Eglonil®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EGLONYL® (EGLONYL®)

Composition:

Active substance: sulpiride;

1 capsule contains 50 mg of sulpiride;

Excipients: lactose monohydrate, methylcellulose, talc, magnesium stearate, capsule shell: gelatin, titanium dioxide (E 171).

Pharmaceutical form. Capsules.

Main physicochemical properties: opaque white or almost white size 4 capsules containing a cream-white powder.

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 reduces productive symptomatology.

Pharmacokinetics.

After oral administration of a single 50 mg capsule, peak plasma concentration of sulpiride (0.25 mg/L) is reached within 3–6 hours.

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

Sulpiride is rapidly distributed 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 small amounts and may cross the placental barrier.

Sulpiride is practically not metabolized in the human body.

Sulpiride is mainly excreted by the kidneys via glomerular filtration. Its renal clearance is 126 mL/min. The elimination half-life from plasma is 7 hours.

Clinical characteristics.

Indications. Short-term symptomatic treatment of anxiety disorders in adults when standard therapeutic measures have not been effective.

Severe behavioural disorders (agitation, self-injury, stereotypy) in children aged 6 years and older, particularly in patients with autistic syndromes.

Contraindications.

• Hypersensitivity to sulpiride or to 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, pergolide), 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 have additive CNS depressant effects and may lead to reduced mental alertness. These include morphine derivatives (analgesics, antitussives and replacement therapy), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, antihypertensives 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 a number of medicinal products, both with and without antiarrhythmic activity. Precipitating factors include hypokalaemia (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 drugs of class Ia and III, and some neuroleptics. This effect may also be induced by other medicinal products not belonging to these classes.

This interaction involves dolasetron, erythromycin, spiramycin and vinpocetine only in intravenous formulations.

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

However, some of these medicinal products are exceptions, as their use cannot be avoided. Therefore, they are 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 any medicinal product that may induce torsades de pointes is contraindicated.

Contraindicated combinations (see section "Contraindications").

Citalopram, escitalopram

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

Non-Parkinsonian dopamine receptor agonists (cabergoline, pergolide)

There is mutual antagonism between dopamine agonists and neuroleptics.

Domperidone

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

Hydroxyzine

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

Piperaquine

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

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

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

Increased risk of ventricular arrhythmias, particularly paroxysmal ventricular tachycardia of the "torsades de pointes" type. If possible, one of these two medicinal products should be discontinued.

If concomitant use cannot be avoided, QT interval should be checked before initiation and ECG monitoring should be performed during treatment.

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

There is mutual antagonism between dopamine agonists and neuroleptics.

Dopamine agonists may induce or exacerbate psychiatric disorders. In patients with Parkinson's disease receiving treatment with dopamine agonists, if neuroleptics are required, the doses of dopamine agonists should be gradually reduced (abrupt withdrawal may expose the patient to the risk of neuroleptic malignant syndrome).

Other medicinal products that may induce torsades de pointes (paroxysmal ventricular tachycardia) (class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, dronedarone, sotalol, dofetilide, ibutilide) and other agents such as arsenic compounds, difemethiazine, intravenous dolasetron, domperidone, intravenous erythromycin, hydroxychloroquine, levofloxacin, mequitazine, mizolastine, prucalopride, intravenous vinpocetine, moxifloxacin, intravenous spiramycin, torasemide and vandetanib).

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

Other neuroleptics that may induce torsades de pointes (paroxysmal ventricular tachycardia) (amisulpride, chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipotiazide, sulpiride, tiapride, zuclopenthixol)

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

Combinations requiring caution

Anagrelide

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

Azithromycin

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

Agents causing bradycardia (e.g. class Ia antiarrhythmics, beta-blockers, some class III antiarrhythmics, some calcium channel blockers, crizotinib, digitalis glycosides, pasireotide, pilocarpine, anticholinesterase agents)

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

Cyprofl oxacin, levofloxacin, norfloxacin

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

Clarithromycin

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

Correction of existing hypokalaemia should be performed before administration, and clinical monitoring and control of electrolytes and ECG are required.

