Sulpiride-zn

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

Composition:

Active substance: sulpiride;

1 tablet contains 200 mg of sulpiride;

Excipients: celactose 80 (a mixture of monohydrate lactose and powdered cellulose (75:25)), microcrystalline cellulose, corn starch, colloidal anhydrous silicon dioxide, talc, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white tablets, round cylindrical in shape, with convex surfaces, beveled edges and a score line on one side.

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 has antipsychotic activity.

Pharmacokinetics.

After oral administration of a single 200 mg tablet, peak plasma concentration of sulpiride (0.73 mg/L) is reached within 3–6 hours.

The bioavailability of oral dosage forms is 25–35%, with wide individual variability; sulpiride exhibits a linear pharmacokinetic profile after administration in doses ranging from 50 to 300 mg.

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 is detected in breast milk in insignificant amounts and is able to cross the placental barrier.

Sulpiride is practically not metabolized in the human body.

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

Clinical characteristics.

Indications.

Acute mental disorders. Chronic mental disorders (schizophrenia, chronic delirium of non-schizophrenic nature: paranoid delusion, chronic hallucinatory psychosis).

Contraindications.

• Hypersensitivity to sulpiride or any of the excipients of the medicinal product (see section "Composition").
• Prolactin-dependent tumours (e.g., prolactin-secreting pituitary adenoma (prolactinoma) and breast cancer).
• Known or suspected diagnosis of phaeochromocytoma.
• Acute porphyria.
• Combinations with dopamine receptor agonists not used for the treatment of Parkinson's disease (cabergoline, quinagolide), citalopram and escitalopram, hydroxyzine, domperidone and piperazine (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Sedative agents

It should be remembered that many medicinal products or substances may exhibit additive inhibitory effects on the central nervous system and lead to reduced mental performance. 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, antihypertensive agents with central action, baclofen and thalidomide.

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

This serious cardiac arrhythmia may be caused by several medicinal products, with or without antiarrhythmic activity. Contributing factors include hypokalaemia (see "Combinations requiring caution (Potassium-sparing agents)") and bradycardia (see "Combinations requiring caution (Medicinal products causing bradycardia)") or the presence of congenital or acquired QT interval prolongation.

Such agents include, in particular, antiarrhythmic agents of class Ia and III and certain neuroleptics. This effect is also induced by other agents not belonging to these classes. Erythromycin, dolasetron, spiramycin and vinкамин induce such interactions only in intravenous formulations.

Concomitant administration of two "torsadogenic" (inducing torsades de pointes) medicinal products is generally contraindicated.

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

However, citalopram, domperidone and escitalopram are not among these exceptions: their use in combination with any medicinal product 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-Parkinson's disease 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).

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

Antiparasitic agents that may induce torsades de pointes (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 the two concomitantly used agents should be discontinued.

If concomitant treatment cannot be avoided, QT interval should be assessed by ECG before initiation of treatment and ECG monitoring should be performed during therapy.

Anti-Parkinson's 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. In patients with Parkinson's disease receiving dopamine agonist therapy, if neuroleptics are required, the dose of dopamine agonists should be gradually reduced until complete withdrawal (abrupt discontinuation may expose the patient to the risk of neuroleptic malignant syndrome).

Other medicinal products 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), and other agents such as arsenic compounds, difemanel, intravenous dolasetron, domperidone, intravenous erythromycin, hydroxychloroquine, levofloxacin, mequitazine, mizolastine, prucalopride, intravenous vinкамin, moxifloxacin, intravenous spiramycin, toremifene 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, tiaramide, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipothiazide, 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 neuroleptics.

Due to impaired concentration ability, driving vehicles and operating machinery may be hazardous.

Patients should avoid consumption of alcoholic beverages or use of 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.

Medicinal products causing bradycardia (e.g., class Ia antiarrhythmics, beta-blockers, certain class III antiarrhythmics, certain calcium channel blockers, crizotinib, digoxin glycosides, pasireotide, pilocarpine, anticholinesterase agents)

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).

Existing hypokalaemia should be corrected before administration, and clinical monitoring, electrolyte control and ECG monitoring are required.

Lithium

Risk of neuropsychiatric symptoms indicating neuroleptic malignant syndrome or lithium toxicity.

Clinical status and laboratory results should be monitored regularly, especially at the beginning of concomitant therapy. Discontinuation of one of the two agents is recommended at the first signs of neurotoxicity.

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.

Sucralfate

Reduced gastrointestinal absorption of sulpiride.

An interval of at least 2 hours (if possible) should be maintained between administration of sucralfate and sulpiride.

Locally acting gastrointestinal agents, antacids and activated charcoal

Reduced gastrointestinal absorption of sulpiride.

An interval of at least 2 hours (if possible) should be maintained between administration of these agents and sulpiride.

Combinations with precautions

Other sedative agents

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

Antihypertensive agents

Increased risk of arterial hypotension, particularly orthostatic.

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

See "Combinations requiring caution" for beta-blockers used in heart failure. 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 reduced efficacy of treatment when used concomitantly with orlistat.

Special precautions for use.

In patients with diabetes mellitus or risk factors for developing diabetes, blood glucose levels should be adequately monitored 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 dosage and intensified monitoring are recommended; in cases of severe renal impairment, intermittent treatment courses are advisable.

During sulpiride treatment, closer monitoring 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 more susceptible to postural hypotension, sedative effects, and extrapyramidal effects of the drug.

