Mechanism of effect
In contrast to most other neuroleptics which block both dopamine D1 and D2 receptors, Sulpiride is more selective and acts primarily as a dopamine D2 antagonist. Sulpiride appears to lack effects on norepinephrine, acetylcholine, serotonin, histamine, or gamma-aminobutyric acid (GABA) receptors.
Pharmacodynamic
Sulpiride is a substituted benzamide derivative and a selective dopamine D2 antagonist with antipsychotic and antidepressant activity.
Pharmacokinetics
Absorption
Sulpiride is absorbed slowly from the gastrointestinal tract. Its oral bioavailability is only 25 to 35% with marked interindividual differences.
Volume of distributionNot AvailableProtein bindingNot AvailableMetabolismNot AvailableRoute of eliminationNot AvailableHalf-life
6 to 8 hours
ClearanceNot Available
Drug indications
The treatment of acute and chronic schizophrenia.
Dosage
Adults
A starting dose of 400mg to 800mg daily, given as one or two tablets twice daily (morning and early evening) is recommended.
Predominantly positive symptoms (formal thought disorder, hallucinations, delusions, incongruity of affect) respond to higher doses, and a starting dose of at least 400mg twice daily is recommended, increasing if necessary up to a suggested maximum of 1200mg twice daily. Increasing the dose beyond this level has not been shown to produce further improvement.
Predominantly negative symptoms (flattening of affect, poverty of speech, anergia, apathy, as well as depression) respond to doses below 800mg daily; therefore, a starting dose of 400mg twice daily is recommended. Reducing this dose towards 200mg twice daily will normally increase the alerting effect of sulpiride.
Patients with mixed positive and negative symptoms, with neither predominating, will normally respond to a dose of 400mg-600mg twice daily.
Elderly
The same dose ranges are applicable in the elderly, but the dose should be reduced if there is evidence of renal impairment.
Paediatric population
Clinical experience in children under 14 years of age is insufficient to permit specific recommendations.
Method of administration
For oral use.
Drug contraindications
Phaeochromocytoma and acute porphyria.
Hypersensitivity to sulpiride
Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas and breast cancer
Association with levodopa or antiparkinsonian drugs (including ropinirole)
Side effects
The following frequency rating is used, when applicable:
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); not known (cannot be estimated from the available data).
Blood and lymphatic system disorders :
Uncommon: Leukopenia.
Not known: Neutropenia, agranulocytosis
Immune system disorders:
Not known: Anaphylactic reactions including urticaria, dyspnoea, hypotension and anaphylactic shock.
Endocrine disorders:
Common: Hyperprolactinaemia
Psychiatric disorders:
Common: Insomnia.
Not known: Confusion
Nervous system disorders:
Common: Sedation or drowsiness, extrapyramidal disorder (these symptoms are generally reversible upon administration of antiparkinsonian medication), Parkinsonism, tremor, akathisia.
Uncommon: Hypertonia, dyskinesia, and dystonia.
Rare: Oculogyric crisis.
Not known: Neuroleptic malignant syndrome, hypokinesia, tardive dyskinesia (have been reported, as with all neuroleptics, after a neuroleptic administration of more than three months. Antiparkinsonian medication is ineffective or may induce aggravation of the symptoms), convulsion.
Metabolism and nutrition disorders:
Not known: hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Cardiac disorders:
Rare: Ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia.
Not known: electrocardiogram QT prolonged, cardiac arrest, torsade de pointes, sudden death .
Vascular disorders:
Uncommon: Orthostatic hypotension.
Not known: Venous embolism, pulmonary embolism, deep vein thrombosis
Respiratory, thoracic and mediastinal disorders:
Not known: pneumonia aspiration (mainly in association with other CNS depressants).
Gastrointestinal disorders:
Common: constipation
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
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.
Alerts
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 mania or hypomania is present.
Extrapyramidal reactions, principally akathisia have been reported in a small number of cases. If warranted, reduction in dosage or anti-parkinsonian medication may be necessary.
As with other neuroleptics, neuroleptic malignant syndrome, a potentially fatal complication, which is characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated CPK levels, has been reported. In such an event, or in the event of hyperthermia of undiagnosed origin, all antipsychotic drugs, including sulpiride, should be discontinued.
Elderly patients are more susceptible to postural hypotension, sedation and extrapyramidal effects.
In patients with aggressive behaviour or agitation with impulsiveness, sulpiride could be given with a sedative.
Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia have been described after abrupt cessation of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) have been reported. Therefore, gradual withdrawal is advisable.
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 licenced for the treatment of dementia-related behavioural disturbances.
Venous thromboembolism:
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.
Breast cancer:
Sulpiride may increase prolactin levels. Therefore, caution should be exercised and patients with a history or a family history of breast cancer should be closely monitored during sulpiride therapy.
Points of recommendation
Try to give medicines at about the same times each day, to help you remember.
If you are not sure a medicine is working, contact your doctor but continue to give the medicine as usual in the meantime. Do not give extra doses, as you may do harm.
Only give this medicine to your child. Never give it to anyone else, even if their condition appears to be the same, as this could do harm.
Make sure that you always have enough medicine. Order a new prescription at least 2 weeks before you will run out.
Make sure that the medicine you have at home has not reached the ‘best before’ or ‘use by’ date on the packaging. Give old medicines to your pharmacist to dispose of.
Pregnancy level
There are only very limited data available from the use of sulpiride in pregnant women. The safety of sulpiride during human pregnancy has not been established.
Sulpiride crosses the placenta. Studies in animals are insufficient with respect to reproductive toxicity (see section 5.3).
The use of sulpiride is not recommended during pregnancy and in women of child bearing potential not using effective contraception, unless the benefits justify the potential risks.
Neonates exposed to antipsychotics (including Sulpiride 200mg Film-Coated Tablets) 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.
Breast feeding warning
Sulpiride is excreted into breastmilk in rather large amounts, far above the accepted value of 10% of the maternal weight-adjusted dosage in some cases, but blood concentrations in breastfed infants have not been evaluated. There is insufficient information on the effects of sulpiride in newborns/ infants.
A decision must be made whether to discontinue breast-feeding or to abstain from sulpiride therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Drug forms
Dolmatil®, Sulpor®
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