-term treatment.

The initial daily dose is 15-30 mg (divided into 2 doses). The duration of short-term treatment is determined by the doctor.

In elderly patients, doses for all indications should be reduced by 2-4 times.

Children from 3 to 18 years old

Treatment of severe behavioral disorders with agitation and excitability

The daily dose is 0.1-0.5 mg/kg of body weight per day.

Adverse Reactions

Adverse reactions are grouped according to the MedDRA classification of organ systems and frequency of occurrence. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥ 1/100, but < 1/10); uncommon (≥ 1/1000, but < 1/100); rare (≥ 1/10000, but < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from the available data).

Blood and lymphatic system disorders frequency not known – agranulocytosis, leukopenia, eosinophilia, thrombocytopenia (including thrombocytopenic purpura).

Immune system disorders frequency not known – hypersensitivity, urticaria, angioedema.

Endocrine disorders frequency not known – hyperprolactinemia (which may lead to amenorrhea, galactorrhea, gynecomastia, erectile dysfunction), thermoregulation disorders.

Metabolism and nutrition disorders frequency not known – impaired glucose tolerance, hyperglycemia, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion.

Psychiatric disorders frequency not known – apathy, confusion, delirium, anxiety, mood changes.

Nervous system disorders (when used in high doses) common – parkinsonism; frequency not known – dystonia (including spasmodic torticollis, oculogyric crises, trismus), tardive dyskinesia with long-term treatment (anticholinergic antiparkinsonian drugs are ineffective and may lead to worsening), extrapyramidal syndrome (akinesia with or without hypertonia, partially relieved by anticholinergic antiparkinsonian drugs; hyperkinetic-hypertonic and expiratory motor activity; akathisia), sedation or drowsiness, dizziness, insomnia, neuroleptic malignant syndrome, effects due to blockade of m-cholinergic receptors (dry mouth, accommodation disturbance, urinary retention, constipation, paralytic ileus), seizures.

Eye disorders frequency not known – accommodation disturbance, brownish deposits in the anterior segment of the eye, due to accumulation of the drug, usually not affecting vision.

Cardiac disorders there are reports of sudden death, possibly associated with cardiac disorders, as well as cases of unexplained sudden death in patients taking neuroleptics from the group of phenothiazine derivatives; frequency not known – bidirectional ventricular tachycardia (torsades de pointes type arrhythmia), ECG abnormalities, which include QT interval prolongation (as with other neuroleptics), ST segment depression, appearance of pathological U wave and T wave changes. During treatment with phenothiazine derivatives, possibly dose-dependent cardiac arrhythmias have been reported, including ventricular and atrial arrhythmias, AV block and ventricular tachycardia, which can lead to ventricular fibrillation and cardiac arrest.

Vascular disorders when using neuroleptics, cases of venous thromboembolic complications have been reported, including pulmonary embolism (sometimes fatal) and cases of deep vein thrombosis; frequency not known – orthostatic hypotension (more common in elderly patients and patients with reduced blood volume).

Respiratory, thoracic and mediastinal disorders: frequency not known – respiratory depression, nasal congestion.

Hepatobiliary disorders very rare – cholestatic jaundice and liver damage.

Skin and subcutaneous tissue disorders frequency not known – skin reactions, skin rash, photosensitivity, pigmentation disorders.

Pregnancy, puerperium and perinatal conditions frequency not known – neonatal withdrawal syndrome.

Reproductive system and breast disorders very rare – priapism, ejaculation disorder.

Investigations frequency not known – positive serological test for antinuclear antibodies without clinical manifestations of lupus erythematosus, weight gain, abnormal liver function tests.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after registration of the medicinal product in order to ensure continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to periciazine, other phenothiazine derivatives or to any of the excipients of the drug;
• Closed-angle glaucoma;
• Urinary retention due to prostate diseases;
• History of agranulocytosis;
• History of porphyria;
• Concomitant therapy with dopamine receptor agonists (levodopa, amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, piribedil, pramipexole, quinagolide, ropinirole, except for their use in patients with Parkinson’s disease) (see section “Drug Interactions”);
• Vascular insufficiency (collapse);
• Acute poisoning with substances that depress the central nervous system, or coma;
• Heart failure;
• Pheochromocytoma;
• Severe pseudoparalytic myasthenia (Erb-Goldflam disease);
• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;
• Children under 3 years of age.

