Short-term treatment of states of agitation and aggressiveness in patients with acute and chronic psychotic disorders (schizophrenia, chronic non-schizophrenic delusions: paranoid delusions, chronic hallucinatory psychosis).

Intramuscular injection use.
For use in adults only.
The minimum effective dose should always be used. If the patient’s clinical condition allows, treatment should be initiated at a low dose, then gradual dosage titration may be used.
The dose is 400 to 800 mg per day for 2 weeks.

This drug is contraindicated in the following situations: • hypersensitivity to sulpiride or to one of the other ingredients of the drug, • prolactin-dependent tumors (e.g. pituitary gland prolactinomas and breast cancer), • known or suspected pheochromocytoma, • in combination with: o non-antiparkinsonian dopamine agonists (cabergoline and quinagolide). (see Section 4.5)

Warnings
* Potentially fatal neuroleptic malignant syndrome: If unexplained fever occurs, treatment must imperatively be discontinued since this may be one of the symptoms of the malignant syndrome reported with neuroleptic drugs (pallor, hyperthermia, autonomic disorders, consciousness disorders, muscle rigidity).
Signs of autonomic dysfunction, such as perspiration and changes in arterial blood pressure, may occur before hyperthermia and thus constitute early warning signs.
Although this effect of neuroleptics may be idiosyncratic in origin, there may be predisposing risk factors, such as dehydration and organic brain damage.
* Prolonged QT interval: sulpiride can cause dose-dependent prolongation of the QT interval. This effect, which is known to increase the risk of serious ventricular arrhythmias, particularly torsades de pointes, is enhanced in patients with bradycardia, hypokalemia, and congenital or acquired QT prolongation (when sulpiride is taken with a medicinal product prolonging the QT interval) (see Section 4.8).
Consequently, before administering the drug, and if the clinical situation permits, patients should be checked for the following risk factors that may promote this type of arrhythmia:
• bradycardia of less than 55 beats per minute,

• hypokalemia,
• congenital QT interval prolongation,
• ongoing treatment with a drug likely to induce marked bradycardia (less than 55 beats per minute), hypokalemia, delayed intracardiac conduction or QT interval prolongation (see Sections 4.3 and 4.5).
Except in emergencies, it is recommended that an ECG be performed as part of the initial evaluation of patients due to receive treatment with a neuroleptic agent.
Stroke
In randomized, placebo-controlled clinical trials in elderly patients with dementia and treated with atypical antipsychotics, a higher risk of stroke was observed versus placebo. The reason for this increased risk is unknown. Increased risk with other antipsychotics or in other patient populations cannot be ruled out. This drug should be used with caution in patients with risk factors for stroke.
Elderly patients with dementia
The risk of mortality increases in elderly patients suffering from dementia-related psychosis and treated with antipsychotic drugs.
Analysis of 17 placebo-controlled studies (mean duration of 10 weeks), conducted in patients mainly taking atypical antipsychotic drugs, showed that the risk of mortality increased 1.6- to 1.7-fold in patients treated with these medicinal products versus placebo.
After a mean treatment period of 10 weeks, the risk of mortality was 4.5% in the treated patient group versus 2.6% in the placebo group.
Although the causes of death varied in the clinical trials with the atypical antipsychotic drugs, the majority of deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia).
Epidemiological studies suggest that treatment with conventional antipsychotic drugs may increase mortality, as is the case for atypical antipsychotic drugs.
The respective contribution of the antipsychotic drug and patient characteristics to the increase in mortality found in the epidemiological studies is unclear.
* Venous thromboembolism: cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotic drugs often present acquired risk factors for VTE, any potential risk factors for VTE must be identified before and during treatment with Dogmatil and preventive measures should be taken (see Section 4.8).
Administration of this medicinal product is not recommended with alcohol, levodopa, antiparkinsonian dopamine agonists, antiparasitic agents likely to induce torsades de pointes, methadone, other neuroleptics and medicinal products likely to induce torsades de pointes (see Section 4.5).
This medicinal product contains sodium. The sodium content is 30 mg per dose. This should be taken into account in patients on a strict low-sodium diet.
Special precautions for use
In patients with diabetes or with risk factors for diabetes who are starting treatment with sulpiride, appropriate blood glucose monitoring should be carried out.
Except in special cases, this drug should not be administered to patients with Parkinson's disease.
In patients with renal insufficiency, reduce the dosage and increase monitoring; in the event of serious renal insufficiency, intermittent treatment courses are recommended.
Monitoring of treatment with sulpiride must be intensified in:
• epileptic patients, as sulpiride may lower the seizure threshold; cases of seizure have been reported in patients treated with sulpiride (see Section 4.8),
• elderly patients with greater susceptibility to postural hypotension, sedation and extrapyramidal effects.

