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Each capsule contains 50 mg of sulpiride.
Lactose monohydrate (74.43 mg) and other excipients.
Excipients/Inactive Ingredients: Lactose monohydrate, anhydrous colloidal silica, methylcellulose, talc, magnesium stearate (E-470b), titanium dioxide (E-171) and gelatin.

Pharmacotherapeutic Group: Antipsychotics: benzamides. ATC Code: N05AL 01.
Pharmacology: Pharmacodynamics: Sulpiride specifically antagonises D2 and D3 antidopaminergic receptors. In patients with psychotic symptoms that cause negative symptoms, sulpiride is effective at doses of 150 to 600 mg/day. In this dosage range, sulpiride has practically no effect on positive symptoms. Doses of 600 to 1,600 mg/day improve positive symptoms in patients with acute or chronic psychosis. Only very high doses of sulpiride induce sedative effects.
Pharmacokinetics: Absorption: After intramuscular injection of 100 mg sulpiride, peak plasma concentrations of 2.2 mg/l were reached after 30 minutes (C_max).
When taken orally, sulpiride is absorbed within 4.5 hours after administration. The C_max corresponding to one oral dose (tablet) of 200 mg varies between 0.5 and 1.8 mg/l and between 0.1 and 0.6 mg/l after the administration of one 50 mg capsule. After one dose of 50 mg oral solution the C_max was 0.28 mg/l.
Distribution: The bioavailability of the oral forms varies between 25% and 35%, with extensive inter-individual variations. Plasma levels of sulpiride are proportional to the dose.
Sulpiride is distributed rapidly to body tissues, in particular to the liver and kidneys. There is scarce distribution in the brain.
Less than 40% of the drug binds to plasma proteins. The red blood cell/plasma distribution ratio is 1.
Metabolism: Sulpiride is not actively metabolised in humans.
Elimination: Sulpiride is primarily excreted by the kidneys, by glomerular filtration. Renal clearance is usually equal to the total clearance. Ninety-two per cent (92%) of the intramuscular dose is excreted unchanged in urine.
The amount excreted in human milk has been estimated at 1/1,000 of the daily dose.
The plasma elimination half-life is 7 hours. The distribution volume at steady state is 0.94 l/kg (from 0.6 to 1.5 l/kg). The total clearance is 126 ml/min.
Toxicology: Preclinical safety data: Experimental studies in animals showed no direct or indirect evidence of teratogenic effects on embryo-foetal development, childbirth or postnatal development.
A decrease in fertility related to the pharmacological effects of the drug (effect mediated by prolactin) has been observed in animals treated with sulpiride. This effect is reversible after treatment is discontinued.

In adults: Various psychopathological symptoms (neurosis, depression, neurotic somatisation). Functional psychological disorders. Psychosomatic syndromes. Psychasthenia. Psychological old-age regression. Gastrointestinal somatisation. Vertigo.

Distribute in three doses throughout the day, and administer preferably before meals.
For the following conditions and situations the recommended doses are: Neurosis and vertigo: 150 to 300 mg/day.
Psychosis: 400 to 1,600 mg/day, although the dose can be increased to a maximum of 2,400 mg/day.
In acute and chronic psychosis, start treatment with sulpiride for injection given intramuscularly, at a rate of 2-8 ampoules/day, during the first 2 weeks.
In case of kidney failure, the dosage should be adjusted depending on creatinine clearance.
The reduction of the dose may be 35% to 70% as follows: For a clearance of 30 to 60 ml/min: administer 50% to 70% of the usual dose.
For a clearance of 10 to 30 ml/min: administer 35% to 50% of the usual dose.
For a clearance lower than 10 ml/min: administer a maximum of 35% of the usual dose.
Elderly patients may present with higher plasma concentrations of sulpiride, and so they usually require a smaller initial dose and gradual dose adjustment.
For all other indications, as a general rule, the dosage will be as follows: Adults: 3 to 6 capsules daily. In case of vertigo, it may reach 9 capsules per day.

Signs and symptoms: Experience with sulpiride in overdose is limited.
In case of overdose, dyskinetic symptoms may appear, such as spasmodic torticollis, tongue protrusion and trismus. Some patients may develop parkinsonian symptoms with life-threatening consequences and coma.
Sulpiride is partially eliminated by haemodialysis.
Treatment: There is no specific antidote for sulpiride. Treatment is only symptomatic. However, appropriate supportive measures should be taken. Close monitoring of vital signs and of heart function (risk of QT interval prolongation and subsequent ventricular arrhythmias) is recommended until the patient recovers.
In case of severe extrapyramidal symptoms, anticholinergic drugs must be administered.

