Eglonil®

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

Composition:

Active ingredient: sulpiride;

One tablet contains 200 mg of sulpiride;

Excipients: potato starch, lactose monohydrate, methylcellulose, colloidal anhydrous silicon dioxide, talc, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or ivory-colored, round tablets with a dividing line on one side and engraving on the other.

Pharmacotherapeutic group. Antipsychotic agents. ATC code: N05AL01.

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 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 variations; sulpiride exhibits a linear pharmacokinetic profile after administration in doses ranging from 50 to 300 mg.

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

Sulpiride is detected in negligible amounts in breast milk and may cross the placental barrier.

Sulpiride is practically not metabolized in the human body.

Sulpiride is primarily 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.

Acute mental disorders. Chronic mental disorders (schizophrenia, chronic non-schizophrenic delusional disorders: 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 have additive central nervous system depressant effects and may lead to reduced mental alertness. These include morphine derivatives (analgesics, antitussives and substitution 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, with or 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.

These include, in particular, Class Ia and Class III antiarrhythmic agents and some neuroleptic agents. This effect may also be induced by other medicinal products not belonging to these classes.

Dolasetron, erythromycin, spiramycin and vinpocetine are involved in such interactions only in intravenous dosage forms.

Concomitant administration of two "torsadogenic" (inducing 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 included 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.

Agonists of dopamine receptors not used for the treatment of Parkinson's disease (cabergoline, quinagolide)

There is a mutual antagonism between the effects of dopamine agonists and neuroleptics.

Domperidone

Increased risk of ventricular arrhythmia, particularly torsades de pointes.

Hydroxyzine

Increased risk of ventricular arrhythmia, particularly torsades de pointes.

Piperaquine

Increased risk of ventricular arrhythmia, particularly torsades de pointes.

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. If possible, one of these two agents should be discontinued.

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

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

There is a 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 and eventually discontinued (abrupt withdrawal may expose the patient to the risk of neuroleptic malignant syndrome).

Other agents that may induce torsades de pointes (Class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide) and Class III (amiodarone, dronedarone, sotalol, dofetilide, ibutilide) and other agents such as arsenic compounds, diphenidol, intravenous dolasetron, domperidone, intravenous erythromycin, hydroxychloroquine, levofloxacin, mequitazine, mizolastine, prucalopride, intravenous vinpocetine, moxifloxacin, intravenous spiramycin, toremifene and vandetanib)

High risk of ventricular arrhythmias, particularly torsades de pointes.

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

High risk of ventricular arrhythmias, particularly torsades de pointes.

Alcohol (beverage or excipient)

Potentiation of sedative effects of neuroleptic agents.

Due to impaired concentration ability, driving vehicles and operating machinery may be hazardous. Patients should avoid consuming alcoholic beverages or using 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.

Combinations requiring caution

Anagrelide

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

Azithromycin

Increased risk of ventricular arrhythmias, particularly torsades de pointes. 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. Clinical monitoring and ECG control are required.

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

Increased risk of ventricular arrhythmias, particularly torsades de pointes. Clinical monitoring and ECG control are required.

Cyprofloxacin, levofloxacin, norfloxacin

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

Clarithromycin

Increased risk of ventricular arrhythmias, particularly torsades de pointes. 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.

Any existing hypokalaemia should be corrected before administration. Clinical monitoring and monitoring 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 therapy. If early signs of neurotoxicity appear, one of the two agents should be discontinued.

Ondansetron

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

Roxithromycin

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

Sucralfate

Reduced gastrointestinal absorption of sulpiride.

A time interval (more than 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.

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

Combinations to be considered

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 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 treatment efficacy when used concomitantly with orlistat.

Special precautions for use.