With caution

• In patients with predisposing factors for the development of ventricular arrhythmias (with cardiovascular diseases; congenital long QT interval; bradycardia; hypokalemia; receiving concomitant therapy with drugs that can prolong the QT interval and/or cause severe bradycardia less than 55 beats/min, slow intracardiac conduction, change the electrolyte composition of the blood);
• In patients with renal and/or hepatic insufficiency (risk of drug accumulation);
• In elderly patients;
• In patients with cardiovascular diseases (due to the risk of developing hypotensive and quinidine-like effects, as well as the ability of the drug to cause tachycardia);
• In elderly patients with dementia;
• In patients with risk factors for stroke;
• In patients with risk factors for venous thromboembolic complications;
• In patients with epilepsy;
• In patients with Parkinson’s disease;
• In patients with hyperthyroidism (increased risk of agranulocytosis when using periciazine in combination with drugs for the treatment of hyperthyroidism);
• In patients with changes in the peripheral blood picture (increased risk of developing leukopenia or agranulocytosis);
• In patients with breast cancer (possibility of disease progression due to increased blood prolactin concentration);
• In patients with diabetes mellitus and patients with risk factors for developing diabetes mellitus;
• In pediatric patients, especially under 6 years of age.

Use in Pregnancy and Lactation

Pregnancy

The use of the drug Neuleptil^® is not recommended during pregnancy and in women of childbearing potential not using contraception, except in cases where the expected benefit outweighs the potential risk to the fetus.

The available data obtained in animal studies are insufficient to confirm reproductive toxicity, while, according to animal studies, no teratogenic effect has been established.

The available data on the use of the drug Neuleptil^® in humans are insufficient to exclude the risk of congenital malformations in children exposed to the drug during intrauterine development.

If possible, at the end of pregnancy, preferably by reducing the dose, both neuroleptics and antiparkinsonian drugs that enhance their atropine-like action should be gradually discontinued.

In newborns, the state of the nervous system and gastrointestinal function should be monitored.

The following disorders have been reported in newborns whose mothers took neuroleptics from the group of phenothiazine derivatives in the third trimester of pregnancy (post-marketing data)

• Respiratory disorders of varying severity (from tachypnea to respiratory failure), bradycardia and decreased blood pressure, especially common if the mother was simultaneously taking other medications (such as psychotropic drugs and drugs with atropine-like effects);
• Symptoms associated with the atropine-like action of phenothiazine derivatives, such as meconium ileus, delayed meconium passage, feeding difficulties, abdominal distension, tachycardia;
• Neurological disorders, such as extrapyramidal disorders (including tremor and muscle hypertonia), drowsiness, agitation.

Medical supervision of children born to mothers taking the drug Neuleptil^® is recommended, and if necessary, appropriate treatment should be prescribed to them.

Breastfeeding period

Phenothiazine derivatives may be excreted in breast milk, so breastfeeding during treatment with the drug Neuleptil^® is not recommended.

Fertility

The available data obtained in animal studies are insufficient to assess the potential effect of periciazine on fertility.

Use in Hepatic Impairment

The drug should be used with caution in patients with hepatic insufficiency.

Use in Renal Impairment

The drug should be used with caution in patients with renal insufficiency.

Pediatric Use

The drug is contraindicated in children under 3 years of age.

Due to a possible relationship between the use of drugs of the phenothiazine derivative group and the development of sudden infant death syndrome (SIDS), Neuleptil^® is contraindicated in children under 1 year of age.

The use of the drug in children under 6 years of age is possible only in exceptional cases, under strict medical supervision and in specialized institutions. Neurological symptoms and signs should be monitored.

In case of using the drug in children, an annual clinical examination is recommended to assess the child’s learning ability, as the drug may cause a decrease in cognitive functions.

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

This dosage form (oral solution) is not recommended for patients with liver diseases, alcoholism, epilepsy, traumatic or drug-induced brain lesions, or pregnant women, because the oral solution contains ethanol.