Hypersensitivity to the active substance or to any of the excipients.
Concomitant prolactin-dependent tumours, for example prolactinomas of the pituitary gland and breast cancer.
Phaeochromocytoma.
Combination with levodopa (see Interactions).
Patients with QT interval prolongation (QTc > 440 msg), for example, congenital QT syndrome, or those clinical situations that pose an added risk, such as: Clinically relevant bradycardia (< 50 bpm), History of symptomatic arrhythmia, Any other clinically relevant heart disease, Concomitant treatment with class I or III antiarrhythmic agents, Concomitant treatment with any medicinal product able to prolong the QT interval (see Interactions).

QT interval prolongation: Sulpiride may induce QT interval prolongation (see Adverse Reactions). It is known that this effect may enhance the risk of serious ventricular arrhythmias such as torsade de pointes.
Before any administration, and if possible considering the patient's clinical condition, it is recommended to monitor the factors that could lead to the onset of rhythm disorders, such as: bradycardia less than 55 bpm, electrolyte imbalance; in particular hypokalaemia; congenital QT interval prolongation; concomitant treatment with medicinal products that can cause bradycardia (< 55 bpm), hypokalaemia, reduction in intracardiac conduction or QT interval prolongation (see Interactions).
Cerebrovascular accident: In randomised, placebo-controlled clinical trials conducted in elderly patients with dementia and treated with certain atypical antipsychotic drugs, it has been observed that the risk of cerebrovascular accidents triples. The increase mechanism for this risk is not known. The increased risk with other antipsychotic drugs or in other types of patient cannot be ruled out. Sulpiride should be used with caution in patients with risk factors for cerebrovascular accidents.
As with other neuroleptics, it may cause neuroleptic malignant syndrome, which is a potentially life-threatening complication characterised by hyperthermia, muscle stiffness and autonomic dysfunction. In case of hyperthermia of a non-diagnosed origin, treatment with sulpiride should be suspended (see Adverse Reactions).
It should be taken into account that Parkinson's patients may experience a worsening of the disease if sulpiride is administered concomitantly with other antidopaminergic agents. It should only be used if the neuroleptic treatment is essential (see Interactions).
The efficacy and safety of sulpiride has not been studied in depth in children. Therefore, its use is not recommended in this group of patients.
Venous thromboembolism: Cases of venous thromboembolism, sometimes fatal, have been observed with antipsychotic drugs. Therefore, sulpiride should be used with caution in patients with risk factors for thromboembolism (see Adverse Reactions).
Use in the Elderly: Elderly patients with dementia: Elderly patients with dementia-related psychosis, treated with antipsychotic drugs, have a higher risk of death. The analysis of seventeen placebo-controlled trials (with a modal duration of 10 weeks), with a large proportion of patients taking atypical antipsychotic drugs, revealed a risk of death in patients treated with medicinal products between 1.6 and 1.7 times the risk of death in patients treated with placebo. In the course of a typical 10-week controlled trial, the death rate in patients treated with a medicinal product was approximately 4.5% compared with approximately 2.6% in the placebo group. Although the causes of death in clinical trials with atypical antipsychotic drugs vary, it appears that the majority of deaths were cardiovascular (e.g. heart failure, sudden death) or infectious (e. g. pneumonia) in nature. Similar to treatment with atypical antipsychotic drugs, as observational studies suggest, treatment with conventional antipsychotic drugs may increase mortality.
It is not clear whether the increased mortality results in observational studies may be attributed to antipsychotic drugs or to some of the patient characteristics.

If there are reports of hyperglycaemia in patients treated with atypical antipsychotic agents, the blood glucose of patients with diagnosed diabetes mellitus or with risk factors for having diabetes, who have started treatment with sulpiride, should be appropriately monitored.
Neuroleptics, including sulpiride, may reduce the seizure threshold, and some cases of seizures have been reported with sulpiride (see Adverse Reactions). Therefore patients with epilepsy or with a history of seizures should be strictly monitored during treatment with sulpiride.
Sulpiride is eliminated via the kidneys. In case of kidney failure, the dose should be reduced (see Dosage & Administration).
Like other neuroleptics, sulpiride should be used with caution in elderly patients since they may be at a higher risk of developing orthostatic hypotension, sedation and extrapyramidal disorders such as tardive dyskinesia. Observation is recommended during treatment to detect early signs of tardive dyskinesia, and reduce or discontinue treatment to prevent a more serious manifestation of the symptom. It is also advisable to monitor heart function.
Elderly patients may need a lower starting dose and a gradual adjustment of the dose (see Dosage & Administration).
In patients with aggressive behaviour or who are impetuously agitated, sulpiride can be administered with a sedative.
Warning about excipients: This medicinal product contains lactose. Patients with hereditary galactose intolerance, Lapp lactase deficiency (deficiency observed in some parts of Lapland) or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Even when used in accordance with recommendations, sulpiride may cause sedation, and the ability to drive or operate machines may be affected (see Adverse Reactions).

