Eglonyl^® (Tablets, Capsules, Solution) Instructions for Use

ATC Code

N05AL01 (Sulpiride)

Active Substance

Sulpiride (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Antipsychotic agent (neuroleptic)

Pharmacological Action

Sulpiride is an atypical neuroleptic from the group of substituted benzamides that blocks dopaminergic neurotransmission in the brain (Sulpiride primarily blocks dopaminergic receptors of the limbic system, with little effect on those in the neostriatal system). The neuroleptic effect is associated with antidopaminergic action. In addition, Sulpiride has a CNS-activating effect due to a dopamine-mimetic effect. Therefore, Sulpiride has moderate neuroleptic activity combined with stimulating and thymoanaleptic (antidepressant) action.

The antipsychotic action of sulpiride manifests at doses above 600 mg/day, while at doses up to 600 mg/day, the stimulating and antidepressant action predominates.

Sulpiride does not have a significant effect on adrenergic, cholinergic, serotonergic, histaminergic, and GABA receptors.

Sulpiride stimulates prolactin secretion and has a central antiemetic effect due to the blockade of dopamine D₂ receptors in the trigger zone of the vomiting center.

Pharmacokinetics

Absorption

After oral administration of one 50 mg capsule, C_max of sulpiride in plasma is reached in 3-6 hours and is 0.25 mg/L. The bioavailability of sulpiride after oral administration is 25-35% and is characterized by significant individual variability. The pharmacokinetics of sulpiride remain linear in the dose range from 50 to 300 mg.

Distribution

Sulpiride is rapidly distributed into tissues: V_d at steady state is 0.94 L/kg. Binding to plasma proteins is approximately 40%. A small amount of sulpiride penetrates into breast milk and crosses the placental barrier.

Metabolism

In the human body, Sulpiride is only minimally metabolized.

Elimination

Sulpiride is excreted primarily by the kidneys unchanged via glomerular filtration. The total clearance is 126 ml/min. The T_1/2 of the drug from plasma is 7 hours.

Indications

• Anxiety disorders in adults (short-term symptomatic treatment when conventional treatments are ineffective);
• Severe behavioral disorders (agitation, self-harm, stereotypy) in children over 6 years of age, especially with autism spectrum disorders.

ICD codes

Dosage Regimen

Solution

The drug in the form of a solution for intramuscular injection is intended for use only in adults.

In all cases, the minimum effective doses of the drug should be used. If the patient’s clinical condition allows, treatment should be started with low doses. The minimum effective dose is selected by gradually increasing the dose until the desired effect is achieved.

The daily dose ranges from 400 to 800 mg for 2 weeks.

Elderly patients

The initial dose of sulpiride should be 1/4 to 1/2 of the adult dose.

Patients with renal impairment

Since Sulpiride is eliminated from the body primarily through the kidneys, it is recommended to reduce the dose of sulpiride and/or increase the interval between individual doses of the drug depending on the CrCl values: with CrCl 30-60 ml/min, the dose of sulpiride should be reduced by 30%, and the intervals between doses should be increased by 1.5 times; with CrCl 10-30 ml/min, the dose of sulpiride should be halved, and the intervals between doses should be doubled; with CrCl less than 10 ml/min, the dose of sulpiride should be reduced by 70%, and the intervals between doses should be tripled.

Capsules

The drug is taken orally with a small amount of liquid, regardless of meals.

In all cases, the minimum effective doses of the drug should be used. If the patient’s clinical condition allows, treatment should be started with low doses. The minimum effective dose is selected by gradually increasing the dose until the desired effect is achieved.

Adults

Short-term symptomatic treatment of anxiety disorders when conventional treatments are ineffective the daily dose is 50-150 mg for no more than 4 weeks.

Children over 6 years of age

Severe behavioral disorders (agitation, self-harm, stereotypy) especially with autism spectrum disorders the daily dose is 5-10 mg/kg of body weight.

Elderly patients

The initial dose of sulpiride should be 1/4 to 1/2 of the adult dose.

Patients with renal impairment

Since Sulpiride is eliminated from the body primarily through the kidneys, it is recommended to reduce the dose of sulpiride and/or increase the interval between individual doses of the drug depending on the CrCl values: with CrCl 30-60 ml/min, the dose of sulpiride should be reduced by 30%, and the intervals between doses should be increased by 1.5 times; with CrCl 10-30 ml/min, the dose of sulpiride should be halved, and the intervals between doses should be doubled; with CrCl less than 10 ml/min, the dose of sulpiride should be reduced by 70%, and the intervals between doses should be tripled.

