AMISULPRIDE

What it is

Amisulpride is available as tablets containing 50 mg, 100 mg, 200 mg or 400 mg of amisulpride as the active ingredient. Amisulpride tablets are intended for oral administration.

Approved indications

— 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.

Dosing overview

Dosing varies according to symptom profile. For acute psychotic episodes, oral doses between 400 mg/d and 800 mg/d are recommended, with daily dose increasing to up to 1200 mg/d in individual cases. Doses above 800 mg/d have not been shown to be superior to lower doses and may increase the incidence of adverse events. Amisulpride should be administered twice daily for doses above 400 mg. For patients characterised by predominant negative symptoms, oral doses between 50 mg/d and 300 mg/d are recommended. Maintenance treatment should be established individually with the minimally effective dose. In renal insufficiency, the dose should be reduced to half in patients with creatinine clearance between 30–60 mL/min and to a third in patients with creatinine clearance between 10–30 mL/min.

Key safety warnings

Neuroleptic malignant syndrome is a potentially fatal syndrome that has been reported in association with antipsychotic medicines, including amisulpride. It is characterised by hyperthermia, muscle rigidity, rhabdomyolysis, autonomic instability, and elevated CPK. In the event of any symptoms which could suggest neuroleptic malignant syndrome, all antipsychotic medicines including amisulpride should be discontinued. Amisulpride produces a dose-dependent prolongation of the QT interval, which is known to potentiate the risk of serious ventricular arrhythmias such as torsades de pointes. Before administration, factors which could favour the onset of this rhythm disorder should be monitored, including bradycardia less than 55 bpm, electrolyte imbalance (particularly hypokalaemia), congenital prolongation of the QT interval, and concurrent treatment with medications likely to produce pronounced bradycardia, hypokalaemia, or QT prolongation. Amisulpride can lower the seizure threshold and patients with a history of seizures should be closely monitored during amisulpride therapy. Leucopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including amisulpride. Unexplained infections or fever may be evidence of blood dyscrasia and requires immediate haematological investigation. Amisulpride causes an increase in plasma prolactin levels which is reversible after discontinuation of the medicine. This may result in galactorrhoea, amenorrhoea, gynacomastia, breast pain, orgasmic dysfunction and impotence.

Contraindications

Amisulpride is contraindicated in patients with hypersensitivity to the active ingredient or to other ingredients of the product, concomitant prolactin-dependent tumours such as pituitary gland prolactinomas and breast cancer, phaeochromocytoma, children up to puberty, and lactation. It is also contraindicated in combination with medications which could induce torsades de pointes, including Class Ia antiarrhythmic agents such as quinidine and disopyramide, Class III antiarrhythmic agents such as amiodarone and sotalol, and other medications such as bepridil, cisapride, sultopride, thioridazine, methadone, intravenous erythromycin, intravenous vincamine, halofantrine, pentamidine, and sparfloxacin. Amisulpride is also contraindicated in combination with levodopa due to reciprocal antagonism between levodopa and neuroleptics.

PBS listing

Amisulpride tablets are listed on the PBS at strengths of 100 mg, 200 mg and 400 mg with streamlined restriction. The ex-manufacturer prices are A$4.75 for 100 mg tablets, A$20.48 for 200 mg tablets, and A$37.14 for 400 mg tablets.

Regulatory history

Amisulpride was first listed on the ARTG on 29 January 2016, with seven registered variants comprising 50 mg, 100 mg, 200 mg and 400 mg tablets.