Each tablet contains 100 mg and 400 mg of amisulpride.
Solian 100 mg White to off-white, round, flat faced breakable tablet, weighing approximately 240 mg, engraved AMI 100 on one face and with a breakable bar on the other face.
Solian 400 mg White, film-coated, breakable oblong tablet, engraved AMI 400, weighing approximately 710 mg.
Excipients/Inactive Ingredients: Sodium starch glycolate, lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.
Pharmacology: Pharmacodynamics: Antipsychotic (N: Central Nervous System).
Amisulpride is an antipsychotic in the class of substituted benzamides.
Its pharmacodynamic profile is characterized by selective and predominant affinity for D2 and D3 dopaminergic receptors in the limbic system. Amisulpride has no affinity for serotonergic receptors or other neuroreceptors of histamine, cholinergic or adrenergic types.
During animal studies, high dose of amisulpride preferentially blocked the dopaminergic neurons of the mesolimbic system, when compared with the striatal system. The specific affinity may explain the antipsychotic effects of amisulpride which predominate over its extrapyramidal effects.
At low doses, amisulpride preferentially blocks presynaptic D2/D3 dopaminergic receptors, which may explain its action on negative symptoms.
In a double-blind controlled study versus haloperidol, including 191 patients with acute schizophrenia, the use of amisulpride was associated with an improvement in secondary negative symptoms which was significantly superior to that seen with the comparator.
Pharmacokinetics: In man, amisulpride exhibits two peaks of absorption: The first is reached rapidly, one hour after dosing, and the second is reached three or four hours after administration.
The corresponding plasma levels are 39±3 and 54±4 ng/mL, respectively, following the administration of a 50 mg dose.
The distribution volume is 5.8 L/kg. Plasma protein binding is week (16%) and no drug interactions are anticipated with respect to binding on these proteins. The absolute bioavailability is 48%.
Amisulpride is weakly metabolized: Two inactive metabolites have been identified and represent 4% of the total quantity excreted.
Amisulpride does not accumulate after repeated doses, nor are the pharmacokinetic parameters modified.
The elimination half-life is approximately 12 hours after oral administration.
Amisulpride is excreted in an unchanged form in the urine. 50% of the dose administered via the IV route is excreted in the urine, mainly during the first 24 hours (90% of urinary excretion).
Renal clearance reaches approximately 330 mL/minute.
A meal with a high glucide content significantly reduces the AUC, Tmax and Cmax values of amisulpride, while a meal with a high fat content does not modify these parameters. The influence of these results during amisulpride therapy is unknown.
Liver Insufficiency: Amisulpride being weakly metabolized, a reduction in dosage is not necessary in patient with liver insufficiency.
Renal Insufficiency: The elimination half-life is not modified in patients with renal insufficiency, although total clearance is reduced by a factor of 2.5 to 3.
The AUC of amisulpride is double in patients suffering from mild renal insufficiency, and is nearly 10 times greater in the case of moderate renal insufficiency.
The experiment is however limited in this respect and no data are available for doses higher than 50 mg.
Amisulpride is weakly dialyzable.
Elderly Subjects: The pharmacokinetic data available regarding elderly subjects over the age of 65 years show a 10 to 30 % increase in Cmax, T½ and AUC values following a single dose of 50 mg.
No data are available following repeated dose.
Toxicology: Pre-Clinical Safety Data: The toxicological profile of amisulpride is dominated by the pharmacological effects of the compound. No target organ seems to have been revealed by toxicity studies following repeated doses. The compound is devoid of teratogenic and genotoxic potential. Studies of carcinogenesis have demonstrated hormone-dependent tumours in rhodents. These have no clinical relevance in man.
Solian is indicated for the treatment of psychoses, particularly acute or chronic schizophrenic disorders characterized by positive symptoms (such as delirium, hallucinations, cognitive disorders) and/or negative symptoms (such as dulling of the emotions, emotional and social withdrawal), including when negative symptoms predominate.
As a general rule, if the daily dose is ≤400 mg, amisulpride is administered in a single intake; above a daily dose of 400 mg, it should be divided into two intakes per day.
Predominant Negative Episodes: The recommended dosage is 50 to 300 mg/day. Dosage should be adjusted individually. The optimum dosage is around 100 mg/day.
Mixed Episodes with Positive and Negative Symptoms: At the initiation of the treatment, the dosage should be that which permits control of the positive symptoms i.e., 400 to 800 mg/day. Thereafter, the dosage should be adjusted individually according to the patient’s response, so as to obtain the minimum effective dose.
Acute Psychotic Episodes: At the beginning of treatment, it is possible to start using the IM route for few days at a maximum dose of 400 mg/day, with follow-on treatment by the oral route.
The recommended dosage via the oral route is 400 to 800 mg; the maximum dosage should not exceed 1200 mg.
Thereafter, the dosage is maintained or adjusted, depending on the patient's response.
In all cases, the dosage for maintenance treatment should be fixed individually at the minimum effective dose.
Renal Insufficiency: Because of the renal excretion of amisulpride, the dosage in patient with renal insufficiency should be reduced by half in patients with a creatinine clearance (CrCl) is between 30 and 60 mL/minute, and by a third in those whose creatinine clearance is between 10 and 30 mL/minute.
