Composition:

Each tablet contains 200mg Sulpiride

Each 5ml oral solution contains  200mg Sulpiride

Pharmacodynamics:

Sulpiride is a selective dopamine D2 antagonist with antipsychotic and antidepressant activity.

Sulpiride is a member of the group of substituted benzamides

One of the characteristics of Sulpiride is its bimodal activity, as it has both antidepressant and neuroleptic properties

Pharmacokinetics:

Peak sulpiride serum levels are reached 3 - 6 hours after an oral dose. The plasma half-life in man is approximately 8 hours. Approximately 40% sulpiride is bound to plasma proteins. 95% of the compound is excreted in the urine and faeces as unchanged sulpiride.

Indications:

For 50 mg: Neurotic states with inhibition, Psychosomatic components of organic disease and antipsychotic for the elderly.

For 200, 400 mg: Acute and chronic schizophrenia.

Contraindications:

• Phaeochromocytoma and acute porphyria.
• Hypersensitivity to sulpiride or to any of the excipients.
• Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas and breast cancer.
• Association with levodopa or anti-parkinsonian drugs (including ropinirole)
• severe renal and hepatic impairment and blood disorders.
• Bone marrow suppression.

Warning and precautions:

• 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 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: Sulpiride is not licenced for the treatment of dementia-related behavioural disturbances.
• 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 Dolmatil and preventative measures undertaken.
• 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.
• When neuroleptic treatment is absolutely necessary in a patient with Parkinson's disease, sulpiride can be used, although caution is in order.
• Neuroleptics may lower the epileptogenic threshold. Cases of convulsions, sometimes in patients with no previous history, have been reported with sulpiride. Caution is advised in prescribing it for patients with unstable epilepsy, and patients with a history of epilepsy should be closely monitored during therapy with sulpiride.
• In patients requiring sulpiride who are receiving anti-convulsant therapy, the dose of the anti-convulsant should not be changed.
• 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. As with all drugs for which the kidney is the major elimination pathway, the dose should be reduced and titrated in cases of renal insufficiency.
• Sulpiride induces a prolongation of the QT interval. 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, 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.
• 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.
• Avoid concomitant treatment with other neuroleptics.
• Sulpiride should be used with caution in patients with stroke risk factors.
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
• Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including Sulpiride. Unexplained infections or fever may be evidence of blood dyscrasia and requires immediate haematological investigation.
• 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.

Effects on ability to drive and use machines:

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

Pregnancy and Lactation:

The use of sulpiride is not recommended during pregnancy because of the limited experience.

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. Consequently, newborns should be monitored carefully.

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

Drug interactions:

Associations contraindicated:

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

 Associations not recommended:

• Alcohol enhances the sedative effects of neuroleptics. Consumption of alcoholic beverages and drugs containing alcohol should be avoided.
• Combination with the following medications which could induce torsades de pointes or prolong the QT interval:

• Bradycardia-inducing medications such as beta-blockers, bradycardia-inducing calcium channel blockers such as (diltiazem and verapamil, clonidine); digitalis.
• Medications which induce electrolyte imbalance, in particular those causing hypokalaemia: hypokalaemic diuretics, stimulant laxatives, IV amphotericin B, glucocorticoids, tetracosactides. 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, haloperidol; methadone, imipramine antidepressants; lithium, cisapride, thioridazine, IV erythromycin, halofantrine, pentamidine.

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: lithium increases the risk of extrapyramidal side effects. Discontinuation of both drugs is recommended at first signs of neurotoxicity.

Side effects :

Common: hyperprolactinaemia, insomnia, sedation or drowsiness, extrapyramidal disorder (these symptoms are generally reversible upon administration of antiparkinsonian medication), Parkinsonism, tremor, akathisia, constipation, increased hepatic enzyme, maculo-papular rash,  breast pain, galactorrhoea, weight gain.

Uncommon: leukopenia, hypertonia, dyskinesia, dystonia, orthostatic hypotension, salivary hypersecretion, breast enlargement, amenorrhoea, abnormal orgasm, erectile dysfunction.

Dosage and Administration:

Acute and chronic schizophrenia:

 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 the dose 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 dosage of 400-600 mg twice daily.

Inhibitory behaviour and Psychosomatic Component of Organic Disease: as doctor prescribed.

Antipsychotic for the elderly: started at 100 mg once daily (or 50 mg twice daily) and slowly increased according to response.

Ulcer disease: 50 mg 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.

Children: Clinical experience in children under 14 years of age is insufficient to permit specific recommendations.

Overdose:

The range of single toxic doses is 1 to 16g but no death has occurred even at the 16g dose.

The clinical manifestations of poisoning vary depending upon the size of the dose taken. After single doses of 1 to 3g restlessness and clouding of consciousness have been reported and (rarely) extrapyramidal symptoms. Doses of 3 to 7g may produce a degree of agitation, confusion and extrapyramidal symptoms more than 7g can cause, in addition, coma and low blood pressure.  Comas which have occurred after large doses have lasted up to four days.

Sulpiride is partly removed by haemodialysis. Treatment is only symptomatic. Emetic drugs are unlikely to be effective in Sulpiride overdosage.