Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Aventis Pharma Limited, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK Trading as: Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK
As with other neuroleptics, Neuroleptic Malignant Syndrome, a potentially fatal complication, 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 Solian 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.
Solian 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).
Solian may lower the seizure threshold. Therefore patients with a history of epilepsy should be closely monitored during Solian therapy.
In elderly patients, Solian, 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 Solian to patients with Parkinson’s disease since it may cause worsening of the disease. Solian 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 akathisia, dystonia and dyskinesia) has been reported. Therefore, gradual withdrawal of amisulpride is advisable.
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.
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. Solian should be used with caution in patients with stroke risk factors.
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. 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.
Solian 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 Solian and preventive measures undertaken.
Solian 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 Solian therapy.
Amisulpride may increase prolactin levels. Cases of benign pituitary tumours 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 tumour (such as visual field defect and headache), pituitary imaging should be performed. If the diagnosis of pituitary tumour is confirmed, the treatment with amisulpride must be stopped (see section 4.3).
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including Solian. 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.
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).
Reciprocal antagonism of effects between levodopa and neuroleptics. Amisulpride may oppose the effect of dopamine agonists e.g. bromocriptine, ropinirole.
Solian may enhance the central effects of alcohol.
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 (see section 5.3).
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 Solian) 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 (see section 4.8). 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.
A decrease in fertility linked to the pharmacological effects of the drug (prolactin-mediated effect) was observed in treated animals.
Even used as recommended, Solian may cause somnolence and blurred vision so that the ability to drive vehicles or operate machinery can be impaired (see section 4.8).
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).
Uncommon: leukopenia, neutropenia (see section 4.4)
Rare: agranulocytosis (see section 4.4)
Uncommon: allergic reaction
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 (see sections 4.3 and 4.4)
Uncommon: hyperglycaemia (see section 4.4), hypertriglyceridemia and hypercholesterolaemia
Rare: hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Common: insomnia, anxiety, agitation, orgasmic dysfunction
Uncommon: confusion
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 (see section 4.4), which is a potentially fatal complication
Not known: restless legs syndrome
Common: blurred vision (see section 4.7)
Uncommon: bradycardia
Rare: QT interval prolongation, ventricular arrhythmias such as torsade de pointes, ventricular tachycardia, ventricular fibrillation, cardiac arrest, sudden death (see section 4.4).
Common: hypotension
Uncommon: increase in blood pressure
Rare: venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section 4.4).
Uncommon: nasal congestion, pneumonia aspiration (mainly in association with other antipsychotics and CNS depressants).
Common: constipation, nausea, vomiting, dry mouth
Uncommon: hepatocellular injury
Rare: angioedema, urticaria
Not known: photosensitivity reaction
Uncommon: osteopenia, osteoporosis
Uncommon: urinary retention
Not known: drug withdrawal syndrome neonatal (see section 4.6)
Common: weight gain
Uncommon: elevations of hepatic enzymes, mainly transaminases
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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