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

Except in special circumstances, 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 during sulpiride treatment is required for:

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

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

Potentially fatal neuroleptic malignant syndrome. Neuroleptic malignant syndrome is a potentially fatal complication reported during therapy with neuroleptics and is characterized by hyperthermia, pallor, autonomic dysfunction, altered consciousness, muscle rigidity, rhabdomyolysis, elevated serum creatine phosphokinase levels, and autonomic instability. Cases with atypical features, such as elevated body temperature 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, sulpiride therapy and all other neuroleptics should be discontinued immediately under medical supervision.

Signs of autonomic nervous system dysfunction, such as increased 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 is known to increase the risk of serious ventricular arrhythmias, including 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 causing QT interval prolongation), see section "Side effects".

Therefore, before initiating treatment and if clinically feasible, patients should be evaluated for risk factors that may predispose to this type of arrhythmia: bradycardia less than 55 beats per minute, hypokalemia, congenital QT interval prolongation, or 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 antipsychotic agents or in other patient populations cannot be ruled out. This medicinal product should be prescribed with caution to patients with risk factors for stroke.

Elderly patients with dementia

The risk of death is increased in elderly patients suffering from 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 treatment group compared to 2.6% in the placebo group.

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

Observational studies suggest that treatment with conventional antipsychotics may increase mortality similarly to 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 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 Egilonil®, and preventive measures should be taken (see section "Side effects").

Breast cancer. Since sulpiride may increase prolactin levels, it should be used with caution. Regardless of sex, all patients 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 causing reduced 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. The development of paralytic or mechanical intestinal obstruction requires immediate medical intervention.

When using this medicinal product, even at low doses, the risk of developing tardive dyskinesia should be considered, particularly in elderly patients.

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 "Side effects".

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

Egilonil® should be used with caution in patients with arterial hypertension, especially elderly patients, due to the risk of hypertensive crisis. Therefore, appropriate monitoring of such patients 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 animals, 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 for use in pregnant women and women of childbearing potential who are not using effective contraception, except when the expected benefits of sulpiride treatment outweigh the potential risks. Newborns 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 distress, and feeding difficulties. Therefore, newborns should be closely monitored.

Breastfeeding period. Sulpiride is excreted in breast milk in relatively large amounts. In some cases, the concentration exceeds 10% of the dose adjusted for the mother's body weight. However, the concentration in infants' blood has not been determined. There is insufficient data on the effects of sulpiride on newborns and infants.

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

Ability to influence 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 "Side effects"). Driving vehicles and operating machinery are contraindicated during treatment with this medicinal product.

Dosage and Administration

For oral use.

The lowest effective dose should always be prescribed. If the patient's clinical condition allows, treatment should be initiated at a low dose, followed by gradual dose titration.

This medicinal form is intended only for adult patients.

The daily dose ranges from 200–1000 mg.

Children

This medicinal form of the drug is intended only for adults.

Overdose

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

Fatal cases have been mainly reported 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) 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: leucopenia.

Frequency unknown: neutropenia, agranulocytosis.

Immune system disorders.

Frequency unknown: anaphylactic reactions such as urticaria, anaphylactic shock.

Endocrine 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 agents; parkinsonism; tremor; akathisia.

Uncommon: hypertonia, dyskinesia, dystonia.

Rare: oculogyric crisis.

Frequency unknown: potentially fatal neuroleptic malignant syndrome (see section "Special precautions"), 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").

Metabolic and nutritional disorders.

Frequency unknown: hyponatraemia, inadequate secretion of antidiuretic hormone.

Cardiac disorders.

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

Frequency unknown: QT interval prolongation, sudden death (see section "Special precautions").

Vascular disorders.

Uncommon: orthostatic hypotension.

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

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, perinatal and postnatal periods.

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.

Common: weight gain.

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

Investigations.

Frequency unknown: increased blood creatine phosphokinase levels.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued 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 reach and sight of children. Store at temperatures not exceeding 30 °C.

Packaging. No 12 (12 × 1): 12 tablets in a blister, 1 blister in a cardboard box.

Prescription category. Prescription only.

Manufacturer. DELPHARM DIJON.

Manufacturer's address and place of business.

6 Boulevard de l'Europe, Quetigny, 21800, France.