SULPIREN Tablet Ref.[28259] Active ingredients: Sulpiride

Warnings

Increased motor agitation has been reported at high dosage in a small number of patients: in aggressive, agitated or excited phases of the disease process, low doses of sulpiride may aggravate symptoms. Care should be exercised where hypomania is present.

Extrapyramidal reactions, principally akathisia and tremor have been reported in a small number of cases.

As with other neuroleptics, neuroleptic malignant syndrome, a potentially fatal complication, which is characterised by hyperthermia, muscle rigidity and autonomic dysfunction may occur. In case of hyperthermia of undiagnosed origin, sulpiride should be discontinued.

Sulpiride induces slight EEG modifications. Neuroleptics may lower the epileptogenic threshold and some cases of convulsions have been reported with sulpiride (see section 4.8). Therefore patients with a history of epilepsy should be closely monitored during sulpiride therapy.

In elderly patients, as with other neuroleptics, sulpiride should be used with particular caution (see section 4.2).

In children, efficacy and safety of sulpiride have not been thoroughly investigated. Therefore, caution should be exercised when prescribing to children (see section 4.2).In patients with aggressive behaviour or agitation with impulsiveness, sulpiride could be given with a sedative.

When neuroleptic treatment is absolutely necessary in a patient with Parkinson’s disease, sulpiride can be used, although caution is in order.

In patients requiring Sulpiren who are receiving anti-convulsant therapy, the dose of the anti-convulsant should not be changed. Cases of convulsions, sometimes in patients with no previous history, have been reported.

As with all drugs for which the kidney is the major elimination pathway, the dose should be reduced and titrated in small steps in cases of renal insufficiency.
Initiation of treatment in schizophrenia should only be undertaken by a specialist under whose regular supervision the patients should remain.

Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including sulpiride. Unexplained sore throat, lymphadenopathy, infections or fever may be evidence of blood dyscrasia (see section 4.8) and requires immediate haematological investigation.

Sulpiride has an anticholinergic effect and, therefore, should be used with caution in patients with a history of glaucoma, ileus, congenital digestive stenosis, urine retention or hyperplasia of the prostate.

Sulpiride should be used with caution in hypertensive patients, especially in the elderly population, due to the risk of hypertensive crisis. Patients should be adequately monitored.

Prolongation of the QT interval

Sulpiride may induce a prolongation of the QT interval (see section 4.8). This effect is known to potentiate the risk of serious ventricular arrhythmias such as torsade de pointes.

Before any administration, and if possible according to the patient’s clinical status, it is recommended to monitor factors which could favour the occurrence of this rhythm disorder, such as for example:

• Bradycardia less than 55 bpm
• Electrolyte imbalance in particular hypokalaemia
• Congenital prolongation of the QT interval
• On-going treatment with a medication likely to produce pronounced bradycardia (< 55 bpm),
• hypokalaemia,
• decreased intracardiac conduction,
• or prolongation of the QTc interval (see section 4.5)

Sulpiride should be prescribed with caution in patients presenting with these factors and patients with cardiovascular disorders which may predispose to prolongation of the QT interval.

Stroke

In randomised clinical trials versus placebo performed in a population of elderly patients with dementia and treated with certain atypical antipsychotic drugs, a 3-fold increase of the risk of cerebrovascular events has been observed. The mechanism of such risk increase is not known. An increase in the risk with other antipsychotic drugs, or other population of patients cannot be excluded. Sulpiride should be used with caution in patients with stroke risk factors.

Increased Mortality in Elderly people with Dementia

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Data from two large observational studies showed that elderly patients with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

Although the causes of death in clinical trials with atypical antipsychotics were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Sulpiride is not licensed for the treatment of dementia-related behavioural disturbances.

Venous thromboembolism

Cases of venous thromboembolism (VTE), sometimes fatal have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Sulpiren and preventive measures undertaken.

As hyperglycaemia has been reported in patients treated with atypical antipsychotic agents, patients with an established diagnosis of diabetes mellitus or with risk factors for diabetes who are started on sulpiride should get appropriate glycaemic monitoring.

Avoid concomitant prescription of other antipsychotics.

Sulpiren contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Associations contraindicated

Levodopa antiparkinsonian drugs (including ropinirole): reciprocal antagonism of effects between levopoda or antiparkinsonian drugs (including ropinirole) and neuroleptics.

Associations not recommended

Alcohol: alcohol enhances the sedative effects of neuroleptics.

