Instructions Sulpiride capsules 50 mg No. 24
Composition
active ingredient: sulpiride;
1 capsule contains sulpiride 50 mg or 100 mg;
excipients: colloidal anhydrous silicon dioxide, corn starch, lactose monohydrate, magnesium stearate;
hard gelatin capsule for 50 mg: gelatin, titanium dioxide (E 171);
hard gelatin capsule for 100 mg: gelatin, titanium dioxide (E 171), quinoline yellow (E 104), iron oxide red (E 172).
Dosage form
The capsules are hard.
Main physicochemical properties:
50 mg capsules: cylindrical capsules with semicircular edges, number 3, white, filled with white or cream-colored powder;
100 mg capsules: cylindrical capsules with semicircular edges, number 3, yellow, filled with white or cream-colored powder.
Pharmacotherapeutic group
Antipsychotics. Benzamides. ATX code N05A L01.
Pharmacological properties
Pharmacodynamics.
Sulpiride acts on dopaminergic neurotransmission in the brain as a dopaminomimetic, thereby exerting an activating effect at low doses. At higher doses, sulpiride also reduces productive symptoms.
Sulpiride activates the secretion of prolactin. The active substance improves mucus secretion and blood supply to the mucous membrane of the stomach and duodenum.
Sulpiride also exhibits antiemetic effects.
Pharmacokinetics.
Sulpiride is slowly absorbed from the gastrointestinal tract. The presence of food reduces absorption by 30%. Bioavailability is low (27-34%) and depends on individual differences. The active substance quickly enters the tissues; only a small amount of it penetrates the blood-brain barrier. The maximum concentration in the blood plasma is reached 3-6 hours after oral administration. Protein binding is about 40%, the volume of distribution is from 1 to 2.7 l / kg. The half-life from the blood plasma is about 8 hours. In patients with severe renal impairment, it is prolonged to 20-26 hours after intravenous administration. A small amount of the active substance penetrates into breast milk. It is excreted in the urine and feces mainly unchanged.
Indication
Short-term symptomatic treatment of anxiety disorders in adults when conventional therapeutic measures have failed.
Serious behavioral disorders (agitation, self-harm, stereotypy) in children aged 6 years and older, especially in patients with autistic syndromes.
Contraindication
Hypersensitivity to sulpiride or any of the excipients of the drug.
Known or suspected diagnosis of pheochromocytoma.
Acute porphyria.
Concomitant prolactin-dependent tumors (e.g., prolactin-secreting pituitary adenoma (prolactinoma) and breast cancer).
Concomitant use with dopamine receptor agonists not for the treatment of Parkinson's disease (cabergoline, quinagolide), levodopa, citalopram and escitalopram, hydroxyzine, domperidone and piperazine (see section "Interaction with other medicinal products and other types of interactions").
Breastfeeding (see section “Use during pregnancy or breastfeeding”).
Interaction with other medicinal products and other types of interactions
Sedatives
It should be remembered that many drugs or substances can have an additive inhibitory effect on the central nervous system and reduce mental performance. These drugs include morphine derivatives (analgesics, cough suppressants and substitution agents), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally acting antihypertensives, baclofen and thalidomide.
Drugs that may cause the development of paroxysmal ventricular tachycardia (torsades de pointes)
This serious cardiac arrhythmia can be caused by a number of drugs, with or without antiarrhythmic activity. Precipitating factors include hypokalemia (see “Potassium-sparing drugs” below) and bradycardia (see “Bradycardia-inducing drugs” below) or the presence of congenital or acquired QT prolongation.
These include, in particular, antiarrhythmic drugs of classes Ia and III and some neuroleptics. This effect is also induced by other drugs that do not belong to these classes.
This interaction involves dolasetron, erythromycin, spiramycin, and vincamine, only in dosage forms for intravenous administration.
The concomitant administration of two “torsadogenic” (those that cause torsades de pointes) drugs is generally contraindicated. However, some of these drugs are exceptions, as their use cannot be avoided. Therefore, they are simply not recommended for use in combination with drugs that can induce torsades de pointes. This applies to methadone, antiparasitic drugs (chloroquine, halofantrine, lumefantrine, pentamidine) and neuroleptics.