Tablets

The drug in tablet form is intended for use only in adults.

The tablets are taken orally with a small amount of liquid, regardless of meals.

In all cases, the minimum effective doses of the drug should be used. If the patient’s clinical condition allows, treatment should be started with low doses. The minimum effective dose is selected by gradually increasing the dose until the desired effect is achieved.

The daily dose is divided into several administrations and ranges from 200 to 1000 mg. It is not recommended to take the drug in the afternoon (after 4 PM) due to its potential activating effect.

Elderly patients

The initial dose of sulpiride should be 1/4 to 1/2 of the adult dose.

Patients with renal impairment

Since Sulpiride is eliminated from the body primarily through the kidneys, it is recommended to reduce the dose of sulpiride and/or increase the interval between individual doses of the drug depending on the CrCl values: with CrCl 30-60 ml/min, the dose of sulpiride should be reduced by 30%, and the intervals between doses should be increased by 1.5 times; with CrCl 10-30 ml/min, the dose of sulpiride should be halved, and the intervals between doses should be doubled; with CrCl less than 10 ml/min, the dose of sulpiride should be reduced by 70%, and the intervals between doses should be tripled.

Adverse Reactions

Classification of adverse reactions (AR) by frequency of occurrence, according to WHO recommendations: very common (≥10%); common (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and <0.1%); very rare (<0.01%); frequency unknown (cannot be estimated from the available data).

ARs developing as a result of taking sulpiride are similar to ARs caused by other neuroleptics, but their frequency is generally lower.

Cardiac disorders rare – ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia; frequency unknown – QT interval prolongation, torsades de pointes, cardiac arrest, sudden death.

Vascular disorders uncommon – orthostatic hypotension; frequency unknown – venous thromboembolic complications, including pulmonary embolism and deep vein thrombosis, sometimes fatal; increased blood pressure.

Respiratory, thoracic and mediastinal disorders frequency unknown – aspiration pneumonia (when used concomitantly with other CNS depressants).

Endocrine disorders common – hyperprolactinemia.

Metabolism and nutrition disorders frequency unknown – hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Gastrointestinal disorders common – constipation; uncommon – hypersalivation.

Hepatobiliary disorders common – increased liver enzyme activity; frequency unknown – liver injury (hepatocellular, cholestatic, or mixed).

Nervous system disorders common – sedative effect or drowsiness, extrapyramidal disorders (these symptoms are usually reversible after the administration of antiparkinsonian drugs), parkinsonism, tremor, akathisia; uncommon – muscle hypertonia, dyskinesia, muscle dystonia; rare – oculogyric crisis; frequency unknown – neuroleptic malignant syndrome (NMS), hypokinesia, tardive dyskinesia (as with all neuroleptics, after their use for more than 3 months; in this case, the use of antiparkinsonian drugs is ineffective or may exacerbate symptoms), seizures.

Psychiatric disorders common – insomnia; frequency unknown – confusion.

Reproductive system and breast disorders common – breast pain, galactorrhea; uncommon – breast enlargement, amenorrhea, orgasmic dysfunction, erectile dysfunction; frequency unknown – gynecomastia.

Skin and subcutaneous tissue disorders common – maculopapular rash.

Musculoskeletal and connective tissue disorders frequency unknown – torticollis, trismus, rhabdomyolysis.

Blood and lymphatic system disorders uncommon – leukopenia; frequency unknown – neutropenia, agranulocytosis.

Immune system disorders frequency unknown – anaphylactic reactions (urticaria, dyspnea, excessive decrease in blood pressure, anaphylactic shock).

Pregnancy, puerperium and perinatal conditions frequency unknown – extrapyramidal symptoms, withdrawal syndrome in newborns (see section “Pregnancy and lactation”).

Investigations frequency unknown – increased serum creatine phosphokinase (CPK) concentration.

General disorders and administration site conditions common – weight increased; frequency unknown – hyperthermia.

