Sulpiride 400mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Sulpiride 400mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Sulpiride 400mg.
For excipients, see 6.1.
3. PHARMACEUTICAL FORM
Film coated Tablet.
White, oval, film coated tablets marked S400 and breakline on one face and plain on the
reverse.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
The treatment of acute and chronic schizophrenia.
4.2 Posology and method of administration
Adults: The initial dose depends on the nature of the symptoms.
In patients with predominantly negative symptoms the usual starting dose is 400 mg twice daily. This can be reduced to 200mg twice daily as a response occurs, increasing the alerting effect of sulpiride that occurs at lower doses.
In patients with predominantly positive symptoms the usual starting dose is 400mg twice daily increasing if necessary to a suggested maximum of 1200mg twice daily.
In patients with positive and negative symptoms, with neither predominating, a dose of 400mg-600mg twice daily is recommended.
Elderly: Initially one quarter to one half of the adult dose.
Children: Not recommended for children under 14 years of age.
Renal impairment: The dosage should be reduced or the dosage
interval increased.
4.3 Contraindications
• Phaeochromocytoma
• Acute porphyria
• Sensitivity to sulpiride or any of the ingredients of sulpiride tablets.
4.4 Special warnings and precautions for use
Increased motor agitation has been reported at high dosage in a small number of patients given sulpiride. Sulpiride may aggravate symptoms in aggressive, agitated or excited phases of the disease process. Care should be exercised where mania or hypomania is present.
Sulpiride should be given with caution to patients suffering from extrapyramidal disturbances as these may be aggravated by sulpiride.
As with all neuroleptic drugs, the presence of unexplained hyperthermia could indicate the development of neuroleptic malignant syndrome (NMS). In this event treatment with sulpiride and any associated neuroleptic should be discontinued until the origin of the fever has been determined.
Sulpiride should be given with caution to elderly patients and patients with hypertension or renal disease. In the elderly and patients with renal disease the dosage or frequency of administration should be reduced.
Caution is advised when prescribing sulpiride for patients with epilepsy as the condition may be aggravated.
Cases of venous thromboembolism (VTE) 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 Sulpiride and preventive measures undertaken.
Increased Mortality in Elderly people with Dementia
Data from two large observational studies showed that elderly people 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.
Sulpiride is not licensed for the treatment of dementia-related behavioural disturbances.
4.5 Interaction with other medicinal products and other forms of interaction
As with other psychotropic compounds, sulpiride may alter the effect of antihypertensives and increase the effect of CNS depressants including hypnotics, tranquillisers, neuroleptics, analgesics, anaesthetics and alcohol.
Concomitant administration of sucralfate or antacid may reduce the bioavailability of sulpiride.
A reduction in dosage of concomitant anti-parkinsonian medication may be necessary.
4.6 Pregnancy and lactation
Despite the negative results of teratogenicity studies in animals and lack of teratogenic effects observed clinically after long term use in other countries, sulpiride should be avoided during pregnancy particularly during the first trimester, with potential benefits being weighed against possible hazards.
Neonates exposed to antipsychotics (including Sulpiride) 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. There have been reports of agitation, hypertonia,
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.
Sulpiride is excreted into breast milk and its use should be avoided in mothers wishing to breast feed.
4.7 Effects on ability to drive and use machines
Sulpiride is less prone to produce drowsiness than other conventional neuroleptics. Patients receiving high doses of sulpiride should be warned of the hazards of driving or operating machinery until the drug has been shown not to interfere with their physical or mental ability.
4.8 Undesirable effects
Cardiovascular disorders:
- Postural hypotension
- QT interval prolongation and ventricular arrhythmias such as torsade de pointes and ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest, sudden death (see section 4.4).
Endocrine disorders:
-Hyperprolactinaemia
General disorders and administration site conditions:
- As with all neuroleptics, malignant syndrome (see section 4.4) which is a potentially fatal complication
- Weight gain Hepatobiliary disorders:
- Increase in hepatic enzymes Nervous system disorders:
- Sedation or drowsiness. Insomnia has been reported.
- Extrapyramidal symptoms and related disorders:
-parkinsonism and related symptoms: tremor, hypertonia, hypokinesia, hypersalivation
-acute dyskinesia and dystonia (spasm torticollis, oculogyric crisis, trismus) -akathisia
These symptoms are generally reversible upon administration of antiparkinsonian medication.