However, these exceptions do not include citalopram, domperidone, and escitalopram: their use with all drugs that can induce torsades de pointes is contraindicated.
Citalopram, escitalopram
Increased risk of developing ventricular arrhythmias, especially torsades de pointes.
Dopamine receptor agonists not for the treatment of Parkinson's disease (cabergoline, quinagolide)
There is mutual antagonism between dopamine agonists and neuroleptics.
Domperidone
There is an increased risk of developing ventricular arrhythmias, in particular torsades de pointes.
Hydroxyzine
There is an increased risk of developing ventricular arrhythmias, in particular torsades de pointes.
Piperaquin
There is an increased risk of developing ventricular arrhythmias, in particular torsades de pointes.
Undesirable combinations (see section "Special precautions for use")
Antiparasitic drugs that can cause the development of paroxysmal ventricular tachycardia (torsades de pointes) (chloroquine, halofantrine, lumefantrine, pentamidine)
Due to the increased risk of ventricular arrhythmias, in particular torsades de pointes, one of these two drugs should be discontinued if possible. If concomitant treatment cannot be avoided, the QT interval should be checked before starting treatment and ECG should be monitored during treatment.
Antiparkinsonian dopamine agonists (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, rasagiline, selegiline)
There is mutual antagonism between dopamine agonists and neuroleptics.
Dopamine agonists may cause or exacerbate psychiatric disorders. If neuroleptics are required in patients with Parkinson's disease treated with dopamine agonists, the dose of dopamine agonists should be gradually reduced (abrupt withdrawal puts the patient at risk of neuroleptic malignant syndrome).
Other drugs that may induce torsades de pointes (class Ia (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, dronedarone, sotalol, dofetilide, ibutilide) antiarrhythmics and other drugs such as arsenic compounds, diphemanil, intravenous dolasetron, domperidone, intravenous erythromycin, hydroxychloroquine, levofloxacin, mechitazine, mizolastine, prucalopride, intravenous vincamine, moxifloxacin, intravenous spiramycin, toramifene and vandetanib)
High risk of ventricular arrhythmias, particularly torsades de pointes.
Other neuroleptics that may cause the development of torsades de pointes (amisulpride, chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperon, pipothiazide, sultopride, tiapride, zuclopenthixol)
High risk of ventricular arrhythmias, in particular paroxysmal ventricular tachycardia of the "pirouette" type (torsades de pointes).
Alcohol (drink or excipient)
Potentiation of the sedative effects of neuroleptics.
Due to impaired ability to concentrate, driving vehicles and operating other machinery may be dangerous.
Patients should avoid drinking alcoholic beverages or medications that contain alcohol.
Levodopa
There is mutual antagonism between levodopa and neuroleptics.
Patients with Parkinson's disease treated with dopamine agonists and neuroleptics should be prescribed the minimum effective doses of both drugs.
Methadone
Increased risk of ventricular arrhythmias, in particular torsades de pointes.
Combinations requiring caution
Anagrelide
Increased risk of ventricular arrhythmias, especially torsades de pointes. ECG and clinical monitoring are necessary during concomitant use.
Azithromycin
Increased risk of ventricular arrhythmias, especially torsades de pointes. ECG and clinical monitoring are necessary during concomitant use.
Beta-blockers used in patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)
Increased risk of ventricular arrhythmias, including torsades de pointes. Clinical and ECG monitoring is required.
Drugs that cause bradycardia (including class Ia antiarrhythmics, beta-blockers, some class III antiarrhythmics, some calcium channel blockers, crizotinib, digitalis glycosides, pasireotide, pilocarpine, anticholinesterase drugs)
Increased risk of ventricular arrhythmias, including torsades de pointes. Clinical monitoring and ECG monitoring are required.
Ciprofloxacin, levofloxacin, norfloxacin
Increased risk of ventricular arrhythmias, especially torsades de pointes. ECG and clinical monitoring are necessary during concomitant use.