Lithium

Risk of neuropsychiatric changes suggestive of neuroleptic malignant syndrome or lithium toxicity. Regular clinical monitoring and laboratory tests are indicated, especially at the beginning of concomitant use. If early signs of neurotoxicity appear, one of the two medicinal products should be discontinued.

Ondansetron

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

Roxithromycin

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

Sucralfate

Reduced gastrointestinal absorption of sulpiride.

A time interval should be maintained between administration of sucralfate and sulpiride (more than 2 hours, if possible).

Locally acting gastrointestinal agents, antacids and activated charcoal

Reduced gastrointestinal absorption of sulpiride.

A time interval should be maintained between administration of these agents and sulpiride (more than 2 hours, if possible).

Combinations to be considered

Other sedative agents

More pronounced depression of central nervous system function. 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 reduced efficacy of treatment 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 dosage and intensified monitoring are recommended; in cases of severe renal impairment, intermittent treatment courses are advisable.

Careful monitoring is required during sulpiride treatment 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.

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

Potentially fatal neuroleptic malignant syndrome. Neuroleptic malignant syndrome — a potentially fatal complication reported during antipsychotic therapy — is characterized by hyperthermia, pallor, autonomic nervous system disturbances, altered consciousness, muscle rigidity, rhabdomyolysis, elevated serum creatine phosphokinase levels, and autonomic instability. Cases with atypical features, such as fever without muscle rigidity or hypertonia, have also been observed. In case of unexplained fever, which may be considered an early sign/symptom of neuroleptic malignant syndrome or atypical neuroleptic malignant syndrome, therapy with sulpiride and all other neuroleptics should be immediately discontinued under medical supervision.

Signs of autonomic nervous system dysfunction, such as excessive sweating and blood pressure changes, may precede 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 is known to increase the risk of serious ventricular arrhythmias, particularly paroxysmal ventricular tachycardia of the torsades de pointes type, is more frequently observed in patients with bradycardia, hypokalemia, and congenital or acquired QT interval prolongation (when sulpiride is taken concomitantly with a medicinal product that causes QT interval prolongation) (see section "Adverse reactions").

Therefore, before initiating treatment and whenever clinically feasible, the presence of patient risk factors predisposing to this type of arrhythmia should be assessed: bradycardia less than 55 beats per minute, hypokalemia, congenital QT interval 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 examination during the initial assessment of patients who are to receive neuroleptic treatment.

Stroke

During randomized, placebo-controlled clinical trials in elderly patients with dementia treated with certain atypical antipsychotics, an increased risk of stroke was observed. 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 death is increased in elderly patients with psychosis associated with dementia who are treated with antipsychotic agents.

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 death was 1.6–1.7 times higher in patients receiving these drugs compared to placebo.

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

Although the causes of death during clinical trials with atypical antipsychotics were varied, most deaths occurred due to either cardiovascular (e.g., heart failure, sudden death) or infectious diseases (e.g., pneumonia).

Observational 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 observational studies remains unclear.

Venous thromboembolism. Cases of venous thromboembolism (VTE) have been reported during the use of antipsychotic agents. 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 Eglonil® and preventive measures taken (see section "Adverse reactions").

Breast cancer. Sulpiride may increase prolactin levels. Therefore, it should be used with caution. Regardless of sex, patients with a personal or family history of breast cancer require careful monitoring during sulpiride therapy.

Reduced intestinal motility. Cases of intestinal obstruction have been reported in patients receiving antipsychotic agents. Rare cases of ischemic colitis and intestinal necrosis, sometimes fatal, have also been reported. Most of these patients were receiving concomitant treatment with one or more medicinal products that reduce gastrointestinal motility (particularly agents with anticholinergic properties). Particular attention should be paid to the onset of abdominal pain with vomiting and/or diarrhea. Early recognition and active treatment of constipation are very important. Development of paralytic or mechanical intestinal obstruction requires immediate treatment.

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 should be avoided (see section "Adverse reactions").