Contraindications

• Hypersensitivity to sulpiride or any excipient of the drug;
• Prolactin-dependent tumors (pituitary prolactinomas and breast cancer);
• Hyperprolactinemia;
• Pheochromocytoma;
• Acute porphyria;
• Acute intoxication with alcohol (ethanol), hypnotics, narcotic analgesics;
• Children under 6 years of age (for this dosage form);
• Breastfeeding period;
• Congenital galactosemia, glucose/galactose malabsorption syndrome or lactase deficiency (due to the presence of lactose in the drug composition);
• Concomitant use of levodopa (see section “Drug Interactions”);
• Concomitant therapy with dopamine receptor agonists (cabergoline, quinagolide, ropinirole, rotigotine) (see section “Drug Interactions”).

With caution

• In patients predisposed to developing cardiac arrhythmias, because Sulpiride may cause QT interval prolongation and increase the risk of severe ventricular arrhythmias, such as torsades de pointes:
  • With bradycardia less than 55 beats/min;
  • With electrolyte disturbances, especially hypokalemia;
  • With congenital long QT syndrome;
  • Concomitantly receiving drugs that can cause significant bradycardia (less than 55 beats/min), hypokalemia, slowed intracardiac conduction, or QT interval prolongation (see sections “Drug Interactions”, “Special Precautions”).
• In patients with a history of neuroleptic malignant syndrome (see sections “Adverse Reactions”, “Special Precautions”);
• In elderly patients (increased risk of sedation, orthostatic hypotension, extrapyramidal disorders);
• Aggressive behavior or agitation with impulsivity (concomitant use of sedative drugs may be required);
• In elderly patients with dementia (see section “Special Precautions”);
• In patients with risk factors for stroke (see section “Special Precautions”);
• In patients with Parkinson’s disease (see section “Special Precautions”);
• In patients with risk factors for venous thromboembolic complications (see section “Special Precautions”);
• In diabetes mellitus and in the presence of risk factors for diabetes mellitus (risk of hyperglycemia, blood glucose monitoring required);
• During pregnancy (limited experience of use) (see section “Pregnancy and Lactation”);
• In renal failure (dosing regimen adjustment required, see section “Dosage Regimen”);
• In epilepsy or a history of seizures (risk of lowered seizure threshold) (see section “Special Precautions”);
• With concomitant use of medicinal products containing ethanol (see section “Drug Interactions”);
• In patients with a history of glaucoma, intestinal obstruction, congenital stenosis of the digestive tract, urinary retention, or prostatic hyperplasia;
• In patients (especially elderly patients) with arterial hypertension due to the risk of hypertensive crisis (patients should be under medical supervision);
• In patients with a history (including family history) of breast cancer (see section “Special Precautions”);
• When used in children, caution should be exercised, as the efficacy and safety of sulpiride in this category of patients have not been sufficiently studied (see section “Special Precautions”).

Use in Pregnancy and Lactation

Pregnancy

There is very limited clinical data on the use of sulpiride in women during pregnancy. Sulpiride crosses the placental barrier. The use of the drug is not recommended during pregnancy and in women of reproductive age not using effective contraception and planning pregnancy, except in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

Newborns who were exposed to antipsychotic drugs, including Eglonyl^®, during the third trimester of pregnancy are at risk of developing adverse reactions after birth, including extrapyramidal symptoms or withdrawal syndrome, which may vary in severity and duration (see section “Adverse Reactions”). Agitation, hypertonia, hypotonia, tremor, drowsiness, respiratory distress, or feeding disorders have been reported. Therefore, newborns should be under constant medical supervision.

Breastfeeding period

Sulpiride passes into human breast milk, breastfeeding during treatment with sulpiride is contraindicated.

Preclinical data

In studies conducted on animals, Sulpiride did not demonstrate direct or indirect teratogenic or embryotoxic effects.

Fertility

A decrease in fertility associated with the pharmacological effects of sulpiride (a prolactin-mediated effect) was observed in animals.

Use in Renal Impairment

The drug should be used with caution in renal failure.

Pediatric Use

Contraindicated for use in children under 6 years of age (for this dosage form).

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal complication and can occur with the use of any neuroleptic, is characterized by pallor, hyperthermia, muscle rigidity, autonomic nervous system dysfunction, and impaired consciousness. Signs of autonomic nervous system dysfunction, such as increased sweating and lability of blood pressure and pulse, may precede the onset of hyperthermia and be early warning symptoms. Cases with atypical manifestations of NMS without rigidity and increased muscle tone have been observed. In case of hyperthermia of unknown origin, which can be considered either an early sign/symptom of NMS or an atypical NMS, Sulpiride should be discontinued immediately and medical supervision of the patient should be established. The cause of NMS remains unclear. It is assumed that the blockade of dopamine receptors in the striatum and hypothalamus plays a role in its mechanism, and an innate predisposition (idiosyncrasy) is also not excluded. Intercurrent infection, dehydration, or organic brain damage may contribute to the development of the syndrome.