- Tardive dyskinesia (characterised by rhythmic, involuntary movements primarily of the tongue and/or the face) 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.
- Convulsions have been reported, in particular in patients with epilepsy. (see section 4.4)
Reproductive system and breast disorders:
Disorders related to hyperprolactinaemia:
- Galactorrhoea
- Amenorrhoea
- Gynaecomastia
- Breast enlargement and breast pain
- Orgasmic dysfunction and erectile dysfunction.
Skin and subcutaneous tissue disorders:
- Maculo-papular rash Vascular disorders:
- Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs -Frequency unknown
Pregnancy, puerperium and perinatal conditions:
- Drug withdrawal syndrome neonatal (see section 4.6) - Frequency not known
4.9 Overdose
The range of single toxic doses is 1 to 16g but no deaths have occurred even at a dose of20g.
Symptoms
The clinical manifestations of poisoning vary depending upon the size of the dose taken. After single doses of 1g to 3g restlessness and clouding of consciousness have been reported and (rarely) extrapyramidal symptoms. Doses of 3g to 7g may produce a degree of agitation, confusion and extrapyramidal symptoms; more than 7g can cause, in addition, coma and low blood pressure.
The duration of intoxication is generally short, the symptoms disappearing within a few hours. Comas which have occurred after large doses have lasted up to four days.
There are no specific complications from overdose. In particular no haematological or hepatic toxicity has been reported.
Treatment
Overdose may be treated with alkaline osmotic diuresis and, If necessary, anti-parkinsonian drugs. Emetic drugs are unlikely to be effective. Coma needs appropriate nursing.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Sulpiride is a member of the group of substituted benzamides, which are structurally distinct from the phenothiazines, butyrophenones and thioxanthenes.
Behaviourally and biochemically sulpiride shares with classical neuroleptics a number of properties indicative of cerebral dopamine receptor antagonism. Differences include lack of effect upon noradrenaline or 5HT turnover, negligible anticholinesterase activity, no effect on muscarinic or GABA receptor binding. These findings indicate a major differentiation between sulpiride and classical neuroleptics, which lack such specificity.
One of the characteristics of sulpiride is its bimodal activity, as it has both antidepressant and antipsychotic properties. Schizophrenia characterised by a lack of social contact can benefit strikingly.
Mood elevation is observed after a few days treatment, followed by disappearance of the florid schizophrenic symptoms. The sedative, anti-muscarinic, alpha-blocking and extrapyramidal effects of sulpiride are less pronounced than those characteristically associated with classical neuroleptics of the phenothiazine type.
5.2 Pharmacokinetic properties
The bioavailability of the oral form ranges from 25-40%. Peak sulpiride serum levels are reached 2-6 hours after an oral dose. The plasma half-life in man is 6-8 hours. Sulpiride is less than 40% bound to plasma proteins. Sulpiride crosses the blood-brain barrier. Ninety five percent of the compound is excreted in the urine and faeces as unchanged sulpiride.
5.3 Preclinical safety data
There are no pre-clinical data of any relevance to the prescriber that are additional to those already included in order sections.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate Povidone K30 Microcrystalline cellulose Sodium starch glycollate Magnesium stearate Titanium dioxide, Hydroxypropylmethyl cellulose Polyethylene glycol.
6.2 Incompatibilities
None known
6.3 Shelf life
Three years.
6.4 Special precautions for storage
Do not store above 25 °C
6.5 Nature and contents of container
Blister strip consisting of hard tempered aluminium foil (20 micron) and PVC film (250 micron) containing
10,20,30,40,50,60,70,80,90,100,500,1000,28,56,84,112 tablets.
Polypropylene tablet containers with polyethylene tamper evident lids containing
10, 20, 30,40,50,60,70,80,90,100,500,1000,28,56,84,112 tablets. Polypropylene tablet containers with polyethylene tamper evident lids containing
10, 20, 30,40,50,60,70,80,90,100,500,1000,28,56,84,112 tablets.
6.6 Special precautions for disposal
None.
7. Marketing Authorisation Holder
Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0059
9
10
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
05/02/2009
DATE OF REVISION OF THE TEXT
12/06/2013