Hypersensitivity reactions

Hypersensitivity reactions, including urticaria and angioedema, have been reported with the use of Neuleptil^®. In case of an allergic reaction, the use of Neuleptil^® should be discontinued and appropriate symptomatic treatment initiated.

Leukopenia, agranulocytosis

Since cases of leukopenia and agranulocytosis have been reported, monitoring with a complete blood count with differential is recommended. The occurrence of infections or fever of unknown origin may indicate blood dyscrasia and requires immediate performance of a complete blood count.

All patients should be informed that in case of fever, sore throat, or any other infection, they should immediately report it to their doctor and have a complete blood count performed. If significant changes (hyperleukocytosis, granulocytopenia) are observed in the blood test results, periciazine treatment should be discontinued.

Neuroleptic malignant syndrome

Treatment with Neuleptil^® should be discontinued in case of unexplained fever, which may be one of the symptoms of neuroleptic malignant syndrome, the early clinical manifestations of which may include pallor, hyperthermia, autonomic disturbances (pallor, tachycardia, unstable blood pressure, increased sweating, dyspnea), impaired consciousness, and muscle rigidity.

Signs of autonomic dysfunction, such as increased sweating and blood pressure instability, may precede the onset of hyperthermia and thus represent early symptoms of neuroleptic malignant syndrome. Although this effect of neuroleptics may be related to idiosyncrasy, there are predisposing factors for its occurrence, such as dehydration or organic brain lesions.

Ethanol (alcohol) consumption

Alcohol and ethanol-containing medications should not be taken during treatment, as the potentiation of the sedative effect leads to reduced reaction time, which can be dangerous for persons driving vehicles or operating machinery.

Patients with epilepsy

Due to the drug’s ability to lower the seizure threshold, patients with epilepsy treated with periciazine should be carefully monitored, and an EEG should be performed if possible. If seizures develop, the drug should be discontinued.

Patients with Parkinson’s disease

Except in special cases, Periciazine should not be used in patients with Parkinson’s disease (see sections “Contraindications” and “Drug Interactions”).

QT interval prolongation

Phenothiazine-derived neuroleptics can dose-dependently prolong the QT interval, which may increase the risk of severe ventricular arrhythmias, including life-threatening torsades de pointes, and sudden death. The risk of severe ventricular arrhythmias is increased in patients with bradycardia, hypokalemia, and QT interval prolongation (congenital or acquired due to drugs that prolong the QT interval). Before prescribing neuroleptics, if the patient’s condition allows, and during treatment with the drug, the presence of factors predisposing to these severe arrhythmias should be excluded (bradycardia less than 55 beats/min, hypokalemia, hypomagnesemia, slowed intraventricular conduction, and congenital long QT syndrome or QT prolongation with other QT-prolonging drugs). If the clinical situation allows, appropriate investigations (ECG monitoring and serum potassium levels, blood pressure monitoring) are recommended before and during treatment.

Intestinal obstruction

If abdominal distension and pain occur during periciazine administration, necessary examination should be performed to rule out paralytic ileus, as the development of this side effect requires emergency treatment.

Elderly patients

Neuleptil^® should be used with caution in elderly patients due to increased predisposition to orthostatic hypotension, sedative effects, extrapyramidal disorders, hyperthermia in hot and hypothermia in cold weather, chronic constipation (risk of paralytic ileus), and possible prostatic hyperplasia (due to drug accumulation resulting from reduced liver and kidney function).

Elderly patients have an increased risk of drug-induced parkinsonism, especially with long-term treatment.

Given the hypersensitivity to drugs affecting the CNS, it is recommended to prescribe the drug at lower initial doses for elderly patients.

Stroke

In randomized clinical trials comparing some atypical neuroleptics with placebo in elderly patients with dementia, a 3-fold increase in the risk of cerebrovascular complications was observed. The mechanism of this increased risk of cerebrovascular complications is unknown. An increase in this risk with other neuroleptics or in other patient groups cannot be excluded, therefore Periciazine should be prescribed with caution to patients with risk factors for stroke.

