| Section 4.1
Deleted: Amisulpride is contraindicated in children under 15 years of age as its safety has not been established
Inserted: The efficacy and safety of amisulpiride from puberty to the age of 18 years have not been established. There are limited data available on the use of amisulpiride in adolescents in schizophrenia. Therefore, the use of amisulpiride from puberty to the age of 18 years is not recommended; in children up to puberty amisulpiride is contraindicated (see section 4.3).
Section 4.3
Children bullet point - 'under 15 years of age' deleted, 'until puberty' added
Deleted: 'women of child bearing potential unless using adequate contraception
Deleted: 'Combination with the following medications which could induce torsades de pointes: • Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide. Combination with levodopa (see Section 4.5 Interactions with other medicinal products and other forms of interaction). • Class III antiarrhythmic agents such as amiodarone, sotalol. • Other medications such as bepridil, cisapride, sultopride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin (see Section 4.5 Interactions with other medicinal products and other forms of interaction. This list is not exhaustive'
Section 4.4
Added: Withdrawal symptoms have been described after abrupt cessation of high therapeutic doses of antipsychotic drugs. The emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported with amisulpride. Therefore, gradual withdrawal of amisulpride is advisable.
Added: 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.
Deleted: Amisulpride induces a dose-dependent prolongation of the QT interval (see Section 4.8 Undesirable effects). This effect is known to potentiate the risk of serious ventricular arrhythmias such as torsades de pointes. Hypokalaemia should be corrected.
Deleted: 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 such as:
• bradycardia less than 55 bpm,
• cardiac disease or family history of sudden death or QT prolongation,
• electrolyte imbalance, in particular hypokalaemia,
• 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 (see Section 4.5 Interaction with other medicinal products and other forms of interaction)
Deleted:Baseline ECG is recommended prior to treatment in all patients especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination.
During therapy, the need for ECG monitoring (e.g. at dose escalation) should be assessed on an individual patient basis.
The dose of amisulpride should be reduced if QT is prolonged and discontinued if QTc is >500ms.
Periodic electrolyte monitoring is recommended particularly if the patient is taking diuretics or during inter-current illness.
Concomitant antipsychotics should be avoided.
Section 4.5
Deleted: Medications which could induce torsades de pointes: • Class Ia antiarrhythmic agents such as quinidine, disopyramide. procainamide. • Class III antiarrhythmic agents such as amiodarone, sotalol. • Other medications such as bepridil, cisapride, sultopride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin. This list is not exhaustive.
Deleted: COMBINATIONS WHICH REQUIRE PRECAUTIONS FOR USE . Medications which enhance the risk of torsades de pointes or could prolong QT interval: • Bradycardia-inducing medications such as beta-blockers, bradycardia-inducing calcium channel blockers such as diltiazem and verapamil, clonidine, guanfacine, digitalis. • Medications which induce hypokalaemia or electrolyte imbalance: hypokalaemic diuretics, stimulant laxatives, IV amphotericin B, glucocorticoids, tetracosactides. Hypokalaemia should be corrected. • Neuroleptics such as pimozide, haloperidol, imipramine antidepressants, lithium.
Deleted: • Dopamine agonists (eg: levodopa) since it may attenuate their action.
Added: • Caution is advised when prescribing amisulpride with medicines known to prolong the QT interval, e.g., class IA antiarrhythmics (e.g., quinidine, disopyramide) and class III antiarrhythmics (e.g., amiodarone, sotalol), some antihistaminics, some other antipsychotics and some antimalarials (e.g., mefloquine (see section 4.4). • Drugs causing electrolyte imbalance
Section 4.8
Added: Skin and subcutaneous tissue disorders: Frequency not known: Angioedema, urticaria
Section 4.9
Added: Fatal outcomes have been reported mainly in combination with other psychotropic agents.
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