Increased risk of ventricular arrhythmias, especially torsades de pointes. ECG and clinical monitoring are necessary during concomitant use.
Potassium-sparing drugs (potassium-sparing diuretics, including combinations, stimulant laxatives, glucocorticoids, tetracosactide, and amphotericin for intravenous use)
Increased risk of developing ventricular arrhythmias, in particular paroxysmal ventricular tachycardia of the "pirouette" type (torsades de pointes).
Before administration, correction of existing hypokalemia should be performed and clinical monitoring, electrolyte levels and ECG should be performed.
Lithium
Risk of neuropsychiatric changes suggestive of neuroleptic malignant syndrome or lithium toxicity. Regular clinical and laboratory monitoring is indicated, especially at the beginning of concomitant use. At the first signs of neurotoxicity, it is recommended to discontinue one of the two drugs.
Ondansetron
Increased risk of ventricular arrhythmias, especially torsades de pointes. ECG and clinical monitoring are necessary during concomitant use.
Roxithromycin
Increased risk of ventricular arrhythmias, especially torsades de pointes. ECG and clinical monitoring are necessary during concomitant use.
Sucralfate
Reduced absorption of sulpiride in the gastrointestinal tract.
There should be a certain time interval (more than 2 hours, if possible) between the administration of sucralfate and sulpiride.
Topical gastrointestinal agents, antacids, and activated charcoal
Reduced absorption of sulpiride in the gastrointestinal tract.
There should be a certain time interval (more than 2 hours, if possible) between the administration of these drugs and sulpiride.
Combinations for which there are caveats
Other sedatives
More pronounced inhibition of central nervous system function. Due to impaired ability to concentrate, driving vehicles and working with other mechanisms may be dangerous.
Antihypertensives
Increased risk of arterial hypotension, particularly postural.
Beta-blockers used in patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)
For beta-blockers used in heart failure, see “Combinations requiring caution” above. Vasodilator effect and risk of hypotension, particularly postural (additive effect).
Dapoxetine
Risk of increased incidence of adverse effects, especially dizziness or syncope.
Orlistat
Risk of treatment failure when used concomitantly with orlistat.
Application features
In patients with diabetes mellitus or with risk factors for developing diabetes mellitus, adequate blood glucose control should be performed at the beginning of sulpiride treatment.
Except in special cases, this medicine should not be prescribed to patients with Parkinson's disease.
As with other drugs that are primarily excreted by the kidneys, dosage reduction and increased monitoring are recommended in patients with renal insufficiency; in cases of severe renal insufficiency, intermittent courses of treatment are advisable.
During treatment with sulpiride, it is necessary to monitor more closely:
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 prone to developing postural hypotension, sedation, and extrapyramidal effects of the drug.
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including sulpiride. Unexplained infections or fever may indicate blood dyscrasias and require immediate laboratory blood testing.
Potentially fatal neuroleptic malignant syndrome. In the event of an increase in body temperature of unknown etiology, treatment should be discontinued immediately, as this may be one of the symptoms of malignant syndrome that can develop while taking neuroleptics (pallor, hyperthermia, autonomic nervous system disorders, impaired consciousness, muscle rigidity).
Signs of autonomic nervous system dysfunction, such as increased sweating and changes in blood pressure, may develop before the onset of hyperthermia and should therefore be considered as early warning symptoms.
Although this effect of neuroleptics may be idiosyncratic in nature, risk factors such as dehydration and organic brain damage may be present.
Therefore, before administering the drug and if the clinical situation allows, patients should be checked for risk factors for the development of this type of arrhythmia: bradycardia less than 55 beats per minute, hypokalemia, congenital prolongation of the QT interval, concomitant treatment with a drug that can cause severe bradycardia (less than 55 beats per minute), hypokalemia, slowing of intracardiac conduction or prolongation of the QT interval (see sections “Contraindications” and “Interaction with other medicinal products and other types of interactions”).
Except in urgent cases, it is recommended that an ECG be performed during the initial assessment of patients who require treatment with a neuroleptic drug. The drug should not be taken concurrently with other neuroleptics.