QT interval prolongation

Sulpiride may cause QT interval prolongation. This effect is known to increase the risk of severe ventricular arrhythmias, such as torsades de pointes.

Before using the drug, if the patient’s condition allows, the presence of factors predisposing to the development of these severe arrhythmias should be excluded (bradycardia less than 55 beats/min; electrolyte disturbances, especially hypokalemia, hypomagnesemia; congenital long QT syndrome; concomitant use of drugs causing significant bradycardia (less than 55 beats/min), hypokalemia, slowed intracardiac conduction, or QT interval prolongation.

Caution should be exercised when prescribing sulpiride to patients with the above risk factors if necessary. Hypokalemia and hypomagnesemia should be corrected before starting the drug; in addition, medical supervision and regular monitoring of blood electrolytes and ECG should be ensured.

Except in cases of urgent intervention, patients requiring treatment with neuroleptics are recommended to undergo assessment and ECG monitoring.

Extrapyramidal syndrome

For neuroleptic-induced extrapyramidal syndrome, m-cholinoblocking drugs (and not dopamine receptor agonists) should be prescribed (see section “Drug Interactions”).

Patients with Parkinson’s disease or dementia with Lewy bodies should be prescribed Eglonyl^® only in cases of extreme necessity (due to an increased risk of developing or exacerbating symptoms of extrapyramidal disorders).

Stroke

In randomized clinical trials comparing some atypical antipsychotics with placebo, conducted in elderly patients with dementia, a threefold increase in the risk of cerebrovascular complications was observed. The mechanism of this risk is unknown. An increase in such risk with other antipsychotics or in other patient populations cannot be excluded, therefore Sulpiride should be prescribed with caution to patients with risk factors for stroke.

Elderly patients with dementia

In elderly patients with psychosis associated with dementia, treatment with antipsychotic drugs was associated with an increased risk of death. An analysis of 17 placebo-controlled studies (with a median duration of over 10 weeks) showed that the majority of patients receiving atypical antipsychotic drugs had a 1.6-1.7 times greater risk of death than patients receiving placebo.

In a 10-week placebo-controlled trial, the mortality rate for such patients taking atypical antipsychotics was 4.5%, compared to 2.6% for placebo.

Although the causes of death in clinical trials with atypical antipsychotic drugs varied, most deaths were either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies have confirmed that, similar to treatment with atypical antipsychotics, treatment with conventional antipsychotics may also increase mortality. The extent to which the increased mortality may be attributed to the antipsychotic drug rather than to certain patient characteristics is unclear.

Venous thromboembolic complications

Cases of venous thromboembolic complications, sometimes fatal, have been observed during the use of antipsychotic drugs. Therefore, Sulpiride should be used with caution in patients with risk factors for developing venous thromboembolic complications.

Breast cancer

Sulpiride may increase plasma prolactin concentration. Therefore, caution should be exercised when using sulpiride in patients with a history (including family history) of breast cancer. Such patients should be under close observation.

Patients with epilepsy

Since antipsychotics can lower the epileptogenic threshold, patients with epilepsy prescribed sulpiride should be under strict medical supervision.

Patients with Parkinson’s disease taking dopamine receptor agonists

Except in exceptional cases, Eglonyl^® should not be used in patients with Parkinson’s disease. If there is an urgent need for antipsychotic treatment in patients with Parkinson’s disease who are taking dopamine receptor agonists, the doses of the latter should be gradually reduced until complete withdrawal (abrupt withdrawal of dopamine receptor agonists may increase the risk of developing NMS in the patient).

Patients with impaired renal function

Reduced doses should be used.

Patients with diabetes mellitus or with risk factors for developing diabetes mellitus

Since hyperglycemia has been reported in patients taking atypical antipsychotic drugs, patients with an established diagnosis of diabetes or with risk factors for its development who are prescribed sulpiride treatment should have their blood glucose concentration monitored.

Ethanol consumption

Consumption of alcoholic beverages containing ethanol, or use of medicinal products containing ethanol, during treatment with Eglonyl^® is strictly prohibited.

