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Amisulpride

Drug Approvals

(British Approved Name, rINN)

International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish): Amisulprid; Amisulprid; Amisulprida; Amisulpridas; Amisulpridi; Amisulpridum; Amiszulprid; DAN-216

C17H27N3O4S = 369.5

CAS 71675-85-9

ATC N05AL05

Pharmacopoeias. In Europe.

European Pharmacopoeia, 6th ed. (Amisulpride). A white or almost white crystalline powder. Practically insoluble in water sparingly soluble in dehydrated alcohol freely soluble in dichloromethane.

Amisulpride

Adverse Effects, Treatment, and Precautions

Although amisulpride may share some of the adverse effects seen with the classical antipsychotics (see Chlorpromazine), the incidence and severity of such effects may vary. Insomnia, anxiety, and agitation are common adverse effects with amisulpride. Other less common effects include drowsiness and gastrointestinal disorders such as constipation, nausea, vomiting, and dry mouth. Allergic reactions, abnormal liver function tests, and seizures have been reported rarely. Hyperprolactinaemia, which may result in galactorrhoea, amenorrhoea, impaired fertility, gynaecomastia, breast pain, and sexual dysfunction, has occurred with amisulpride use. Weight gain has also been noted. Dose-related extrapyramidal dysfunction may occur, but symptoms such as acute dystonia, parkinsonism, and akathisia are generally mild at licensed doses. Tardive dyskinesia has been reported after long-term use and there have been rare cases of neuroleptic malignant syndrome. Hypotension and bradycardia have been reported occasionally QT prolongation, in rare cases leading to torsade de pointes, has also been noted. The risk of QT prolongation is increased by pre-existing conditions such as bradycardia, hypokalaemia, and congenital or acquired QT prolongation patients should be reviewed for these conditions before starting amisulpride treatment. Certain medications may also increase the risk (see Interactions, below). Amisulpride should not be given to patients with phaeo-chromocytoma or prolactin-dependent tumours. It should be used with caution in patients with severe renal impairment, or a history of epilepsy or Parkinson’s disease. The risk of hypotension and sedation is increased in elderly patients.

Amisulpride may affect the performance of skilled tasks including driving.

Withdrawal symptoms have occurred rarely when amisulpride has been stopped abruptly a gradual dose reduction may be appropriate when stopping amisulpride.

Dementia. The FDA has issued advice against the use of atypical antipsychotics in the treatment of behavioural problems in elderly patients with dementia after analysis of placebo-controlled studies showed an increased risk of mortality with certain drugs of this class. See under Risperidone.

Effects on body-weight. A review has suggested that the risk of weight gain with amisulpride treatment is less than with olanzapine or risperidone, although cases have been reported. The increased risk of weight gain with some atypical antipsychotics is also discussed under Adverse Effects of Clozapine.

Effects on carbohydrate metabolism. The increased risk of glucose intolerance and diabetes mellitus with some atypical antipsychotics, and recommendations on monitoring, are discussed under Adverse Effects of Clozapine.

Effects on lipid metabolism. The increased risk of hyperlip-idaemia with some atypical antipsychotics is discussed under Adverse Effects of Chlorpromazine. See also Effects on Carbohydrate Metabolism under Adverse Effects of Clozapine.

Overdosage. The effects of overdosage of amisulpride in 2 patients have been reported. The first patient had taken about 3 g of amisulpride and an unknown amount of dosulepin and was found to have had a blood-amisulpride concentration of 9.63 micrograms/mL. Generalised convulsions, which resolved spontaneously, were followed by coma, motor restlessness, tachycardia, and slight prolongation of the QT interval. The patient was treated with gastric lavage and had recovered within 48 hours. The second patient, who had been found dead, had a blood-amisulpride concentration of 41.7 micrograms/mL. Severe cardiotoxicity occurred in 4 further cases of amisulpride overdoses of between about 4 and 32 g reported to Australian poisons information centres all 4 had marked QT prolongation, with bundle branch block or torsade de pointes, and one, who was thought to have ingested between 16 and 24 g, died after cardiac arrest.

Pregnancy. For comments on the use of some atypical antipsychotics during pregnancy, see under Precautions of Clozapine.
Amisulpride

Interactions

Amisulpride should not be given with drugs that may induce arrhythmias (including torsade de pointes) such drugs include some antiarrhythmics, cisapride, thioridazine, erythromycin, and halofantrine. The risk of arrhythmias is also increased with drugs that prolong the QT interval, such as pimozide, haloperidol, and tricyclic antidepressants, and with drugs that produce bradycardia or hypokalaemia, including beta blockers, some calcium-channel blockers, clonidine, digoxin, guanfacine, potassium-depleting diuretics, and lithium use of these drugs with amisulpride requires caution.

The central effects of other CNS depressants including alcohol maybe enhanced by amisulpride. Amisulpride may also enhance the effects of antihypertensive drugs. The dopamine-blocking activity of amisulpride may antagonise the actions of dopaminergics such as levo-dopa and they should not be given together.

In 7 patients receiving amisulpride, introduction of lithium resulted in an average increase of 32% of the dose-corrected plasma concentration of amisulpride. An earlier study had noted that plasma concentrations of amisulpride were raised in patients also taking clozapine.

Pharmacokinetics

Amisulpride is absorbed from the gastrointestinal tract but bioavailability is reported to be only about 48%. An initial peak in plasma concentration has been reported to occur 1 hour after oral doses and a second higher peak after 3 to 4 hours. Plasma protein binding is reported to be only about 16%. Metabolism is limited, with most of a dose appearing in the urine as unchanged drug. The terminal elimination half-life is about 12 hours.

Uses and Administration

Amisulpride is a substituted benzamide atypical anti-psychotic. It is reported to have a high affinity for dopamine D2 and D3 receptors. Amisulpride is used mainly in the management of psychoses such as schizophrenia but in some countries it has also been tried in depression.

For acute psychotic episodes in adults and adolescents aged 15 years and over a daily dosage of between 400 and 800 mg may be given orally in 2 divided doses, increased if necessary to 1200 mg daily. For patients with mainly negative symptoms, daily doses between 50 and 300 mg are recommended. Daily doses of up to 300 mg may be given as a single dose. Amisulpride has also been given by intramuscular injection in doses of 400 mg daily.

Administration in renal impairment. For patients with renal impairment, the oral dose of amisulpride should be reduced according to creatinine clearance (CC):

• CC between 30 and 60 mL/minute, half the usual dose

• CC between 10 and 30 mL/minute, one-third the usual dose Similar reductions are also recommended when amisulpride is given intramuscularly.

Schizophrenia. Reviews of amisulpride indicate that it may be more effective than classical antipsychotics against general and negative symptoms of schizophrenia, and has fewer extrapyramidal adverse effects.

Preparations

Proprietary Preparations

 

Argentina: Enorden

Australia: Solian

Austria: Majorem Solian

Belgium: Solian

Brazil: Socian

Chile: Socian

Czech Republic: Deniban Solian

Denmark: Solian

France: Solian

Germany: Amisulid Solian

Greece: Solian

Hong Kong: Solian

Hungary: Amiprid Amitrex

Ireland: Solian

Israel: Solian

Italy: Deniban Solian Sulamid

Mexico: Solian

Norway: Solian

New Zealand: Solian

Philippines: Solian

Poland: Solian

Portugal: Amitrex Socian

Russia: Solian

South Africa: Solian

Singapore Solian

Spain: Amiiandef Solian

Switzerland: Solian

Turkey: Solian

UK: Solian.

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