Sedatives
It must be taken into account that many drugs or substances can have additive depressant effects on the central nervous system and contribute to a decrease in alertness. These drugs include morphine derivatives (analgesics, antitussives, and replacement therapies), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline,

doxepin, mianserin, mirtazapine, trimipramine), sedative H
1-antihistamines, centrally-acting antihypertensives, baclofen, and thalidomide.
Drugs likely to induce torsades de pointes
This serious cardiac rhythm disorder can be caused by a number of medicinal products, anti-arrhythmics or not. Hypokalemia (see Potassium-depleting drugs) is a promoting factor, as is bradycardia (see Bradycardia-inducing drugs) or preexisting congenital or acquired QT interval prolongation.
The medicines involved are in particular class Ia and III antiarrhythmics and certain neuroleptics.
For erythromycin, spiramycin and vincamine, only intravenously administered dosage forms are concerned by this interaction.
Coadministration of two torsadogenic drugs is generally contraindicated.
However, methadone, as well as certain sub-classes, are exceptions:
• antiparasitics (halofantrine, lumefantrine, pentamidine) are merely not recommended in combination with other torsadogenic drugs;
• neuroleptics likely to induce torsades de pointes are also not recommended, but not contraindicated, in combination with other torsadogenic drugs.
Contraindicated combinations (see Section 4.3)
+ Non-antiparkinsonian dopamine agonists (cabergoline, quinagolide)
Mutual antagonism between dopamine agonists and neuroleptics.
Inadvisable combinations (see Section 4.4)
+ Antiparasitic agents likely to induce torsades de pointes (halofantrine, lumefantrine, pentamidine)
Increased risk of ventricular arrhythmias, particularly torsades de pointes.
If possible, treatment with the azole antifungal agent should be discontinued.
If coadministration cannot be avoided, QT interval should be checked before treatment and the ECG monitored.
+ Antiparkinsonian dopamine agonists (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline)
Mutual antagonism between dopamine agonists and neuroleptics.
Dopamine agonists can cause or worsen psychotic disorders. If treatment with neuroleptics is required in patients with Parkinson's disease treated with dopamine agonists, these dopamine agents should be tapered off gradually (sudden discontinuation exposes the patient to a risk of neuroleptic malignant syndrome).
+ Other drugs likely to induce torsades de pointes: class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide) and class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide), and other drugs such as bepridil, cisapride, diphemanil, erythromycin IV, mizolastine, vincamine IV, moxifloxacin, spiramycin IV
Increased risk of ventricular arrhythmias, particularly torsades de pointes.
+ Other neuroleptics likely to induce torsades de pointes (amisulpride, chlorpromazine, cyamemazine, droperidol, haloperidol, levomepromazine, pimozide, pipothiazine, sertindole, sulpiride, sultopride, tiapride, veralipride)
Increased risk of ventricular arrhythmias, particularly torsades de pointes.
+ Alcohol
Potentiation of the sedative effects induced by neuroleptic drugs.
Impaired alertness may make driving vehicles and using machines dangerous.
Patients should avoid consuming alcoholic beverages or medicines containing alcohol.
+ Levodopa
Mutual antagonism between levodopa and neuroleptics.
In patients with Parkinson’s disease, minimum effective doses of each of these drugs should be used.
+ Methadone
Increased risk of ventricular arrhythmias, especially torsades de pointes
Combinations requiring precautions for use
+ Beta-blockers in heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)
Increased risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and ECG monitoring required.

+ Bradycardia-inducing drugs (in particular class Ia antiarrhythmics, beta blockers, certain class III antiarrhythmics, certain calcium channel blockers, digitalis glycosides, pilocarpine, anticholinesterases)
Increased risk of ventricular arrhythmias, particularly torsades de pointes.
Clinical and ECG monitoring required.
+ Potassium-depleting drugs (potassium-depleting diuretics, alone or in combination, stimulant laxatives, glucocorticoids, tetracosactide and amphotericin B IV)
Increased risk of ventricular arrhythmias, particularly torsades de pointes.
Any existing hypokalemia should be corrected before administration, and clinical, electrolyte and ECG monitoring performed.
Combinations to be taken into account
+ Antihypertensives
Increased risk of hypotension, particularly postural.
+ Beta blockers (except esmolol and sotalol and beta blockers used in heart failure)
Vasodilator effect and risk of hypotension, particularly postural (additive effect).
+ Nitrates, nitrites and related drugs
Increased risk of hypotension, particularly postural.