Leukopenia, neutropenia and agranulocytosis

Leukopenia, neutropenia, and agranulocytosis have been reported during therapy with antipsychotics, including Eglonyl^®. The development of unexplained infections or fever may be signs of blood disorders, requiring immediate hematological investigations.

Use in pediatrics

Due to the effect of sulpiride on cognitive processes in children, learning ability should be monitored annually. The dose should be regularly adjusted according to the child’s clinical condition.

Effect on the ability to drive vehicles and operate machinery

During treatment with Eglonyl^®, driving vehicles and engaging in other potentially hazardous activities requiring attention and speed of psychomotor reactions are prohibited (since even at recommended doses, the drug may have a sedative effect).

Overdose

Experience with sulpiride overdose is limited.

Specific symptoms are absent; the following may be observed: dyskinesia with spastic torticollis, tongue protrusion, and trismus. In some patients – life-threatening parkinsonian syndrome and coma.

Treatment Sulpiride is partially removed by hemodialysis. Due to the lack of a specific antidote, symptomatic and supportive therapy should be applied, with careful monitoring of respiratory function and continuous monitoring of cardiac activity (risk of QT interval prolongation and development of ventricular arrhythmias), which should continue until the patient’s complete recovery; in case of severe extrapyramidal syndrome, m-anticholinergics are prescribed.

There have been reports of fatal outcomes in overdose, mainly when sulpiride was combined with other psychotropic agents.

Drug Interactions

Contraindicated combinations

With levodopa mutual antagonism of the effects of levodopa and antipsychotics.

With dopamine receptor agonists (cabergoline, quinagolide, ropinirole, rotigotine) mutual antagonism between dopamine receptor agonists and antipsychotics (see sections “Contraindications”, “Special Instructions”).

Not recommended combinations

With ethanol ethanol enhances the sedative effect of antipsychotics. Consumption of alcoholic beverages and medicinal products containing ethanol should be avoided.

With drugs capable of prolonging the QT interval or causing the development of torsades de pointes ventricular tachycardia

• Drugs causing bradycardia: beta-blockers; heart rate-lowering slow calcium channel blockers (verapamil, diltiazem); clonidine, guanfacine; cardiac glycosides;
• Drugs causing hypokalemia: diuretics that reduce blood potassium concentration; stimulant laxatives; intravenous amphotericin B; corticosteroids; tetracosactide (hypokalemia must be corrected before taking sulpiride);
• Class IA antiarrhythmic drugs such as quinidine, disopyramide;
• Class III antiarrhythmic drugs such as amiodarone, sotalol, dofetilide, ibutilide;
• Other drugs such as pimozide; amisulpride; sultopride; tiapride; haloperidol; thioridazine; methadone; chlorpromazine; droperidol; cyamemazine; pipotiazine; sertindole; levomepromazine; imipramine-derived antidepressants; lithium preparations; bepridil; cisapride; intravenous erythromycin; intravenous vincamine; intravenous spiramycin; moxifloxacin; levofloxacin; mizolastine; diphemanil; halofantrine; pentamidine; lumefantrine; sparfloxacin; clarithromycin; roxithromycin; azithromycin;
• Selective serotonin reuptake inhibitors (citalopram, escitalopram).

If simultaneous use of these drugs with sulpiride cannot be avoided in patients, careful clinical, laboratory (monitoring of blood electrolyte composition) and electrocardiographic monitoring should be conducted.

Interaction to be taken into account

With antihypertensive drugs, nitrates and nitrate derivatives additive hypotensive effect, increased risk of orthostatic hypotension.

With drugs that depress CNS function morphine derivatives (analgesics, antitussives); sedating histamine H₁-receptor blockers; barbiturates; benzodiazepines and other anxiolytics; hypnotics; sedating antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); centrally acting antihypertensive agents (clonidine and other centrally acting antihypertensive drugs); baclofen; thalidomide – a pronounced enhancement of the CNS depressant effect and a decrease in psychomotor reaction are possible.

With antacids and sucralfate simultaneous use reduces the absorption of sulpiride, therefore, when sulpiride and antacids or sucralfate are used concomitantly, a minimum two-hour interval between their intake is required.

With lithium preparations increased risk of extrapyramidal adverse reactions. At the first signs of neurotoxicity, the administration of both drugs should be discontinued.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.