DOGMATIL 50 mg Gél Plq/30

Capsule.
Box of 30, blister packs.

For one capsule:

Sulpiride base: 50,00 mg

Excipient with known effect: this medicine contains 66,92 mg of lactose monohydrate per tablet.

Excipients:

• Short-term symptomatic treatment of anxiety in adults when usual therapies have failed.
• Severe behavioural disorders (agitation, self-mutilation, stereotypies) in children over 6 years of age, particularly in the context of autistic syndromes.

Dosage

The minimum effective dose should always be sought. If the patient's clinical condition allows, treatment will be started at a low dose, then gradually increased in steps.

In adults

Short-term symptomatic treatment of anxiety in adults in case of failure of usual therapies:

The daily dose is 50 to 150 mg for a maximum of 4 weeks.

Paediatric population

In children over 6 years of age:

Severe behavioural disorders (agitation, self-injury, stereotypies), in particular in the context of autistic syndromes:

The daily dose is 5 to 10 mg/kg.

In children, the oral solution form is better suited.

Method of administration

Oral use.

This medicine must never be used in the following situations:

• hypersensitivity to the active substance or to any of the excipients mentioned in section Composition,
• prolactin-dependent tumours (for example prolactin-secreting pituitary adenoma and breast cancer),
• known or suspected pheochromocytoma,
• in association with:
  • dopaminergic agents not used for Parkinson's disease (cabergoline, quinagolide),
  • citalopram, escitalopram, hydroxyzine, domperidone and piperaquine (see section Interactions),
• acute porphyria.

Special warnings

Potentially fatal neuroleptic malignant syndrome:

A potentially fatal neuroleptic malignant syndrome, reported in association with antipsychotics, is characterised by hyperthermia, pallor, autonomic disorders, impaired consciousness, muscular rigidity, rhabdomyolysis, elevated serum creatine phosphokinase levels and dysautonomia. Cases with atypical features such as hyperthermia without muscular rigidity or hypertonia have been observed. In the case of hyperthermia of undiagnosed origin, which may be considered a precursor sign/symptom of neuroleptic malignant syndrome or as an atypical neuroleptic malignant syndrome, any treatment with sulpiride and all other antipsychotic medicines must be promptly discontinued under medical supervision.
Signs of autonomic dysfunction, such as sweating and arterial instability, may precede the onset of hyperthermia and therefore constitute early warning signs. Although this effect of neuroleptics may have an idiosyncratic origin, certain risk factors appear to predispose to it, such as dehydration or organic brain damage.

QT interval prolongation:

Sulpiride prolongs the QT interval in a dose-dependent manner. This effect, known to potentiate the risk of occurrence of serious ventricular arrhythmias, notably of the torsades de pointes type, is increased by the presence of bradycardia, hypokalaemia, congenital or acquired long QT (association with a medicinal product increasing the QT interval) (see section Adverse effects).

Therefore, when the clinical situation permits, it is advisable to ensure, before any administration, the absence of factors that may favour the occurrence of this cardiac rhythm disorder:

• bradycardia below 55 beats per minute,
• hypokalaemia,
• congenital prolongation of the QT interval,
• current treatment with a medicinal product likely to cause marked bradycardia (< 55 beats per minute), hypokalaemia, slowing of intracardiac conduction, prolongation of the QT interval (see sections Contraindications and Interactions).

Apart from emergency situations, it is recommended to perform an electrocardiogram (ECG) as part of the initial assessment of patients to be treated with a neuroleptic.

Cerebrovascular accident:

In randomised placebo-controlled clinical studies conducted in elderly patients with dementia treated with certain atypical antipsychotics, a higher risk of cerebrovascular accident compared with placebo was observed. The mechanism of such an increased risk is not known. An increased risk with other antipsychotics or in other patient populations cannot be excluded. This medicinal product should be used with caution in patients with risk factors for cerebrovascular accident.

Elderly patients with dementia:

The risk of mortality is increased in elderly patients with dementia-related psychosis treated with antipsychotics.

Analyses of 17 controlled studies versus placebo (mean duration of 10 weeks), carried out in patients mostly taking atypical antipsychotics, revealed a mortality risk 1,6 to 1,7 times higher in patients treated with these medicinal products compared with placebo.

