Eglonil®

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

Composition:

Active substance: sulpiride;

100 mg of sulpiride in 2 ml of solution;

Excipients: sulfuric acid of pharmaceutical purity, sodium chloride, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or practically colorless, odorless or practically odorless liquid.

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 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 of sulpiride is 40%.

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

Sulpiride is primarily eliminated 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 treatment of agitation and aggression in patients with acute and chronic mental disorders (schizophrenia, chronic non-schizophrenic delirium: paranoid delusion, chronic hallucinatory psychosis).

Contraindications.

Eglonyl® is contraindicated in the following cases:

• 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 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").

Interaction with other medicinal products and other forms of interaction.

Sedative agents

It should be borne in mind 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), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally-acting antihypertensive agents, baclofen and thalidomide.

Medicinal products that may induce torsade 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 agents of class Ia and class III, and some neuroleptics. This effect is also induced by other medicinal products not belonging to these classes.

The interaction involves dolasetron, erythromycin, spiramycin and vinca alkaloids only in intravenous dosage forms.

Concomitant administration of two "torsadogenic" (those causing 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 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 torsade de pointes (paroxysmal ventricular tachycardia of the "twisting of the points" type).

Non-antiparkinsonian dopamine receptor agonists (cabergoline, quinagolide)

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

Domperidone

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

Hydroxyzine

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

Piperaquine

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

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

Antiparasitic agents that may induce torsade de pointes (paroxysmal ventricular tachycardia of the "twisting of the points" type) (chloroquine, halofantrine, lumefantrine, pentamidine)

Increased risk of ventricular arrhythmias, particularly torsade de pointes (paroxysmal ventricular tachycardia of the "twisting of the points" 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 of treatment and ECG monitoring should be performed during treatment.

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 exposes the patient to the risk of neuroleptic malignant syndrome).

Other medicinal products that may induce torsade de pointes (paroxysmal ventricular tachycardia of the "twisting of the points" type) (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 vinca alkaloids, moxifloxacin, intravenous spiramycin, toremifene and vandetanib)

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

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

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

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 consumption of alcoholic beverages or use of medicinal products containing alcohol.

Levodopa

There is a mutual antagonism 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 torsade de pointes (paroxysmal ventricular tachycardia of the "twisting of the points" type).

Combinations requiring caution

Anagrelide

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

Azithromycin

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

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

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

Agents causing bradycardia (such as class Ia antiarrhythmics, beta-blockers, some class III antiarrhythmics, certain calcium channel blockers, crizotinib, digitalis glycosides, pasireotide, pilocarpine, anticholinesterase agents)

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

Cyprofl oxacin, levofloxacin, norfloxacin

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

Clarithromycin

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

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

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

Prior to administration, existing hypokalaemia should be corrected, and clinical monitoring, electrolyte control and ECG monitoring should be performed.

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, discontinuation of one of the two medicinal products is recommended.

Ondansetron

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

Roxithromycin

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

Combinations to be considered

Other sedative agents

Enhanced 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 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.

More careful monitoring is required during sulpiride therapy 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 Egolnil®. Infections of unknown etiology or unexplained fever may be signs of leukopenia (see section "Side effects"); in such cases, a blood test should be performed immediately.

Potentially fatal neuroleptic malignant syndrome. Neuroleptic malignant syndrome is a potentially fatal complication reported during therapy with neuroleptics, 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 or 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 dysfunction, such as excessive sweating and blood pressure changes, may develop prior to hyperthermia and should therefore be considered as early warning symptoms. Although this neuroleptic effect may be idiosyncratic, risk factors such as dehydration and organic brain damage may be present.

QT interval prolongation. Sulpiride may cause dose-dependent prolongation of the QT interval. This effect, 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 prolongs the QT interval) (see section "Side effects").

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

Except in emergency situations, ECG monitoring is recommended during the initial evaluation of patients scheduled to receive neuroleptic therapy.

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 other antipsychotics 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 with psychosis associated with dementia who are treated with antipsychotic agents.

Analysis of data from 17 placebo-controlled trials (with a mean duration of 10 weeks) involving patients receiving atypical antipsychotics showed a 1.6–1.7 times higher risk of death in patients treated with these drugs compared to 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 deaths were due to cardiovascular (e.g., heart failure, sudden death) or infectious conditions (e.g., pneumonia).

Observational studies suggest that treatment with conventional antipsychotics may also increase mortality similarly to atypical antipsychotics.

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

Venous thromboembolism. Cases of venous thromboembolism (VTE) have been reported during antipsychotic therapy. Since patients taking antipsychotics often have acquired risk factors for VTE, all potential risk factors for VTE should be assessed before and during treatment with Egolnil®, and preventive measures should be taken (see section "Side effects").

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 therapy.

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. Development of paralytic or mechanical intestinal obstruction requires immediate medical intervention.

Even when used 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 "Interaction with other medicinal products and other forms of interaction").

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

Egolnil® should be used cautiously in patients with arterial hypertension, particularly elderly patients, due to the risk of hypertensive crisis. Therefore, appropriate monitoring of such patients is required.

This medicinal product contains 30 mg of sodium per dose. This should be taken into account for patients on a strict low-sodium 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. There is very limited data on the use of sulpiride during pregnancy. 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 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. Intravenous administration of neuroleptics may lead to hypotension in pregnant women. Newborns whose mothers received antipsychotics during the third trimester of pregnancy are at risk of developing adverse effects, 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, newborns should be carefully monitored.

Breastfeeding period. Sulpiride is excreted in breast milk in relatively large amounts. In some cases, concentrations exceed 10% of the dose adjusted for maternal body weight. However, sulpiride concentrations in infant blood have 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 therapy 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 or operating machinery is contraindicated during treatment with this medicinal product.

Dosage and Administration

The drug is administered intramuscularly.

It is intended only for adult patients.

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 if necessary.

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

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

Children

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

Overdose

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

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

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 maintained until full recovery of the patient. In case of severe extrapyramidal symptoms, anticholinergic drugs should be administered.

Adverse Reactions

Blood and lymphatic system disorders

Uncommon: leukopenia.

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 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: hyponatremia, inadequate antidiuretic hormone secretion.

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 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: galactorrhea.

Uncommon: amenorrhea, impotence or frigidity.

Frequency unknown: gynecomastia.

General disorders and administration site conditions

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 ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals are required to report any suspected adverse reactions via the adverse reaction reporting system in Ukraine.

Shelf life

3 years.

Storage conditions Store out of reach of children. No special storage conditions required.

Packaging No. 6: 2 ml in an ampoule, 6 ampoules in blister packs in a cardboard box.

Prescription status Prescription only.

Manufacturer DELPHARM DIJON.

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