Pregnancy
Good mental health should preferably be maintained throughout pregnancy to avoid decompensation. If drug therapy is necessary in order to ensure this mental wellbeing, it must be instituted or continued at an effective dose throughout pregnancy.
Analysis of exposed pregnancies has not revealed any particular teratogenic effect with sulpiride.
Injectable neuroleptics used in emergency situations can cause hypotension in the mother.
Although no cases have been described in neonates, sulpiride could theoretically cause the following signs if continued to the end of pregnancy, particularly at high doses:
• signs related to its atropine-like properties, exacerbated if combined with antiparkinsonian agents: tachycardia, hyperexcitability, abdominal distension, delayed meconium excretion,
• extrapyramidal signs: hypertonia, tremor,
• sedation.
Consequently, the use of sulpiride may be considered at any stage of pregnancy. The above effects should be taken into account when monitoring the neonate.
Lactation
As sulpiride is excreted in breast-milk, breast-feeding is not recommended during treatment.

The attention of patients, particularly those who drive or use machines, should be drawn to the risk of drowsiness associated with the use of this medicinal product (see Section 4.8).

Nervous system disorders:
• early-onset dyskinesia (spasmodic torticollis, oculogyric crises, trismus) reversible following
administration of an anticholinergic antiparkinsonian agent,
• extrapyramidal syndrome:
o akinetic symptoms with or without hypertonia, partially resolving with anticholinergic antiparkinsonian agents,
o hyperkinetic-hypertonic, excitatory motor activity,
o akathisia,
• tardive dyskinesia, characterized by involuntary rhythmic movements particularly of the tongue and/or face, have been observed, as is the case with all neuroleptics during prolonged treatment: anticholinergic antiparkinsonians have no effect or may cause exacerbation,

• sedation or drowsiness,
• seizures (see Section 4.4),
• potentially fatal neuroleptic malignant syndrome (see Section 4.4).
Endocrine disorders
• transient hyperprolactinemia, reversible on treatment discontinuation, possibly inducing amenorrhea, galactorrhea, gynecomastia, impotence or frigidity.
Metabolism and nutrition disorders:
• weight gain.
Cardiac disorders:
• QT interval prolongation,
• ventricular arrhythmias such as torsades de pointes and ventricular tachycardia, which can lead to ventricular fibrillation or cardiac arrest,
• sudden death (see Section 4.4).
Vascular disorders
• postural hypotension,
• cases of venous thromboembolism, including cases of pulmonary embolism and deep vein thrombosis, have been reported with antipsychotic drugs - unknown frequency (see Section 4.4).
Hepatobiliary disorders
• increase in hepatic enzymes.
Skin and subcutaneous tissue disorders
• maculopapular rash.

Experience with sulpiride overdose is limited. Dyskinesia with spasmodic torticollis, protrusion of the tongue and trismus may occur. Certain patients may develop potentially life-threatening Parkinsonian syndrome or even coma.
Sulpiride is partly eliminated by hemodialysis.
There is no specific antidote to sulpiride.
Symptomatic treatment, resuscitation under strict continuous cardiac and respiratory monitoring (risk of QT interval prolongation and ventricular arrhythmias), which should be maintained until the patient recovers.
If severe extrapyramidal syndrome develops, an anticholinergic agent must be administered.

NEUROLEPTIC ANTIPSYCHOTIC
BENZAMIDE
ATC Code: N05AL01
Sulpiride interferes in cerebral dopaminergic nerve transmission and exerts an activating action simulating a dopaminomimetic effect at low doses. At higher doses, sulpiride also has an antiproductive action.

* Following intramuscular injection of a 100 mg dose, peak sulpiride plasma concentrations are reached in 30 minutes, corresponding to 2.2 mg/l.
* Sulpiride is rapidly distributed into tissue: the apparent volume of distribution at steady state is 0.94 l/kg.
Plasma protein binding is approximately 40%.
Sulpiride is excreted in breast milk to a limited extent, and crosses the placental barrier.
* Sulpiride undergoes slight metabolism in man; 92% of the sulpiride dose administered via the intramuscular route is recovered as the parent drug in the urine.
* Sulpiride mainly undergoes renal excretion, by glomerular filtration.
Total clearance is 126 ml/min. The plasma elimination half-life is 7 hours.

Not applicable.

Not applicable.

Not applicable.

Not Specified

Not applicable.

Not applicable.

Not applicable.