At the end of treatment with a mean duration of 10 weeks, the mortality risk was 4,5% in the treated patient group compared with 2,6% in the placebo group.

Although the causes of death in clinical trials with atypical antipsychotics were varied, most of these deaths appeared to be either of cardiovascular origin (for example cardiac failure, sudden death) or of infectious origin (for example pneumonia).

Epidemiological studies suggest that, as with atypical antipsychotics, treatment with conventional antipsychotics may increase mortality.

The respective contribution of the antipsychotic and of patient characteristics to the increased mortality in epidemiological studies is not clear.

Venous thromboembolism:

Cases of venous thromboembolism (VTE) have been reported with antipsychotics. Patients treated with antipsychotics often present acquired risk factors for VTE; any potential risk factor for VTE must be identified before and during treatment with DOGMATIL and preventive measures must be implemented (see section Adverse effects).

Breast cancer :

Sulpiride may increase prolactin levels. It should therefore be used with caution. Regardless of sex, patients with a personal or family history of breast cancer must be closely monitored during treatment with sulpiride.

Decreased intestinal peristalsis:

Cases of intestinal obstruction have been reported in patients treated with antipsychotics. Rare cases of ischaemic colitis and intestinal necrosis, sometimes fatal in outcome, have also been reported. The majority of these patients were concomitantly treated with one or more medicinal products inducing a decrease in intestinal motility (in particular medicinal products with anticholinergic properties). The onset of abdominal pain with vomiting and/or diarrhoea should draw attention. It is imperative that constipation be recognised and actively treated. The occurrence of ileus/intestinal obstruction should require emergency management.

Other warnings:

The use of this medicinal product is not recommended in combination with alcohol, levodopa, dopaminergic antiparkinsonian agents, antiparasitic agents liable to cause torsade de pointes, methadone, other neuroleptics and medicinal products liable to cause torsade de pointes (see section Interactions).

The risk of onset of tardive dyskinesia must be taken into account, even at low doses, particularly in elderly subjects.

In children, as efficacy and tolerability have not been fully studied, precautions should be taken when using sulpiride (see section Dosage and administration). Given the cognitive impact, an annual clinical examination assessing learning capacity is recommended. The dosage will be regularly adjusted according to the clinical condition of the child.

Taking tablets or capsules is contraindicated in children under 6 years of age because it may cause aspiration.

Precautions for use

Diabetic patients and patients with risk factors for diabetes who start treatment with sulpiride must undergo appropriate blood glucose monitoring.

Outside exceptional situations, this medicine should not be used in cases of Parkinson's disease.

In cases of renal impairment, reduce the dose and increase monitoring; in cases of severe renal impairment, it is recommended to prescribe intermittent courses of treatment.

Monitoring of treatment with sulpiride must be strengthened:

• in epileptic subjects due to the possibility of lowering the epileptogenic threshold, cases of convulsions have been reported in patients treated with sulpiride (see section Adverse effects),
• in elderly subjects who show greater sensitivity to orthostatic hypotension, sedation, and extrapyramidal effects.

Cases of leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics including DOGMATIL. Unexplained infections or unexplained fever may be indicative of leukopenia (see section Adverse effects) and may require immediate blood tests.

DOGMATIL must be used with caution in patients with a history of glaucoma, ileus, congenital digestive stenosis, urinary retention or prostatic hyperplasia.

DOGMATIL must be used with caution in hypertensive patients, and particularly in elderly subjects, due to the risk of hypertensive crisis. Appropriate monitoring must be put in place for these patients.

Excipients with known effect

This medicine contains lactose. Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases) must not take this medicine.

+ Sedative medicinal products

It must be taken into account that many medicinal products or substances may add together their central nervous system depressant effects and contribute to reducing alertness. These include morphine derivatives (analgesics, antitussives and substitution treatments), neuroleptics, barbiturates, benzodiazepines, anxiolytics other than benzodiazepines (for example, meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedating H1 antihistamines, centrally acting antihypertensives, baclofen and thalidomide.