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

Potentially fatal neuroleptic malignant syndrome.

In case of unexplained fever, treatment should be discontinued immediately, as this may be one of the symptoms of a malignant syndrome that may develop during treatment with neuroleptics (pallor, hyperthermia, autonomic dysfunction, impaired consciousness, muscle rigidity).

Signs of autonomic dysfunction, such as excessive sweating and changes in blood pressure, may develop prior to hyperthermia and should therefore be considered as early warning symptoms.

Although this effect of neuroleptics may be idiosyncratic, 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 increases the risk of serious ventricular arrhythmias, particularly paroxysmal ventricular tachycardia of the torsades de pointes type, is more commonly observed in patients with bradycardia, hypokalemia, and congenital or acquired QT interval prolongation (especially when sulpiride is taken concomitantly with a medicinal product that causes QT prolongation) (see section "Adverse reactions").

Therefore, before initiating treatment and when clinically feasible, patients should be evaluated for risk factors for this type of arrhythmia: bradycardia less than 55 beats per minute, hypokalemia, congenital QT prolongation, or concomitant use of 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 during 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 mechanism of this increased risk is unknown. An increased risk with the use of other antipsychotics or in other patient populations cannot be ruled out. This medicinal product should be prescribed with caution to patients who have risk factors for stroke.

Elderly patients with dementia.

The risk of fatal outcome 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 generally taking atypical antipsychotics showed that the risk of fatal outcome was increased by 1.6–1.7 times in patients taking these drugs compared to placebo.

After completion of the average treatment period of 10 weeks, the risk of fatal outcome was 4.5% in the treatment group compared to 2.6% in the placebo group.

Although the causes of fatal outcomes in clinical trials with atypical antipsychotics varied, most deaths were due to cardiovascular (e.g., heart failure, sudden death) or infectious conditions (e.g., pneumonia).

Epidemiological studies suggest that treatment with conventional antipsychotics may increase mortality to a similar extent as atypical antipsychotics.

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

Venous thromboembolism (VTE).

Cases of venous thromboembolism (VTE), sometimes fatal, have been reported during treatment with antipsychotics. Since patients taking antipsychotics often have acquired risk factors for VTE, all potential risk factors for VTE should be identified before and during treatment with Sulpiride-ZN, 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 intestinal 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. 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 cause torsades de pointes is not recommended (see section "Adverse reactions").

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 benign prostatic hyperplasia.

Sulpiride should be used with caution in patients with hypertension, particularly elderly patients, due to the risk of hypertensive crisis. Careful monitoring of the patient's condition is required.

This medicinal product contains lactose. If the patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy.

In animal studies, reduced fertility related to the pharmacological properties of the drug (prolactin-mediated effect) was observed. Results of animal studies do not indicate a direct or indirect harmful effect on pregnancy, embryonic/fetal development, or postnatal development. Data on the effects of sulpiride during human pregnancy are very limited. 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 limited experience with sulpiride use during pregnancy, its use is not recommended. Neonates whose mothers received antipsychotics (including Sulpiride-ZN) 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.

Period of breastfeeding.

Since sulpiride is excreted in breast milk, breastfeeding during treatment is not recommended.

Ability to affect reaction speed while driving or operating machinery.

Patients, especially those who drive vehicles or operate machinery, should be warned that use of this medicinal product may cause somnolence (see section "Adverse reactions"). Driving vehicles or operating machinery is contraindicated during treatment with this medicinal product.

Method of Administration and Dosage.

For oral use.

The minimum effective dose should always be prescribed.

If the patient's clinical condition allows, treatment should be initiated with a low dose, followed by gradual dose titration.

This medicinal formulation is intended for use in adults only.

The daily dose is 200–1000 mg.

Children.

This medicinal formulation is intended for use in adults only.

Overdose.

Experience regarding sulpiride overdose is limited. Dyskinetic symptoms 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 mainly following administration of sulpiride in combination with other psychotropic substances.

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

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

Adverse Reactions

Blood and lymphatic system disorders.

Uncommon: leukopenia.

Frequency unknown: neutropenia, agranulocytosis.

Immune system disorders.

Frequency unknown: anaphylactic reactions: urticaria, dyspnea, hypotension, anaphylactic shock.

Endocrine disorders.

Common: hyperprolactinemia.

Psychiatric disorders.

Common: insomnia.

Frequency unknown: confusion.

Nervous system disorders.

Common: sedative effect or drowsiness; extrapyramidal syndrome, which shows partial response to anticholinergic antiparkinsonian agents; parkinsonism, tremor; hyperkinetic-hypertonic, agitated motor activity; akathisia.

Uncommon: hypertonia, dyskinesia, dystonia.

Rare: oculogyric crisis.

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

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

Metabolism and nutrition disorders.

Frequency unknown: hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

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, postpartum and perinatal period.

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

Reproductive system and breast disorders.

Common: galactorrhea.

Uncommon: amenorrhea, impotence or frigidity.

Frequency unknown: gynecomastia.

General disorders.

Common: weight gain.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals should 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 of children.

Packaging.

10 tablets in a blister; 1 or 2 blisters per carton.

Prescription category.

Prescription only.

Manufacturer.

Limited liability company "Kharkiv Pharmaceutical Enterprise "Zdorovia Narodu".

Manufacturer's location and address of business activity.

Ukraine, 61002, Kharkiv region, city of Kharkiv, Kuilivska Street, building 41.