Atypical antipsychotic

Amisulpride

Each tablet contains 50mg Amisulpride

Tablet. White to off-white, round, flat-faced tablet, engraved AMI 50 on one side

Amisulpride 50mg Tablets are indicated for the treatment of acute and chronic schizophrenic disorders, in which positive symptoms (such as delusions, hallucinations, thought disorders) and/or negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent, including patients characterised by predominant negative symptoms.

For acute psychotic episodes, oral doses between 400 mg/d and 800 mg/d are recommended. In individual cases, the daily dose may be increased up to 1200 mg/d. Doses above 1200 mg/d have not been extensively evaluated for safety and therefore should not be used. No specific titration is required when initiating the treatment with amisulpride. Doses should be adjusted according to individual response.

For patients with mixed positive and negative symptoms, doses should be adjusted to obtain optimal control of positive symptoms.

Maintenance treatment should be established individually with the minimally effective dose.

For patients characterised by predominant negative symptoms, oral doses between 50 mg/d and 300 mg/d are recommended. Doses should be adjusted individually.

Amisulpride can be administered once daily at oral doses up to 300 mg, higher doses should be administered bid.

The minimum effective dose should be used.

Renal insufficiency: Amisulpride is eliminated by the renal route. In renal insufficiency, the dose should be reduced to half in patients with creatinine clearance (CR_CL) between 30-60 ml/min and to a third in patients with CR_CL between 10-30 ml/min.

As there is no experience in patients with severe renal impairment (CR_CL < 10 ml/min) particular care is recommended in these patients.

Hepatic insufficiency: since the drug is weakly metabolised a dosage reduction should not be necessary.

The efficacy and safety of amisulpiride from puberty to the age of 18 years have not been established. There are limited data available on the use of amisulpiride in adolescents in schizophrenia. Therefore, the use of amisulpiride from puberty to the age of 18 years is not recommended; in children up to puberty amisulpiride is contraindicated

Amisulpride should be used with particular caution because of a possible risk of hypotension or sedation.

• Hypersensitivity to the active ingredient or to other ingredients of the medicinal product

• Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas and breast cancer

• Phaeochromocytoma

• Children till puberty

• Lactation

• Combination with levodopa

As with other neuroleptics, Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated CPK, may occur. In the event of hyperthermia, particularly with high daily doses, all antipsychotic drugs including amisulpride should be discontinued.

Hyperglycaemia has been reported in patients treated with some atypical antipsychotic agents, including amisulpride, therefore patients with an established diagnosis of diabetes mellitus or with risk factors for diabetes who are started on amisulpride, should get appropriate glycaemic monitoring.

Amisulpride is eliminated by the renal route. In cases of severe renal insufficiency, the dose should be decreased orintermittent treatment could be considered.

Amisulpride may lower the seizure threshold. Therefore patients with a history of epilepsy should be closely monitored during amisulpride therapy.

In elderly patients, amisulpride, like other neuroleptics, should be used with particular caution because of a possible risk of hypotension or sedation.

As with other antidopaminergic agents, caution should be also exercised when prescribing amisulpride to patients with Parkinson's disease since it may cause worsening of the disease. Amisulpride should be used only if neuroleptic treatment cannot be avoided.

Withdrawal symptoms have been described after abrupt cessation of high therapeutic doses of antipsychotic drugs. The emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported with amisulpride. Therefore, gradual withdrawal of amisulpride is advisable.

Prolongation of the QT interval

Caution should be exercised when amisulpride is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and concomitant use with neuroleptics should be avoided.

Stroke

In randomized 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 populations of patients cannot be excluded. Amisulpride should be used with caution in patients with stroke risk factors.

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.

Amisulpride is not licensed 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 Solian and preventive measures undertaken.

COMBINATIONS WHICH ARE CONTRAINDICATED

• Levodopa: reciprocal antagonism of effects between levodopa and neuroleptics.

COMBINATIONS WHICH ARE NOT RECOMMENDED

Amisulpride may enhance the central effects of alcohol.

COMBINATIONS TO BE TAKEN INTO ACCOUNT

• CNS depressants including narcotics, anaesthetics, analgesics, sedative H1 antihistamines, barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives

• Antihypertensive drugs and other hypotensive medications

• Caution is advised when prescribing amisulpride with medicines known to prolong the QT interval, e.g., class IA antiarrhythmics (e.g., quinidine, disopyramide) and class III antiarrhythmics (e.g., amiodarone, sotalol), some antihistaminics, some other antipsychotics and some antimalarials (e.g., mefloquine.

• Drugs causing electrolyte imbalance

Clinical trials data

The following adverse effects have been observed in controlled clinical trials. It should be noted that in some instances it can be difficult to differentiate adverse events from symptoms of the underlying disease.

• Nervous system disorders:

Very common: Extrapyramidal symptoms may occur: tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia. These symptoms are generally mild at optimal dosages and partially reversible without discontinuation of amisulpride upon administration of antiparkinsonian medication. The incidence of extrapyramidal symptoms which is dose related, remains very low in the treatment of patients with predominantly negative symptoms with doses of 50-300 mg/day.

Common: Acute dystonia (spasm torticollis, oculogyric crisis, trismus) may appear. This is reversible without discontinuation of amisulpride upon treatment with an antiparkinsonian agent. Somnolence.

Uncommon: Tardive dyskinesia characterized by rhythmic, involuntary movements primarily of the tongue and/or face have been reported, usually after long term administration. Antiparkinsonian medication is ineffective or may induce aggravation of the symptoms. Seizures.

• Psychiatric disorders:

Common: Insomnia, anxiety, agitation, orgasmic dysfunction

• Gastrointestinal disorders

Common: Constipation, nausea, vomiting, dry mouth

• Endocrine disorders:

Common: Amisulpride causes an increase in plasma prolactin levels which is reversible after drug discontinuation. This may result in galactorrhoea, amenorrhoea, gynaecomastia, breast pain, and erectile dysfunction.

• Metabolism and nutrition disorders

Uncommon: Hyperglycemia.

• Cardiovascular disorders

Common: Hypotension

Uncommon: Bradycardia

• Investigations:

Common: Weight gain

Uncommon: Elevations of hepatic enzymes, mainly transaminases

• Immune system disorders

Uncommon: Allergic reaction

Post Marketing data

In addition, cases of the following adverse reactions have been reported through spontaneous reporting only:

• Nervous system disorders:

Frequency not known: Neuroleptic Malignant Syndrome.

• Cardiac disorders:

Frequency not known: QT interval prolongation and ventricular arrhythmias such as torsade de pointes, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest, sudden death.

• Vascular disorders:

Frequency not known: Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs.

•  Skin and subcutaneous tissue disorders:

Frequency not known: Angioedema, urticaria

Aurobindo Pharma Ltd

POM- Prescription

24 January 2012