Avoid the consumption of alcoholic beverages and drugs containing alcohol.

Combination with the following medications which could induce torsades de pointes or prolong the QT interval (see section 4.4):

• Bradycardia-inducing medications such as beta-blockers, bradycardia-inducing calcium channel blockers such as diltiazem and verapamil, clonidine, guanfacine; digitalis.
• Medications which induce electrolyte imbalance, in particular those causing hypokalaemia: (such as hypokalaemic diuretics, stimulant laxatives, IV amphotericin B, glucocorticoids, tetracosactides. Hypokalaemia should be corrected.

Electrolyte imbalance should be corrected

• Class Ia antiarrhythmic agents such as quinidine, disopyramide.
• Class III antiarrhythmic agents such as amiodarone, sotalol.
• Other medications such as pimozide, sultopride, haloperidol; imipramine antidepressants; lithium, bepridil, cisapride, thioridazine, methadone IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin.

Associations to be taken into account

Antihypertensive agents: antihypertensive effect and possibility of enhanced postural hypotension (additive effect).

CNS depressants including narcotics, analgesics, sedative H1 antihistamines, barbiturates, benzodiazepines and other anxiolytics, clonidine and derivatives.

Antacids or sucralfate: The absorption of sulpiride is decreased after co-administration. Therefore, sulpiride should be administered two hours before these drugs.

Lithium increases the risk of extrapyramidal adverse reactions. Discontinuation of both drugs is recommended at first signs of neurotoxicity.

Sulpiride may modify response to metoclopramide therapy.

Pregnancy

A decrease in fertility linked to the pharmacological effects of the drug (prolactin mediated effect) was observed in treated animals. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embyonal/fetal development and/or postnatal development. In humans, very limited clinical data on exposed pregnancies are available. In most cases of foetal or neonatal disorders reported in the context of sulpiride use during pregnancy, alternative explanations can be suggested and seem more likely. Therefore the use of sulpiride is not recommended during pregnancy because of the limited experience. If sulpiride is used during pregnancy, appropriate monitoring of the neonate should be considered in view of sulpiride safety profile.

Neonates exposed to antipsychotics (including Sulpiren) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery (see section 4.8). There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Breast-feeding

Sulpiride has been found in the breast milk in treated women. Therefore breast-feeding is not recommended during treatment.

Even used as recommended, sulpiride may cause sedation so that the ability to drive vehicles or operate machinery can be impaired. (see section 4.8).

According to MedDRA frequency convention, the side effects can be: very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and not known (cannot be estimated from the available data).

Blood and lymphatic system disorders (see section 4.4)

Uncommon: leukopenia

Not known: neutropenia, agranulocytosis

Immune system disorders

Not known: anaphylactic reactions: urticaria, dyspnea, hypotension, and anaphylactic shock

Endocrine disorders

Common: hyperprolactinaemia

Psychiatric disorders

Common: insomnia

Not known: confusion

Nervous system disorders

Common: sedation or drowsiness, extrapyramidal disorder, Parkinsonism, Tremor, Akathisia

Uncommon: hypertonia, dyskinesia, dystonia

Rare: oculogyric crisis

Not known: malignant neuroleptic syndrome, hypokinesia, tardive dyskinesia (have been reported, as with all neuroleptics, after a neuroleptic administration of more than 3 months. Antiparkinsonian medication is ineffective or may induce aggravation of the symptoms), convulsion

Cardiac disorders

Rare: ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia

Not known: electrocardiogram QT prolonged, cardiac arrest, torsade de pointes, sudden death (see section 4.4)

Vascular disorders

Uncommon: orthostatic hypotension

Not known: venous embolism, pulmonary embolism, deep vein thrombosis (see section 4.4)

Gastrointestinal disorders

Uncommon: salivary hypersecretion

Hepatobiliary disorders

Common: hepatic enzyme increased

Skin and subcutaneous tissue disorders

Common: maculo-papular rash

Musculoskeletal and connective tissue disorders

Not known: torticollis, trismus

Pregnancy, puerperium and perinatal conditions

Not known: extrapyramidal symptoms, drug withdrawal syndrome neonatal (see section 4.6)

Reproductive system and breast disorders

Common: breast pain, galactorrhoea

Uncommon: breast enlargement, amenorrhoea, orgasm abnormal, erectile dysfunction

Not known: gynaecomastia

General disorders and administration site conditions

Common: weight gain

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

Not applicable.