SULPIRIDE -ZN

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SULPIRID-ZN (SULPIRID-ZN)

Composition:

Active substance: sulpiride;

1 ml of solution contains 50 mg of sulpiride;

Excipients: sodium chloride, sulfuric acid, water for injections.

Pharmaceutical form. Injection solution.

Main physico-chemical properties: clear, colorless or almost colorless liquid, odorless or with a faint specific odor.

Pharmacotherapeutic group. Antipsychotic agents. ATC code N05A L01.

Pharmacological properties.

Pharmacodynamics.

Sulpiride affects dopaminergic neurotransmission in the brain as a dopamine agonist, thereby exerting an activating effect at low doses. At higher doses, sulpiride also exerts anti-reproductive effects.

Pharmacokinetics.

After intramuscular administration of a 100 mg dose, peak plasma concentration of sulpiride is reached within 30 minutes and amounts to 2.2 mg/L.

Sulpiride rapidly distributes into body tissues: the apparent volume of distribution at steady state is 0.94 L/kg. Plasma protein binding is 40%.

Sulpiride appears in negligible amounts in breast milk and is able to cross the placental barrier. Sulpiride is practically not metabolized in the human body; 92% of the administered dose of sulpiride administered via intramuscular injection is excreted unchanged in urine.

It is primarily excreted by the kidneys via glomerular filtration. Renal clearance is 126 mL/min. The elimination half-life from plasma is 7 hours.

Clinical characteristics.

Indications.

Sulpiride-ZN is indicated for the short-term treatment of agitation and aggression in patients with acute and chronic psychiatric disorders (schizophrenia, chronic delirium of non-schizophrenic origin: paranoid delusion, chronic hallucinatory psychosis).

Contraindications.

Sulpiride-ZN is contraindicated in the following cases:

• Hypersensitivity to sulpiride or any of the excipients of the medicinal product (see section "Composition");
• Prolactin-dependent tumors (e.g., prolactin-secreting pituitary adenoma (prolactinoma) and breast cancer);
• Known or suspected diagnosis of pheochromocytoma;
• Acute porphyria;
• Combinations with non-antiparkinsonian dopamine agonists (cabergoline, quinagolide), citalopram and escitalopram, hydroxyzine, domperidone, and piperazine (see section "Interaction with other medicinal products and other forms of interaction").

The medicinal product in this pharmaceutical form is intended only for adult patients.

Interaction with other medicinal products and other forms of interaction.

Sedatives

It should be remembered that many medicinal products may exhibit additive central nervous system depressant effects and lead to reduced mental alertness. These include morphine derivatives (analgesics, antitussives, and substitution therapy agents), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally acting antihypertensives, baclofen, and thalidomide.

Medicinal products that may induce torsades de pointes (paroxysmal ventricular tachycardia)

This serious cardiac arrhythmia may be caused by certain medicinal products, both with and without antiarrhythmic activity. Precipitating factors include hypokalemia (see "Potassium-sparing agents") and bradycardia (see "Agents causing bradycardia"), or the presence of congenital or acquired QT interval prolongation.

Such agents include, in particular, antiarrhythmic agents of classes Ia and III, and some neuroleptics. This effect may also be induced by other agents not belonging to these classes.

Dolasetron, erythromycin, spiramycin, and vinca alkaloids only in intravenous formulations may interact in this way.

Concomitant administration of two "torsadogenic" (those causing torsades de pointes) agents is generally contraindicated.

However, some of these agents are exceptions, as their use cannot be avoided. Therefore, they are simply not recommended for use in combination with medicinal products that may induce torsades de pointes. This applies to methadone, antiparasitic agents (chloroquine, halofantrine, lumefantrine, pentamidine), and neuroleptics.

However, citalopram, domperidone, and escitalopram are not among these exceptions: their concomitant use with all medicinal products that may induce torsades de pointes is contraindicated.

Contraindicated combinations (see section "Contraindications").