+ Medicinal products causing orthostatic hypotension

Besides antihypertensives, many medicines may cause orthostatic hypotension. This is notably the case for nitrates, phosphodiesterase type 5 inhibitors, alpha-blockers used in urology, imipramine-like antidepressants and phenothiazine neuroleptics, dopamine agonists and levodopa. Their concomitant use therefore risks increasing the frequency and intensity of this undesirable effect. Refer to the interactions specific to each class, with the corresponding levels of constraint.

+ Medicines likely to cause torsades de pointes

This serious heart rhythm disorder may be provoked by a number of medicinal products, whether antiarrhythmic or not. Hypokalemia (see Hypokalemic agents) is a predisposing factor, as is bradycardia (see Bradycardic agents) or a pre-existing prolongation of the QT interval, congenital or acquired.

The medicinal products responsible for this undesirable effect include in particular class Ia and III antiarrhythmics, and certain neuroleptics. Other molecules not belonging to these classes are also implicated.

For erythromycin and vincamine, only the intravenous forms are concerned by this interaction.

The use of a torsadogenic medicine with another torsadogenic medicine is generally contraindicated.

Some of them, because of their unavoidable nature, are an exception to the rule, being only advised against with other torsadogenic agents. These are antiparasitic agents (chloroquine, halofantrine, lumefantrine, pentamidine), arsenic trioxide, hydroxychloroquine, methadone, crizotinib, cotrimoxazole and neuroleptics.

Note that citalopram, escitalopram, domperidone, hydroxyzine and piperaquine do not follow this relaxation and are contraindicated with all torsadogenic agents, following a European arbitration.

Contraindicated combinations

+ Citalopram, escitalopram

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

+ Dopaminergics outside Parkinson's disease (for example cabergoline, quinagolide)

Reciprocal antagonism between the dopamine agonist and neuroleptics.

+ Domperidone

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

+ Hydroxyzine

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

+ Piperaquine

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Combinations not recommended

+ Antiparasitics that may cause torsades de pointes (for example chloroquine, halofantrine, lumefantrine, pentamidine)

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

If possible, stop one of the two treatments.

If the association cannot be avoided, check the QT interval beforehand and monitor with continuous ECG.

+ Dopaminergic antiparkinsonian agents (for example amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, rasagiline, ropinirole, rotigotine, selegiline)

Reciprocal antagonism between dopaminergic agents and neuroleptics.

The dopaminergic agent may cause or worsen psychotic disorders. If neuroleptic treatment is necessary in a parkinsonian patient treated with dopaminergic agents, the latter must be gradually reduced until discontinued (abrupt discontinuation exposes the patient to a risk of "neuroleptic malignant syndrome").

+ Other substances likely to cause torsades de pointe (except antiparasitic agents, neuroleptics, citalopram, domperidone, escitalopram, hydroxyzine, piperaquine and methadone): class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (amiodarone, dronedarone, sotalol), and other substances such as, but not limited to, arsenic trioxide, cocaine, crizotinib, domperidone, erythromycin IV, hydroxychloroquine, levofloxacin, mequitazine, moxifloxacin, spiramycin IV, toremifene, vandetanib, vincamine IV.

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

If the combination cannot be avoided, regular clinical and electrocardiographic monitoring.

+ Other neuroleptics liable to cause torsades de pointes (amisulpride, chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipotiazine, sulpiride, tiapride, zuclopenthixol)

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

If the combination cannot be avoided, regular clinical and electrocardiographic monitoring.

+ Alcohol (beverage or excipient)

Alcohol increases the sedative effect of these substances.

Impaired alertness may make driving vehicles and using machines dangerous.

Avoid taking alcoholic beverages and medicines containing alcohol.

+ Delamanid

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

If the combination cannot be avoided, regular clinical and electrocardiographic monitoring.

+ Levodopa

Reciprocal antagonism of levodopa and neuroleptics.

In parkinsonian patients, use the minimum effective doses of each of the two medicines.

+ Methadone

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

+ Sodium oxybate

Increased central depression. Impaired alertness may make driving vehicles and using machines dangerous.

+ Sulfamethoxazole + trimethoprim

Risk of ventricular arrhythmias, in particular torsades de pointes.

If the combination cannot be avoided, regular clinical and electrocardiographic monitoring.