Elderly patients with dementia

In elderly patients with psychosis associated with dementia, treatment with antipsychotic drugs was associated with an increased risk of death. An analysis of 17 placebo-controlled trials (mean duration 10 weeks) showed that most patients receiving atypical antipsychotic drugs had a 1.6-1.7 times greater risk of death than patients receiving placebo. In a typical placebo-controlled clinical trial, the mortality rate at the end of the 10-week treatment course was 4.5% for patients receiving the active drug (neuroleptic) compared to 2.6% for patients receiving placebo. Although the causes of death in clinical trials with atypical antipsychotic drugs varied, most deaths were either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia). Observational studies have confirmed that, similar to treatment with atypical antipsychotics, treatment with typical neuroleptics may also increase mortality. The extent to which the increased mortality may be attributed to the antipsychotic drug rather than some patient characteristics is unclear.

Venous thromboembolic complications

Cases of venous thromboembolic complications, sometimes fatal, have been observed with the use of antipsychotic drugs. Therefore, Periciazine should be used with caution in patients with risk factors for venous thromboembolic complications.

Patients with diabetes mellitus or risk factors for its development

Hyperglycemia and impaired glucose tolerance have been reported in patients taking Periciazine. In patients with an established diagnosis of diabetes mellitus or with risk factors for its development starting treatment with Neuleptil^®, appropriate monitoring of blood glucose levels should be performed during treatment.

Tardive dyskinesia

Long-term treatment with any drug of the phenothiazine derivative group may lead to the development of tardive dyskinesia, especially in elderly patients and children.

Withdrawal syndrome

After abrupt discontinuation of high-dose neuroleptics, acute withdrawal symptoms have been rarely reported, including nausea, vomiting, headache, anxiety, agitation, dyskinesia, dystonia, thermoregulation disturbance, and insomnia. Relapse of the underlying disease may also occur. Extrapyramidal reactions have been reported. Therefore, gradual withdrawal of the drug is recommended. Withdrawal symptoms may occur after using the drug at any dose. Discontinuation of the drug should be carried out under careful medical supervision.

Photosensitivity

Due to the possibility of photosensitivity, patients receiving Periciazine should be advised to avoid direct sunlight.

Contact sensitization

Since in very rare cases, individuals frequently handling phenothiazines may develop skin contact sensitization to phenothiazines, direct contact of the drug with the skin should be avoided.

Use in pediatrics

The drug is contraindicated in children under 3 years of age.

Due to a possible relationship between the use of phenothiazine derivative drugs and the development of sudden infant death syndrome (SIDS), Neuleptil^® is contraindicated in children under 1 year of age.

Use of the drug in children under 6 years of age is possible only in exceptional cases, under strict medical supervision and in specialized institutions. Neurological symptoms and signs should be monitored.

In case of drug use in children, an annual clinical examination is recommended to assess the child’s learning ability, as the drug may cause cognitive impairment.

Excipients

Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicine.

The drug contains a small amount of ethanol (alcohol), less than 100 mg per 40 mg dose. The small amount of alcohol contained in Neuleptil^® will not have significant effects.

The drug contains glycerol. Glycerol may cause headache, stomach upset, and diarrhea.

Effect on ability to drive and operate machinery

Patients should be warned about the possible development of drowsiness, dizziness, and blurred vision, and advised to refrain from driving vehicles or operating machinery, especially at the beginning of treatment.

Overdose

Symptoms

Symptoms of phenothiazine overdose include CNS depression, progressing from drowsiness to coma with areflexia. Patients with initial or moderate intoxication may experience anxiety, confusion, lethargy, agitation, dysarthria, ataxia, stupor, mydriasis, excited or delirious state. Other manifestations of overdose include decreased blood pressure, ventricular tachycardia and arrhythmia, risk of QT interval prolongation, ECG changes, collapse, hypothermia, miosis, tremor, muscle twitching, spasm or rigidity, convulsions, dystonic movements, muscle hypotonia, difficulty swallowing, respiratory depression, apnea, cyanosis. These symptoms may be enhanced with concurrent use of other drugs or ethanol (alcohol). The development of anticholinergic syndrome, severe parkinsonism, and polyuria leading to dehydration is also possible.

