Special warnings and precautions for use
As with other neuroleptics, Neuroleptic Malignant Syndrome, characterized 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 and intermittent treatment should be considered (see Section 4.2).
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.
Acute withdrawal symptoms including nausea, vomiting and insomnia have very rarely been described after abrupt cessation of high doses of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisa, dystonia and dyskinesia) has been reported. Therefore, gradual withdrawal is advisable.
Prolongation of the QT interval
Amisulpride induces a dose-dependent prolongation of the QT interval. This effect, known to potentiate the risk of serious ventricular arrhythmias such as torsades de pointes is enhanced by the pre-existence of bradycardia, hypokalaemia, congenital or acquired long QT interval. Caution should be exercised when amisulpride is prescribed in patients with known cardiovascular disease or family history of QT prolongation.
Hypokalaemia should be corrected.
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:
- bradycardia less than 55 bpm,
- 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
Caution should be exercised when amisulpride is prescribed in patients with known cardiovascular disease or family history of QT prolongation.
Concomitant antipsychotics should be avoided.
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:
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death in clinical trials with atypical antipsychotics were varied, most of the deaths appeared to be either cardiovascular (e.g. hearth failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Amisulpride is not licensed 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 Amisulpride and preventive measures undertaken
Amisulpride 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 Amisulpride therapy.
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including Amisulpride. Unexplained infections or fever may be evidence of blood dyscrasia (see section 4.8), and requires immediate haematological investigation.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.