Even when used at low doses, the risk of developing tardive dyskinesia should be considered, particularly in elderly patients.

Since the efficacy and safety of sulpiride in children have not been fully established, appropriate precautions should be taken when using this agent (see section "Dosage and administration"). Due to the drug's effect on cognitive function, annual clinical assessments to evaluate learning ability are recommended. The dosage should be periodically adjusted according to the child's clinical status. The use of tablets and hard capsules is contraindicated in children under 6 years of age due to the risk of airway obstruction.

Eglonil® should be used with caution in patients with glaucoma, intestinal obstruction, congenital gastrointestinal stenosis, urinary retention, or a history of prostate hyperplasia.

Eglonil® should be used cautiously in patients with arterial hypertension, particularly elderly patients, due to the risk of hypertensive crisis. Close monitoring of the patient's condition is required.

This medicinal product contains lactose and therefore should not be used in patients with galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome (rare hereditary conditions).

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. The available data on sulpiride use during pregnancy are very limited. The safety of sulpiride during pregnancy has not been established. Sulpiride crosses the placental barrier. Animal studies have shown reproductive toxicity. Sulpiride is not recommended during pregnancy and in women of childbearing potential who are not using effective contraception, except when the expected benefits of treatment outweigh the potential risks. Neonates whose mothers received antipsychotics (including Eglonil®) 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. Adverse reactions reported include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory disorders, and feeding difficulties. Therefore, newborns should be carefully monitored.

Lactation. Sulpiride is excreted in breast milk in relatively large amounts. In some cases, the concentration exceeds 10% of the dose adjusted for maternal body weight. However, the concentration in infant blood has not been determined. There is insufficient data on the effects of sulpiride on neonates and infants.

The decision to discontinue breastfeeding or to discontinue sulpiride therapy should be made considering the benefits of breastfeeding for the infant and the benefits of continuing treatment for the mother.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration

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.

Adults. Short-term symptomatic treatment of anxiety states when standard therapeutic measures have been ineffective: the daily dose is 50–150 mg for not more than 4 weeks.

Children aged 6 years and older. Severe behavioral disorders (agitation, self-mutilation, stereotypy) in children aged 6 years and older, particularly in patients with autistic syndromes:

5–10 mg/kg body weight per day.

Children. The use of hard capsules is contraindicated in children under 6 years of age.

Overdose.

Experience with 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 mainly reported following concomitant use with other psychotropic drugs.

Sulpiride is partially removed 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) must be continued until full recovery. In case of severe extrapyramidal syndrome, 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 disorders.

Common: hyperprolactinemia.

Psychiatric disorders.

Common: insomnia.

Frequency unknown: confusion.

Nervous system disorders.

Common: sedative effect or drowsiness; extrapyramidal syndrome, which is partially reversible upon administration of anticholinergic antiparkinsonian agents; 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 such cases antiparkinsonian drugs are ineffective and may worsen clinical manifestations.

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

Metabolism and nutrition disorders.

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

Cardiac disorders.

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

Frequency unknown: QT interval prolongation, sudden death (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 CNS depressants).

Gastrointestinal disorders.

Common: constipation.

Uncommon: hypersalivation.

Hepatobiliary disorders.

Common: increased liver enzyme activity.

Frequency unknown: hepatocellular, cholestatic or mixed liver injury.

Musculoskeletal and connective tissue disorders.

Frequency unknown: rhabdomyolysis.

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.

Frequency unknown: increased body temperature (see section "Special precautions for use").

Investigations.

Frequency unknown: increased blood creatine phosphokinase levels.

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. Keep out of the reach of children. Store in the original packaging at a temperature not exceeding 30 °C.

Packaging.

No. 30 (15 × 2): 15 capsules in a blister; 2 blisters in a cardboard box.

No. 30 (30 × 1): 30 capsules in a blister; 1 blister in a cardboard box.

Prescription category. Prescription only.

Manufacturer. DELPHARM DIJON.

Manufacturer's address. 6 Boulevard de l'Europe, QUETIGNY, 21800, France.