Treatment

In case of Neuleptil^® overdose, all appropriate measures should be taken immediately.

Treatment should be symptomatic and carried out in a specialized unit where monitoring of respiratory and cardiovascular functions is possible and continued until the overdose effects are completely resolved.

If less than 6 hours have passed since drug ingestion, gastric lavage or aspiration of gastric contents should be performed. The use of emetics is contraindicated due to the risk of aspiration of vomit against the background of CNS depression and/or extrapyramidal disorders. Activated charcoal may be used. There is no specific antidote.

Treatment should be aimed at maintaining vital body functions.

In case of decreased blood pressure, the patient should be placed in a horizontal position with legs elevated. Intravenous fluid infusion is indicated. If fluid administration is insufficient to correct hypotension, norepinephrine, dopamine, or phenylephrine may be administered. Epinephrine administration is contraindicated.

Hypothermia may resolve spontaneously, except when body temperature drops to a level where cardiac arrhythmias may develop (i.e., to 29.4°C (84.9°F)).

After normalization of body temperature and correction of hemodynamic and metabolic disorders, ventricular or supraventricular tachyarrhythmias may not require antiarrhythmic drugs. If life-threatening arrhythmias persist, antiarrhythmic drugs may be required. The use of lidocaine and, if possible, long-acting antiarrhythmic drugs should be avoided.

In case of CNS and respiratory depression, transfer to mechanical ventilation and antibacterial therapy to prevent pulmonary infections may be required.

For severe dystonic reactions, intramuscular or intravenous administration of procyclidine (5-10 mg) or orphenadrine (20-40 mg) is indicated. Seizures can be controlled with intravenous diazepam.

For extrapyramidal disorders, anticholinergic antiparkinsonian agents are administered intramuscularly.

Drug Interactions

Contraindicated combinations

With dopamine receptor agonists (levodopa, amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, piribedil, pramipexole, quinagolide, ropinirole) in patients without Parkinson’s disease – mutual antagonism between dopamine receptor agonists and periciazine. Treatment of neuroleptic-induced extrapyramidal disorders with dopamine receptor agonists should not be performed (since Periciazine blocks dopamine receptors). If it is necessary to correct neuroleptic-induced extrapyramidal disorders, preference should be given to anticholinergic antiparkinsonian agents rather than levodopa, due to mutual antagonism between neuroleptics and dopaminergic agents.

Not recommended combinations

With dopamine receptor agonists (levodopa, amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, piribedil, pramipexole, quinagolide, ropinirole) in patients with Parkinson’s disease – mutual antagonism between dopamine receptor agonists and periciazine.

Dopamine receptor agonists may cause or exacerbate psychotic disorders. If patients with Parkinson’s disease receiving dopaminergic agonists require treatment with a neuroleptic, they should be withdrawn by gradually reducing the doses until complete discontinuation (sudden withdrawal of dopaminergic agonists may increase the risk of neuroleptic malignant syndrome). Patients with Parkinson’s disease who require treatment with periciazine along with dopamine receptor agonists should use the minimum effective doses of both drugs.

With ethanol (alcohol) – potentiation of the sedative effect caused by periciazine. Impaired concentration may be dangerous for persons driving vehicles or operating machinery. Consumption of alcoholic beverages and ethanol-containing medications simultaneously with periciazine should be avoided.

With amphetamine, clonidine, guanethidine – the effect of these drugs is reduced when used concomitantly with neuroleptics.

With sulpiride – increased risk of ventricular arrhythmias, in particular ventricular fibrillation and torsades de pointes, due to additive effects on electrophysiological parameters. An increased risk of arrhythmias is noted with the concomitant use of neuroleptics with drugs that prolong the QT interval (including some antiarrhythmics, antidepressants, and other neuroleptics), as well as with drugs causing electrolyte imbalance.

Combinations requiring caution

With drugs that can prolong the QT interval (class IA and III antiarrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, sertindole, tricyclic antidepressants, lithium salts, cisapride and others) – increased risk of arrhythmias.