Stroke. In randomized, placebo-controlled clinical trials, an increased risk of stroke was observed in elderly patients with dementia treated with some atypical antipsychotics compared with those treated with placebo. The mechanism of this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics or in other patient populations. This drug should be prescribed with caution in patients with risk factors for stroke.
Elderly patients with dementia. The risk of death is increased among elderly patients with dementia-related psychosis who are treated with antipsychotics.
Analysis of data from studies involving patients taking atypical antipsychotics in general showed that the risk of death was 1.6-1.7 times higher in patients taking these drugs compared with placebo. After a median treatment period of 10 weeks, the risk of death was 4.5% in the treated group compared with 2.6% in the placebo group.
Although the causes of deaths with atypical antipsychotics varied, the majority were due to cardiovascular disease (e.g., heart failure, sudden death) or infections (e.g., pneumonia).
Epidemiological studies suggest that treatment with standard antipsychotics may increase mortality, as does the use of atypical antipsychotics.
The respective role of antipsychotic drug and patient characteristics in increasing mortality rates in epidemiological studies remains uncertain.
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients taking antipsychotics often have acquired risk factors for VTE, all potential risk factors for VTE should be identified before and during treatment with sulpiride and preventive measures should be taken (see section 4.8).
Breast cancer. Sulpiride may increase prolactin levels. Therefore, it should be used with caution. Regardless of gender, patients with a personal or family history of breast cancer require close monitoring during sulpiride therapy.
Slowing of intestinal peristalsis. 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 of these patients were receiving concomitant treatment with one or more medicinal products known to reduce intestinal motility (including medicinal products with anticholinergic properties). Particular attention should be paid to the appearance of abdominal pain with vomiting and/or diarrhoea. It is very important to recognise constipation in time and treat it actively. The development of paralytic or mechanical intestinal obstruction requires urgent treatment.
It is not recommended to take this medicine with alcohol, levodopa, dopamine receptor agonists, antiparasitic drugs that may induce torsades de pointes, methadone, other neuroleptics and drugs that may induce torsades de pointes (see section “Interaction with other medicinal products and other forms of interaction”).
Sulpiride has an anticholinergic effect, so it should be used with caution in patients with glaucoma, intestinal obstruction, congenital stenosis of the gastrointestinal tract, urinary retention, and a history of prostatic hyperplasia.
Sulpiride should be used with caution in patients with arterial hypertension, especially in elderly patients, due to the risk of hypertensive crisis. Careful monitoring of the patient's condition is necessary.
When using the drug even at low doses, the risk of developing tardive dyskinesia should be considered, particularly in elderly patients.
Do not take sulpiride late at night, as it may disrupt sleep.
This medicinal product contains lactose and is therefore not recommended for use in patients with galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases).
Use during pregnancy or breastfeeding
Pregnancy. In animals, a decrease in fertility was observed, which is associated with the pharmacological properties of sulpiride (prolactin-mediated effect). Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development and/or postnatal development. Very limited data on effects on pregnancy are available in humans. In almost all cases of fetal or neonatal malformations reported in the context of sulpiride use during pregnancy, alternative explanations are considered to be more likely. Therefore, due to limited experience, sulpiride is not recommended during pregnancy. Adverse reactions, including extrapyramidal symptoms and/or withdrawal symptoms, of varying severity and duration, may occur in newborns whose mothers have received antipsychotics (including sulpiride) during the third trimester of pregnancy. Agitation, hypertonia, hypotension, tremor, drowsiness, respiratory distress syndrome, and feeding disturbances have been reported. Therefore, close monitoring of the neonate is necessary.
Breastfeeding: Since sulpiride is found in breast milk, breastfeeding is not recommended during treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients, especially those who drive or operate machinery, should be warned that the use of this medicinal product may cause drowsiness (see section "Adverse reactions"). Driving and operating machinery is contraindicated during use of the drug.
Method of administration and doses
For oral use.
The minimum effective dose should always be prescribed. If the patient's clinical condition permits, treatment should be initiated at a low dose, followed by gradual dose titration.