Citalopram, escitalopram

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Non-antiparkinsonian dopamine receptor agonists (cabergoline, quinagolide)

Mutual antagonism exists between dopamine agonists and neuroleptics.

Domperidone

Increased risk of ventricular arrhythmia, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Hydroxyzine

Increased risk of ventricular arrhythmia, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Piperazine

Increased risk of ventricular arrhythmia, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Unwanted combinations (see section "Special precautions for use").

Antiparasitic agents that may induce torsades de pointes (paroxysmal ventricular tachycardia) (chloroquine, halofantrine, lumefantrine, pentamidine)

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). If possible, one of these agents should be discontinued.

If concomitant treatment cannot be avoided, QT interval should be assessed by ECG prior to treatment initiation and ECG monitoring should be performed during treatment.

Antiparkinsonian dopamine agonists (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, rasagiline, rotigotine, selegiline)

Mutual antagonism exists between dopamine agonists and neuroleptics.

Dopamine agonists may induce or exacerbate psychiatric disorders. If neuroleptics are required in patients with Parkinson's disease who are receiving dopamine agonist therapy, dopamine agonist doses should be gradually reduced until complete discontinuation (abrupt withdrawal may predispose the patient to malignant neuroleptic syndrome).

Other agents that may induce torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type) (Class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide) and Class III (amiodarone, dronedarone, sotalol, dofetilide, ibutilide), other agents such as arsenic compounds, diphenylhydantoin, intravenous dolasetron, intravenous erythromycin, hydroxychloroquine, levofloxacin, mizolastine, prucalopride, intravenous vinca alkaloids, moxifloxacin, intravenous spiramycin, torasemide, and vandetanib)

High risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Other neuroleptics that may induce torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type) ( amisulpride, chlorpromazine, thiethylazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipotiazide, sulpiride, tiapride, zuclopenthixol)

High risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Alcohol (beverage or excipient)

Potentiation of sedative effects of neuroleptic agents.

Due to impaired concentration ability, driving and operating machinery may be hazardous. Patients should avoid consuming alcoholic beverages or taking medicinal products containing alcohol.

Levodopa

Mutual antagonism exists between levodopa and neuroleptics.

Patients with Parkinson's disease receiving treatment with dopamine agonists and neuroleptics should be prescribed the minimum effective doses of both agents.

Methadone

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Combinations requiring caution.

Anagrelide

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). ECG monitoring and clinical surveillance are required during concomitant use.

Azithromycin

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). ECG monitoring and clinical surveillance are required during concomitant use.

Beta-blockers used in patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). Clinical monitoring and ECG control are required.

Agents causing bradycardia (e.g., Class Ia antiarrhythmics, beta-blockers, certain Class III antiarrhythmics, certain calcium channel blockers, crizotinib, digoxin glycosides, pasireotide, pilocarpine, cholinesterase inhibitors)

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). Clinical monitoring and ECG control are required.

Ciprofloxacin, levofloxacin, norfloxacin

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). ECG monitoring and clinical surveillance are required during concomitant use.

Clarithromycin

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). ECG monitoring and clinical surveillance are required during concomitant use.

Potassium-sparing agents (potassium-sparing diuretics, alone or in combination, stimulant laxatives, glucocorticoids, tetracosactide, and intravenous amphotericin B)

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type).

Correct existing hypokalemia before administration. Clinical monitoring, electrolyte control, and ECG monitoring are required.

Lithium

Risk of neuropsychiatric symptoms indicating malignant neuroleptic syndrome or lithium toxicity. Clinical status and laboratory results should be monitored regularly, especially at the beginning of concomitant therapy. If early signs of neurotoxicity appear, discontinuation of one of the two agents is recommended.

Ondansetron

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). ECG monitoring and clinical surveillance are required during concomitant use.

Roxithromycin

Increased risk of ventricular arrhythmias, particularly torsades de pointes (paroxysmal ventricular tachycardia of the "twisting of points" type). ECG monitoring and clinical surveillance are required during concomitant use.