Associations requiring precautions for use

+ Anagrelide

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Azithromycin

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Beta-blockers in heart failure (for example bisoprolol, carvedilol, metoprolol, nebivolol)

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring.

+ Bradycardic agents (notably class Ia antiarrhythmics, beta-blockers, certain class III antiarrhythmics, certain calcium antagonists, digoxin, digitalis, pasireotide, pilocarpine, anticholinesterases,...)

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Ciprofloxacin, levofloxacin, norfloxacin

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Clarithromycin, roxithromycin

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Glasdegib

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Hypokalaemic agents (for example hypokalaemic diuretics, alone or in combination, stimulant laxatives, glucocorticoids, tetracosactide and intravenous amphotericin B,...).

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Correct any hypokalaemia before administering the product and carry out clinical, electrolyte and electrocardiographic monitoring.

+ Lithium

Risk of onset of neuropsychiatric signs suggestive of neuroleptic malignant syndrome or of lithium intoxication.

Regular clinical and biological monitoring, particularly at the start of the combination.

+ Medicines causing male hypogonadism

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Ondansetron

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Sucralfate

Decreased digestive absorption of sulpiride.

Take sucralfate apart from sulpiride (at least 2 hours apart, if possible).

+ Gastrointestinal topicals, antacids and adsorbents

Decreased digestive absorption of sulpiride.

As a precaution, these topicals or antacids should be taken at a distance from any other medication (more than 2 hours, if possible).

Associations to be taken into account

+ Aripiprazole

Risk of reduced efficacy, notably of aripiprazole, following dopaminergic receptor antagonism by the neuroleptic.

+ Other sedative medicines

Increased central depression.

Impaired alertness may make driving vehicles and using machines dangerous.

+ Beta-blockers in heart failure (for example bisoprolol, carvedilol, metoprolol, nebivolol)

(For beta-blockers used in heart failure, see also "Associations requiring precautions for use")

Vasodilating effect and risk of hypotension, particularly orthostatic (additive effect).

+ Dapoxetine

Risk of increased adverse effects, notably dizziness or syncope.

+ Orlistat

Risk of therapeutic failure in case of concomitant treatment with orlistat.

+ Medicines lowering blood pressure

Risk of increased hypotension, in particular orthostatic hypotension.

Pregnancy

Data on the use of sulpiride in pregnant women are very limited. The safety of use of sulpiride during pregnancy has not been established.

Sulpiride crosses the placenta. Studies in animals have shown toxicity to the reproductive function

The use of sulpiride is not recommended during pregnancy and in women of childbearing potential not using effective contraception, unless the expected benefits justify the potential risks.

Newborns exposed to antipsychotics (including DOGMATIL) during the third trimester of pregnancy present a risk of adverse events including extrapyramidal symptoms and/or withdrawal symptoms, which may vary in severity and duration after birth (see section Adverse effects). The following reactions have been reported: agitation, hypertonia, hypotonia, tremors, somnolence, respiratory distress, feeding disorders. Consequently, newborns must be closely monitored.

Breast-feeding

Sulpiride is excreted into breast milk in fairly significant quantities, in some cases exceeding the accepted value of 10 % of the maternal weight-adjusted dose, but blood concentrations in breastfed infants have not been evaluated. Information on the effects of sulpiride in newborns/infants is insufficient.

A decision must be made to either discontinue breastfeeding or not take sulpiride, taking into account the benefit of breastfeeding for the child and the benefit of the treatment for the woman.

Fertility

A decrease in fertility related to the pharmacological effects of the medicine (prolactin-dependent effect) has been observed in treated animals.

Attention is drawn, particularly to vehicle drivers and machine operators, to the risks of drowsiness associated with the use of this medicine (see section Adverse effects).

Blood and lymphatic system disorders (see section Warnings and precautions)

Uncommon: leukopenia.

Frequency not known: neutropenia and agranulocytosis.

Immune system disorders

Frequency not known: anaphylactic reaction: urticaria, anaphylactic shock.

Endocrine disorders

Common: hyperprolactinemia.

Metabolism and nutrition disorders

Frequency not known : hyponatremia, syndrome of inappropriate antidiuretic hormone secretion.

Psychiatric disorders

Common: insomnia.

Frequency not known: confusion.