Sulpiride should be taken at least 1 hour before or 2 hours after meals.
Adults: Short-term symptomatic treatment of anxiety disorders in cases where conventional therapeutic measures have failed: daily dose is 50-150 mg for no more than 4 weeks.
Children aged 6 years and over. Serious behavioral disorders (agitation, self-harm, stereotypy), especially in patients with autistic syndromes: 5 mg/kg body weight per day (if necessary, this dose can be increased to 10 mg/kg body weight per day). Another dosage form is more suitable for children - oral solution.
Patients with renal impairment. For this group of patients, the dose should be adjusted according to the degree of renal impairment: reduce the dose or extend the interval between doses.
Children.
Since the efficacy and safety of sulpiride in children have not been fully studied, it should be used with caution (see section "Method of administration and dosage"). Due to the effect of the drug on cognitive abilities, it is recommended to conduct an annual clinical examination to assess learning ability. The dose of the drug should be adjusted periodically, based on the clinical status of the child.
The use of hard capsules is contraindicated in children under 6 years of age, as it may lead to airway obstruction.
Overdose
Experience with overdose of sulpiride is limited. Dyskinetic manifestations with spasmodic torticollis, tongue protrusion and trismus may occur. Some patients may develop life-threatening parkinsonism or even coma.
Fatal cases were recorded mainly when used in combination 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 prolongation and ventricular arrhythmias), which should be continued until the patient recovers completely. In case of severe extrapyramidal syndrome, anticholinergic drugs should be administered.
Side effects
Adverse reactions are classified according to frequency as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).
Blood and lymphatic system disorders
Uncommon: leukopenia.
Frequency unknown: neutropenia, agranulocytosis.
On the part of the immune system
Frequency unknown: anaphylactic reactions (urticaria, anaphylactic shock).
From the endocrine system
Common: hyperprolactinemia.
From the psyche
Common: insomnia.
Frequency unknown: confusion.
From the nervous system
Common: sedation or drowsiness; extrapyramidal syndrome, which is partially reversible with anticholinergic antiparkinsonian agents; parkinsonism; tremor; akathisia.
Uncommon: hypertonicity, dyskinesia, dystonia.
Rare: oculogyric crisis.
Tardive dyskinesia, which can occur during long-term treatment with all neuroleptics, is a condition in which antiparkinsonian drugs are ineffective and may exacerbate clinical manifestations.
Convulsions (see section "Special warnings and precautions for use").
Metabolic and nutritional disorders
Frequency unknown: hyponatremia, syndrome of inappropriate antidiuretic hormone secretion.
From the heart
Rare: ventricular arrhythmias such as torsades de pointes and ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest.
Frequency unknown: QT prolongation, sudden death (see section "Special warnings and precautions for use").
From the vascular system
Uncommon: orthostatic hypotension.
Frequency unknown: venous thromboembolism, pulmonary embolism, deep vein thrombosis, increased blood pressure (see section "Special warnings and precautions for use").
Respiratory, thoracic and mediastinal disorders
Frequency unknown: aspiration pneumonia (mainly in the case of simultaneous use of sulpiride with other drugs that depress the central nervous system).
Gastrointestinal tract
Common: constipation.
Uncommon: salivary hypersecretion.
Hepatobiliary system
Common: increased liver enzymes.
Frequency unknown: hepatocellular, cholestatic or mixed liver damage.
Musculoskeletal and connective tissue disorders
Rare: spastic torticollis, trismus.
Skin and subcutaneous tissue disorders
Common: maculopapular rash.
Conditions during pregnancy, postpartum and perinatal periods
Frequency not known: withdrawal syndrome in newborns (see section "Use during pregnancy or breastfeeding").
Reproductive system and breast disorders
Often: galactorrhea.
Uncommon: amenorrhea, impotence or frigidity.
Frequency unknown: gynecomastia.
General disorders
Common: weight gain.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Packaging
12 capsules in a blister, 2 blisters in a box.
Vacation category
According to the recipe.
Producer
Teva Operations Poland LLC.
Address
80 Mogilska Street, 31-546 Krakow, Poland.