Combinations requiring precautions.

Other sedatives

More pronounced central nervous system depression. Due to impaired concentration ability, driving and operating machinery may be hazardous.

Antihypertensive agents

Increased risk of arterial hypotension, particularly orthostatic hypotension.

Beta-blockers used in patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)

For beta-blockers used in heart failure, see "Combinations requiring caution." Vasodilatory effect and risk of hypotension, particularly postural (additive effect).

Dapoxetine

Risk of increased frequency of adverse effects, particularly dizziness or syncope.

Orlistat

Risk of treatment inefficacy when used concomitantly with orlistat.

Special precautions for use.

In patients with diabetes mellitus or those with risk factors for developing diabetes, appropriate monitoring of blood glucose levels should be performed at the beginning of sulpiride therapy.

Except in special cases, this medicinal product should not be prescribed to patients with Parkinson's disease.

For patients with renal impairment, reduced doses and intensified monitoring are recommended; in cases of severe renal insufficiency, intermittent treatment courses are advisable.

More careful monitoring during sulpiride treatment is required for:

• Patients with epilepsy, as sulpiride may lower the seizure threshold; cases of seizures have been reported in patients treated with sulpiride (see section "Adverse reactions");
• Elderly patients, who are prone to postural hypotension and are more susceptible to sedative and extrapyramidal effects of the drug.

Leucopenia, neutropenia, and agranulocytosis have been reported during treatment with antipsychotics, including sulpiride. Unexplained infections or fever of unknown etiology may be signs of leucopenia (see section "Adverse reactions"); in such cases, a blood count should be performed immediately.

Potentially fatal neuroleptic malignant syndrome.

If fever of unknown etiology occurs, treatment must be discontinued immediately, as this may be one of the symptoms of a malignant syndrome that may develop during treatment with neuroleptic agents (pallor, hyperthermia, autonomic dysfunction, impaired consciousness, muscle rigidity).

Signs of autonomic dysfunction, such as excessive sweating and blood pressure changes, may precede hyperthermia and represent early warning symptoms. Although this effect of neuroleptic agents may be idiopathic in nature, risk factors such as dehydration and organic brain damage may be present.

QT interval prolongation.

Sulpiride may cause dose-dependent QT interval prolongation. This effect, which is known to increase the risk of serious ventricular arrhythmias, particularly torsades de pointes, is more frequently observed in patients with bradycardia, hypokalemia, and congenital or acquired QT prolongation (when sulpiride is taken concomitantly with a medicinal product that causes QT prolongation) (see section "Adverse reactions").

Therefore, before initiating treatment with this medicinal product, if clinically feasible, the presence of risk factors for this type of arrhythmia should be assessed: bradycardia less than 55 beats per minute, hypokalemia, congenital QT prolongation, concomitant treatment with a medicinal product that may cause marked bradycardia (less than 55 beats per minute), hypokalemia, slowed intracardiac conduction, or QT interval prolongation (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").

Except in emergency situations, it is recommended to perform an ECG at the initial evaluation of patients who are to receive neuroleptic treatment.

Stroke.

In randomized, placebo-controlled clinical trials in elderly patients with dementia treated with certain atypical antipsychotics, an increased risk of stroke was observed compared to those receiving placebo. The reason for this increased risk is unknown. An increased risk with the use of other antipsychotics or in other patient populations cannot be excluded. This medicinal product should be prescribed with caution to patients who have risk factors for stroke.

Elderly patients with dementia.

The risk of mortality is increased in elderly patients with psychosis associated with dementia who are treated with antipsychotics.

An analysis of data from 17 placebo-controlled trials (with a mean duration of 10 weeks) involving patients taking atypical antipsychotics showed that the risk of mortality was increased by 1.6–1.7 times in patients receiving these drugs compared to those receiving placebo.

