Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
As with other neuroleptics, Neuroleptic Malignant Syndrome (NMS) may occur. This condition is characterized by high fever, muscle rigidity, autonomic dysfunction, clouding of consciousness, rhabdomyolysis and elevated CPK values, and it is potentially fatal.
If a patient develops signs and symptoms indicative for NMS or presents with unexplained hyperthermia, particularly at high daily doses, all antipsychotic agents including Pride must be discontinued. Rhabdomyolysis has also been observed in patients without Neuroleptic Malignant Syndrome.
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.

Pride is eliminated by the renal route. In cases of renal insufficiency, the dose should be decreased or intermittent treatment could be considered (see section 4.2).

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

In elderly patients, Pride, like other neuroleptics, should be used with particular caution because of a possible risk of hypotension or sedation.
Reduction in dosage may also be required because of renal insufficiency.

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

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. Pride should be used with caution in patients with stroke risk factors.

Withdrawal symptoms including nausea, vomiting and insomnia have been described after abrupt cessation of high therapeutic doses of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported with amisulpride. Therefore, gradual withdrawal of amisulpride is advisable.
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.

Elderly patients 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 – 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. heart 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.

Pride is not licensed for the treatment of dementia-related behavioral 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 Pride and preventive measures undertaken.

Breast cancer
Pride causes an 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 Pride therapy. Pride is contraindicated in patients with breast cancer (see sections 4.3 and 4.8).


Benign pituitary tumor
Amisulpride may increase prolactin levels. Cases of benign pituitary tumors such as prolactinoma have been observed during amisulpride therapy (see section 4.8). In case of very high levels of prolactin or clinical signs of pituitary tumor (such as visual field defect and headache), pituitary imaging should be performed. If the diagnosis of pituitary tumor is confirmed, the treatment with amisulpride must be stopped (see section 4.3).
Severe liver toxicity has been reported with amisulpride use. Patients should be instructed to report immediately signs such as asthenia, anorexia, nausea, vomiting, abdominal pain or icterus to a physician. Investigations including clinical examination and biological assessment of liver function should be undertaken immediately (see section 4.8).

Excipients
Lactose
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicine.

Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

Effects on Driving

4.7   Effects on ability to drive and use machines
Even used as recommended, Pride may cause somnolence and blurred vision so that the ability to drive vehicles or operate machinery can be impaired (see Section 4.8 Undesirable effects).