Nervous system disorders

Common:

• sedation or drowsiness,
• extrapyramidal syndrome partially responding to anticholinergic antiparkinsonian agents,
• parkinsonism,
• tremors,
• akathisia.

Uncommon: hypertonia, dyskinesia, dystonia.

Rare: oculogyric crises.

Frequency not known:

• potentially fatal neuroleptic malignant syndrome (see section Warnings and precautions),
• hypokinesia,
• tardive dyskinesias have been observed as with all neuroleptics during prolonged treatment: anticholinergic antiparkinsonian agents have no effect or may cause worsening,
• convulsions (see section Warnings and precautions).

Cardiac disorders

Rare: ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, which may lead to ventricular fibrillation or cardiac arrest.

Frequency not known: prolongation of the QT interval, sudden death (see section Warnings and precautions).

Vascular disorders

Uncommon: orthostatic hypotension.

Frequency not known: venous embolism, pulmonary embolism, deep vein thrombosis (see section Warnings and precautions), increased blood pressure (see section Warnings and precautions).

Respiratory, thoracic and mediastinal disorders

Frequency not known: aspiration pneumonia (mainly in association with other CNS depressant medicines).

Gastrointestinal disorders

Common: constipation.

Uncommon: hypersalivation.

Hepatobiliary disorders

Common: increased liver enzymes.

Frequency not known: hepatocellular, cholestatic or mixed injuries.

Skin and subcutaneous tissue disorders

Common: maculopapular rash.

Musculoskeletal and connective tissue disorders

Frequency not known : rhabdomyolysis.

Pregnancy, puerperal and perinatal conditions

Frequency not known: neonatal withdrawal syndrome (see section Fertility, pregnancy and breastfeeding).

Disorders of the reproductive system and breast

Common: galactorrhoea.

Uncommon: amenorrhoea, impotence or frigidity.

Frequency not known: gynaecomastia.

General disorders and administration site conditions

Common: weight gain.

Frequency not known : hyperthermia (see section Warnings and precautions).

Investigations

Frequency not known: increase in the blood level of creatine phosphokinase.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.

Experience with sulpiride in cases of overdose is limited. Dyskinesias with spasmodic torticollis, protrusion of the tongue and trismus may appear. Some patients may develop a parkinsonian syndrome that can be life-threatening, or even coma.

Cases with a fatal outcome have been reported, mainly in cases of association with other psychotropic substances.

Sulpiride is partially eliminated by haemodialysis.

There is no specific antidote to sulpiride.

Symptomatic treatment, resuscitation under close respiratory and continuous cardiac monitoring (risk of prolongation of the QT interval and ventricular arrhythmia), which will be continued until the patient recovers.

If severe extrapyramidal syndrome occurs, administer an anticholinergic

Pharmacotherapeutic class: ANTIPSYCHOTIC NEUROLEPTIC BENZAMIDE, ATC code: N05AL01.

Sulpiride interferes with cerebral dopaminergic nerve transmission and, at low doses, exerts an activating action simulating a dopaminomimetic effect. At higher doses, sulpiride also has an antiproductive action.

Absorption

Administered orally, the plasma peak of sulpiride is reached in 3 to 6 hours; it is 0,25 mg/l after administration of one capsule of 50 mg.

The bioavailability of oral forms is 25 to 35 %, with high inter-individual variability.

The kinetics of sulpiride remain linear after administration at doses ranging from 50 to 300 mg.

Distribution

Sulpiride distributes rapidly into tissues: the apparent volume of distribution at equilibrium is 0,94 L/kg.

The degree of protein binding is approximately 40 %.

Sulpiride distributes poorly into breast milk and crosses the placental barrier.

Biotransformation

Sulpiride is poorly metabolised in humans.

Elimination

Excretion of sulpiride is essentially renal, by glomerular filtration. The total clearance is 126 mL/min. The plasma elimination half-life is 7 hours.

3 years

Store at a temperature not exceeding 30 °C.

No special requirements.

List I

Marketing authorisation (AMM)

CIP 3400930328972 (Plq/30).

Price:

2,32 euros (Plq/30).

Social Security reimbursement at 30 % on the basis of the TFR: 2,32 euros (Plq/30). Collective.