Fertility and pregnancy: A decrease in fertility related to the pharmacological effects of the product (effect mediated by prolactin) has been observed in animals treated with sulpiride.
Animal studies do not suggest direct or indirect harmful effects with respect to pregnancy, embryo/foetal development and/or postnatal development.
In humans, there are limited clinical data in pregnant women treated with sulpiride. In most cases of foetal and neonatal disorders reported during treatment with sulpiride during pregnancy, alternative explanations could be suggested which seem more likely.
Therefore, due to limited experience sulpiride is not recommended during pregnancy.
If sulpiride is used during pregnancy, appropriate monitoring of the newborn should be considered to monitor the safety profile of sulpiride.
Newborns who have been exposed to antipsychotic medicines (including sulpiride) during the third trimester of pregnancy may present with extrapyramidal side effects and/or withdrawal symptoms that may vary in severity and duration after birth, and therefore close monitoring is advised. Cases of agitation, hypertonia, hypotonia, tremor, drowsiness, difficulty breathing and eating disorders have been reported.
Breast-feeding: Sulpiride is excreted in human milk. Therefore, breast-feeding is not recommended during treatment with sulpiride.

Based on experience with sulpiride, the following undesirable effects are listed in groups according to the MedDRA system organ class, with some adaptations.
Adverse reactions associated with sulpiride are: Cardiac disorders: Postural hypotension.
QT interval prolongation and ventricular arrhythmias, such as torsade de pointes, ventricular tachycardia, which can cause ventricular fibrillation or cardiac arrest, sudden death (see Warnings).
Endocrine disorders: Hyperprolactinaemia.
General disorders and administration site conditions: Like all neuroleptics, malignant syndrome is a potentially life-threatening complication (see Warnings).
Weight gain.
Hepatobiliary disorders: Increase in liver enzymes.
Nervous system disorders: Sedation or drowsiness.
Extrapyramidal symptoms and related disorders: parkinsonism and associated symptoms: tremor, hypertonia, hypokinesia, hypersalivation; acute dyskinesia and dystonia (spasmodic torticollis, oculogyric crises, trismus); akathisia.
These symptoms are generally reversible if anti-Parkinson's medication is administered: Tardive dyskinesia (characterised by involuntary and rhythmic movements mainly of the tongue and/or face), typical of all neuroleptics, after administration for more than 3 months. The anti-Parkinson's medication is ineffective or may exacerbate symptoms.
Seizures (see Precautions).
Reproductive system and breast disorders: Disorders related to hyperprolactinaemia: Galactorrhoea, amenorrhoea, gynaecomastia, increased chest, chest pain, orgasmic dysfunction, erectile dysfunction.
Skin and subcutaneous tissue disorders: Maculopapular rash.
Vascular disorders: Venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see Warnings).
Pregnancy, puerperium and perinatal conditions: Unknown frequency: Neonatal withdrawal syndrome (see Use in Pregnancy & Lactation).

Contraindicated combinations: Levodopa: reciprocal antagonism between levodopa and neuroleptics (see Contraindications).
Consumption of grapefruit juice during treatment with sulpiride.
Combinations not recommended: Alcohol: alcohol can enhance the sedative effects of neuroleptics. The consumption of alcoholic beverages and medicinal products containing alcohol should be avoided.
Combination with medicinal products that may prolong the QT interval or induce torsade de pointes (see Warnings).
Drugs that induce bradycardia such as beta blockers, calcium channel blockers, inducers of bradycardia such as diltiazem and verapamil, clonidine, guanfacine; digitalis.
Medicinal products that induce hypokalaemia: hypokalaemic diuretics, laxatives, amphotericin B (IV), glucocorticoids, tetracosactide. Hypokalaemia should be corrected.
Class IA antiarrhythmic drugs such as quinidine, disopyramide.
Class III antiarrhythmic drugs such as amiodarone, sotalol.
Other medicinal products such as pimozide, sultopride, haloperidol, thioridazine, methadone, imipramine, lithium, bepridil, cisapride, erythromycin (IV), vincamine (IV), halofantrine, pentamidine, sparfloxacin.
Combinations to be taken into account: Sucralfate: Concomitant administration of sulpiride with sucralfate may reduce plasma levels of sulpiride and may lead to a reduction or loss of therapeutic action. Therefore, sulpiride should be administered at least two hours before the sucralfate.
Antacids: The joint administration of sulpiride with antacids containing magnesium or aluminium salts may cause a decrease in the plasma levels of sulpiride, which may lead to a reduction or loss of therapeutic action. Therefore, sulpiride should be administered at least two hours before antacids.
Antihypertensive agents: antihypertensive effect and possibility of increased occurrence of postural hypotension (additive effect).
CNS depressants: including narcotics, analgesics, sedative H1 antihistamines, barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives.

Incompatibilities: Not applicable.
Special precautions for disposal and other handling: No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.

Store below 30°C.
Shelf life: 24 months.

Antipsychotics / Anxiolytics

N05AL01 - sulpiride ; Belongs to the class of benzamides antipsychotics.