After an average treatment duration of 10 weeks, the mortality risk was 4.5% in the treatment group compared to 2.6% in the placebo group.

Although the causes of death in clinical trials with atypical antipsychotics were varied, most fatalities resulted from cardiovascular (e.g., heart failure, sudden death) or infectious diseases (e.g., pneumonia).

Epidemiological studies suggest that treatment with conventional antipsychotics may also increase mortality, similar to atypical antipsychotics.

The relative contribution of the antipsychotic agent and individual patient characteristics to the increased mortality rate in epidemiological studies remains unclear.

Venous thromboembolism (VTE).

Venous thromboembolic events (VTE) have been reported occasionally during treatment with antipsychotics. Since patients receiving antipsychotics often have acquired risk factors for VTE, all potential risk factors for VTE should be identified before and during treatment, and preventive measures should be taken (see section "Adverse reactions").

Breast cancer.

Since sulpiride may increase prolactin levels, it should be used with caution. All patients, regardless of gender, with a personal or family history of breast cancer require careful monitoring during sulpiride treatment.

Reduced intestinal motility.

Cases of intestinal obstruction have been reported in patients receiving antipsychotics. Rare cases of ischemic colitis and intestinal necrosis, sometimes fatal, have also been reported. Most patients were concurrently receiving one or more medicinal products that reduce gastrointestinal motility (particularly those with anticholinergic properties). Particular attention should be paid to symptoms such as abdominal pain with vomiting and/or diarrhea. Constipation should be promptly recognized and actively treated. The development of paralytic or mechanical intestinal obstruction requires immediate medical intervention.

Concomitant use of this medicinal product with alcohol, levodopa, dopamine receptor agonists, antiparasitic agents that may cause torsades de pointes, methadone, other neuroleptics, and medicinal products that may induce torsades de pointes is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Sulpiride has anticholinergic effects; therefore, it should be used with caution in patients with glaucoma, intestinal obstruction, congenital stenosis of the gastrointestinal tract, urinary retention, or a history of prostate hyperplasia.

Sulpiride should be used with caution in patients predisposed to hypertension, particularly elderly patients, due to the risk of hypertensive crisis. Therefore, appropriate monitoring of such patients is required.

Excipients.

This medicinal product contains 30 mg of sodium per 800 mg sulpiride dose. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy.

In animal studies, reduced fertility related to the pharmacological properties of the drug (prolactin-mediated effect) has been observed. Results from animal studies do not indicate a direct or indirect harmful effect on pregnancy, embryonic/fetal development, and/or postnatal development. Very limited human data are available regarding the effects on pregnancy. In nearly all reported cases of fetal or neonatal developmental abnormalities associated with sulpiride use during pregnancy, alternative explanations appear more plausible. Therefore, due to the limited experience with sulpiride use during pregnancy, its use is not recommended. Neonates whose mothers received antipsychotics during the third trimester of pregnancy are at risk of developing adverse effects after birth, including extrapyramidal symptoms and/or withdrawal symptoms, with varying severity and duration. Reported adverse reactions include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory disorders, and feeding difficulties. Therefore, neonates should be closely monitored.

Breastfeeding period.

Since sulpiride passes into breast milk, breastfeeding during treatment is not recommended.

Ability to influence reaction speed when driving or operating machinery.

Patients, especially those who drive vehicles or operate machinery, should be warned that using this medicinal product may cause drowsiness (see section "Adverse reactions"). Driving vehicles and operating machinery are contraindicated during treatment with this drug.

Method of Administration and Dosage.

Administer the medicinal product intramuscularly.

Intended only for adult patients.

Always prescribe the lowest effective dose. If the patient's clinical condition allows, treatment should be initiated with a low dose (100 mg), followed by gradual dose titration as needed.

The dose is 400 to 800 mg per day for 2 weeks.

After opening the ampoule, the medicinal product must be used immediately.

Children.

This medicinal product formulation is intended only for adult patients.

Overdose.