With thiazide diuretics – the risk of arrhythmias increases, due to the possibility of electrolyte disorders (hypokalemia, hypomagnesemia).

With antihypertensive agents, especially alpha-blockers – enhancement of the hypotensive effect and risk of orthostatic hypotension (additive effect). For clonidine and guanethidine, see the “Drug Interactions” section, subsection “Not recommended combinations”.

With beta-blockers – risk of hypotension, especially orthostatic (additive effect), and risk of irreversible retinopathy, arrhythmias, and tardive dyskinesia.

With other drugs that have a depressant effect on the CNS: morphine derivatives (analgesics, antitussives), barbiturates, benzodiazepines, non-benzodiazepine anxiolytics, hypnotics, neuroleptics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H₁-histamine receptor blockers, centrally acting antihypertensive agents, baclofen, thalidomide, pizotifen – risk of additional depressant effect on the CNS, respiratory depression (which can be dangerous for persons driving vehicles or operating machinery).

With tricyclic antidepressants, MAO inhibitors, maprotiline – increased risk of neuroleptic malignant syndrome, possible enhancement and prolongation of sedative and anticholinergic effects. The administration of periciazine to patients who have taken MAO inhibitors within the preceding 14 days, as well as the administration of MAO inhibitors during periciazine use, should be avoided.

The necessity of concomitant administration of periciazine with drugs that lower the seizure threshold should be carefully evaluated due to the risk of seizures.

Metabolism involving the cytochrome P450 isoenzyme CYP2D6 – some phenothiazine derivative drugs are moderate inhibitors of the CYP2D6 isoenzyme. Pharmacokinetic interactions are possible between inhibitors of the CYP2D6 isoenzyme, such as phenothiazine derivatives, and substrates of the CYP2D6 isoenzyme. Concomitant use of periciazine with amitriptyline/amitriptylinoxide, a substrate of the CYP2D6 isoenzyme, may lead to an increase in the plasma concentration of amitriptyline/amitriptylinoxide. Patients should be monitored for the development of dose-dependent adverse reactions associated with amitriptyline/amitriptylinoxide use.

With atropine and other anticholinergics, as well as drugs with anticholinergic action (imipramine antidepressants, sedative H₁-histamine receptor blockers, anticholinergic antiparkinsonian drugs, atropine-like antispasmodics, disopyramide) – possibility of cumulative undesirable effects associated with anticholinergic action, such as urinary retention, constipation, dry mouth, heat stroke, etc., as well as a decrease in the antipsychotic effect of neuroleptics.

With hepatotoxic drugs – increased risk of hepatotoxic action.

With lithium salts (when using periciazine in high doses) – concurrent use may increase the risk of QT interval prolongation, as well as the risk of neuropsychiatric signs indicating the development of neuroleptic malignant syndrome or lithium intoxication. Regular clinical examination of the patient and monitoring of serum lithium concentration should be carried out, especially at the beginning of combined therapy.

With alpha- and beta-adrenomimetics (epinephrine, ephedrine) – reduction of their effects, paradoxical decrease in blood pressure is possible.

With antithyroid drugs – increased risk of agranulocytosis.

With apomorphine – reduction of the emetic effect of apomorphine, enhancement of its depressant effect on the central nervous system.

With hypoglycemic agents – concurrent use with neuroleptics may lead to an increase in blood glucose concentration. The patient should be informed about this and recommended to enhance self-monitoring of blood and urine glucose concentration. If necessary, the dose of hypoglycemic agents should be adjusted during and after discontinuation of neuroleptic treatment.

With antacids (salts, oxides and hydroxides of magnesium, aluminum and calcium) – reduced absorption of periciazine in the gastrointestinal tract. The interval between taking antacids and periciazine should be at least 2 hours.

With bromocriptine – increased plasma prolactin concentration when taking periciazine counteracts the effects of bromocriptine.

With appetite suppressants (except fenfluramine) – reduction of their effect.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date printed on the packaging.

The shelf life of the drug after first opening the bottle is 3 months.

After opening the bottle, the drug should be stored at a temperature below 25°C (77°F).

Dispensing Status

The drug is dispensed by prescription.

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.