Amisulpride

Co-administration of amisulpride with medicines that increase the risk of ventricular tachycardia like “torsades de pointes”, is not recommended.

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

Amisulpride may enhance the central effects of alcohol.

Caution is advised when prescribing amisulpride with CNS depressants including narcotics, anaesthetics, analgesics, sedative H₁ antihistamines, barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives, antihypertensive drugs and other hypotensive medications.

Co-administration of amisulpride with bradycardia-inducing drugs, such as β-blockers, bradycardia-like calcium channel blockers, such as diltiazem and verapamil, clonidine, guanapine, digitalis derivatives, is not recommended.

Co-administration of amisulpride and clozapine may lead to an increase in plasma levels of amisulpride.

There are only limited data available from the use of amisulpride in pregnant women. The safety of amisulpride during human pregnancy has not been established.

Amisulpride crosses the placenta.

Studies in animals have shown reproductive toxicity.

The use of amisulpride is not recommended during pregnancy and in women of childbearing potential not using effective contraception, unless the benefits justify the potential risks.

Neonates exposed to antipsychotics (including amisulpride) 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.

Amisulpride is excreted into breastmilk in rather large amounts 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 amisulpride in newborns/infants. A decision must be made whether to discontinue breast-feeding or to abstain from amisulpride therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

A decrease in fertility linked to the pharmacological effects of the drug (prolactin-mediated effect) was observed in treated animals.

Even used as recommended, amisulpride may cause somnolence and blurred vision so that the ability to drive vehicles or operate machinery can be impaired.

Adverse effects have been ranked under headings of frequency using the following convention: very common (≥1/10); common (≥1/100; <1/10); uncommon (≥1/1,000; <1/100); rare (≥1/10,000; <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Uncommon: leukopenia, neutropenia

Rare: agranulocytosis

Immune system disorders

Uncommon: allergic reaction

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.

Rare: benign pituitary tumour such as prolactinoma

Metabolism and nutrition disorders

Uncommon: hyperglycaemia, hypertriglyceridemia and hypercholesterolaemia

Rare: hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Psychiatric disorders

Common: insomnia, anxiety, agitation, orgasmic dysfunction

Uncommon: confusion

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

Uncommon: seizures, 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.

Rare: neuroleptic Malignant Syndrome, which is a potentially fatal complication

Not known: restless legs syndrome

Eye disorders

Common: blurred vision

Cardiac disorders

Uncommon: bradycardia

Rare: QT interval prolongation, ventricular arrhythmias such as torsade de pointes, ventricular tachycardia, ventricular fibrillation, cardiac arrest, sudden death

Vascular disorders

Common: hypotension

Uncommon: increase in blood pressure

Rare: venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis

Respiratory, thoracic and mediastinal disorders

Uncommon: nasal congestion, pneumonia aspiration (mainly in association with other antipsychotics and CNS depressants)

Gastrointestinal disorders

Common: constipation, nausea, vomiting, dry mouth

Hepatobiliary disorders

Uncommon: hepatocellular injury

Skin and subcutaneous tissue disorders

Rare: angioedema, urticaria

Not known: photosensitivity reaction

Musculoskeletal and connective tissue disorders

Uncommon: osteopenia, osteoporosis

Renal and urinary disorders

Uncommon: urinary retention

Pregnancy, puerperium and perinatal conditions

Not known: drug withdrawal syndrome neonatal

Investigations

Common: weight gain

Uncommon: elevations of hepatic enzymes, mainly transaminases