Experience regarding sulpiride overdose is limited. Dystonic reactions may occur, including spasmodic torticollis, tongue protrusion, and trismus. In some patients, life-threatening parkinsonism or even coma may develop.

Fatal cases have been reported primarily following administration of sulpiride in combination with other psychotropic substances.

Sulpiride is partially removed by hemodialysis. There is no specific antidote for sulpiride.

Treatment should be symptomatic. Resuscitation with careful monitoring of cardiac function and respiration (risk of QT interval prolongation and ventricular arrhythmias) must be continued until full recovery of the patient. In case of severe extrapyramidal symptoms, anticholinergic agents should be administered.

Adverse Reactions

Blood and lymphatic system disorders

Uncommon: leucopenia.

Frequency unknown: neutropenia, agranulocytosis.

Immune system disorders

Frequency unknown: anaphylactic reactions: urticaria, anaphylactic shock.

Endocrine system disorders

Common: hyperprolactinaemia.

Psychiatric disorders

Common: insomnia.

Frequency unknown: confusion.

Nervous system disorders

Common: sedative effect or drowsiness; extrapyramidal syndrome, which shows partial response to anticholinergic antiparkinsonian drugs; parkinsonism, tremor, akathisia.

Uncommon: hypertonia, dyskinesia, dystonia.

Rare: oculogyric crisis.

Frequency unknown: potentially fatal neuroleptic malignant syndrome (see section "Special precautions for use"); hypokinesia.

Tardive dyskinesia, which may occur during prolonged treatment with all neuroleptics; in this case, anticholinergic antiparkinsonian drugs are ineffective and may worsen clinical manifestations.

Seizures (see section "Special precautions for use").

Metabolism and nutrition disorders

Frequency unknown: hyponatraemia, inadequate secretion of antidiuretic hormone.

Cardiac disorders

Rare: ventricular arrhythmias, including paroxysmal torsades de pointes and ventricular tachycardia, which may lead to ventricular fibrillation or cardiac arrest.

Frequency unknown: QT interval prolongation, sudden fatal outcome (see section "Special precautions for use").

Vascular disorders

Uncommon: orthostatic hypotension.

Frequency unknown: venous thromboembolism, pulmonary artery embolism, deep vein thrombosis (see section "Special precautions for use"), increased blood pressure (see section "Special precautions for use").

Respiratory, thoracic and mediastinal disorders

Frequency unknown: aspiration pneumonia (mainly when sulpiride is used concomitantly with other central nervous system depressants).

Gastrointestinal disorders

Common: constipation.

Uncommon: hypersalivation.

Hepatobiliary disorders

Common: increased liver enzyme activity.

Frequency unknown: cholestatic or mixed hepatitis.

Skin and subcutaneous tissue disorders

Common: maculopapular rash.

Pregnancy, puerperium and perinatal period

Frequency unknown: withdrawal syndrome in newborns (see section "Use during pregnancy or breastfeeding").

Reproductive system and breast disorders

Common: galactorrhoea.

Uncommon: amenorrhoea, impotence or frigidity.

Frequency unknown: gynaecomastia.

General disorders and administration site conditions

Common: weight gain.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals are required to report any adverse reactions via the adverse reaction reporting system in Ukraine.

Shelf life. 3 years.

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

Keep out of reach and sight of children.

Packaging.

2 ml in an ampoule; 10 ampoules per box.

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

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

Prescription status. Prescription only.

Manufacturer. Limited Liability Company "Kharkiv Pharmaceutical Enterprise "People's Health".

LIMITED LIABILITY COMPANY "CORPORATION "HEALTH".

Manufacturer's address and location of business activity.

Ukraine, 61002, Kharkiv region, city of Kharkiv, Kuikivska Street, 41.

(Limited Liability Company "Kharkiv Pharmaceutical Enterprise "People's Health")

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

(LIMITED LIABILITY COMPANY "CORPORATION "HEALTH")