In the absence of specific data, the use of amisulpride is contraindicated in patients presenting with severe renal insufficiency (CrCl <10 mL/minute) (see Contraindications).
Hepatic Insufficiency: Amisulpride being weakly metabolized, a reduction in dosage is not necessary in patients with hepatic insufficiency.
To date, the data concerning acute overdose with Solian are limited. The signs and symptoms which have been reported usually resulted from an increase in the pharmacological effects of the drug, with the following clinical consequences: Drowsiness, sedation, hypotension, extrapyramidal symptoms and coma.
Fatal outcomes have been reported mainly in combination with other psychotropic agents.
No specific antidote to amisulpride is known. In the event of acute overdose, any combination with other drugs should be established and appropriate measures implemented: Close monitoring of the vital functions.
Cardiac monitoring (risk of a prolongation of the QT interval), which should be pursued until the patients recovers.
If severe extrapyramidal symptoms occur, anticholinergic treatment should be administered.
Amisulpride is weakly dialyzable.
Know hypersensitivity to any component of the product.
Serious hypertensive accidents have been reported in patients with pheochromocytoma receiving anti-dopaminergic drugs, including certain benzamides.
It is therefore wise to abstain from prescribing this product in patients with known or suspected pheochromocytoma.
Children below the age of 15 years, in the absence of clinical data concerning this age group.
Concomitant prolactin-dependent tumor, e.g., prolactin-secreting pituitary adenoma and breast cancer (see Warnings, Precautions and Adverse Reactions).
Severe renal insufficiency (CrCl <10 mL/minute).
Combination with the following medications which could induce Torsade de pointes: Class Ia antiarrhythmic agents such as quinidine, disopyramide. Class III antiarrhythmic agents such as amiodarone, sotalol.
Other medications such as bepridril, cisapride, sultopride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin (see Interactions).
Combination with levodopa (see Interactions).
As with other neuroleptics, neuroleptic malignant syndrome, a potentially fatal complication, characterized by hyperthermia, muscle rigidity, autonomic instability and elevation of CPK creatine phosphokinase may occur. In the event of hyperthermia particularly with high daily doses, all antipsychotic drugs including amisulpride should be discontinued.
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.
Prolongation of the QT Interval: Amisulpride prolongs the QT interval in a dose-dependent way. This effect is known to potentiate the risk of serious ventricular arrhythmias such as Torsade de pointes, is enhanced by the existence of bradycardia, hypokaliaemia, congenital or acquired long QT interval (combination with a drug increasing the QTc interval).
If the clinical status so permits, it is necessary to verify the absence of factors which may flavour the onset of the arrhythmia before any administration: Bradycardia slower than 55 bpm.
Electrolyte imbalance, in particular hypokaliaemia.
Congenital prolongation of the QT interval.
Current treatment with a drug likely to cause marked bradycardia (<55 bpm), hypokaliaemia, slowing of intracardiac conduction or prolongation of the QTc interval.
An ECG is recommended as part of the initial assessment of patients who are receive long-term neuroleptic therapy.
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. Amisulpride should be used with caution in patients with stroke risk factors.
Elderly Patients with Dementia: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 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.
Venous Thromboembolism: Cases of venous thromboembolism, sometimes fatal, have been reported with antipsychotic drugs. Therefore, Amisulpride should be used with caution in patients with risk factors for thromboembolism (see Adverse Reactions).
Breast Cancer: 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.
Benign Pituitary Tumour: Amisulpride may increase prolactin levels. Cases of benign pituitary tumours such as prolactinoma have been observed during amisulpride therapy. (See Adverse Reactions). 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 Contraindications).
Because of the renal excretion of this product, a reduction in dosage is recommended in patients with renal insufficiency (see Dosage & Administration). No data are available concerning patients with severe renal insufficiency (see Contraindications).
Neuroleptics are known to lower the epileptogenic threshold. Patients with a history of convulsive attacks should therefore be monitored closely during treatment with Solian.
Caution should be exercised in elderly subjects, because of their high sensitivity (sedation and hypotension).
Caution should be exercised in patient with Parkinson's disease, in whom this product should only be used if neuroleptic therapy is absolutely necessary.
Hyperglycemia 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 started on amisulpride, should get appropriate glycemic monitoring.
Withdrawal symptoms have been described after abrupt cessation of high therapeutic dose 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.
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including amisulpride. Unexplained infections or fever may be evidence of blood dyscrasia (see Adverse Reactions), and requires immediate haematological investigation.
Effects on the Ability to Drive and Operate Machinery: Drivers and machine operators, in particular are warned of the risks of drowsiness attached to the use of this drug.
Pregnancy: Animal studies have not demonstrated any teratogenic effect. In the absence of any teratogenic effect in animal, a malformative effect in humans is not expected. Indeed, to date substances responsible for malformations in humans have proved to be teratogenic in animals during well-conducted clinical studies in two species.
In clinical use, no relevant data are available at present to assess any malformative or foetotoxic effect of amisulpride when it is administered during pregnancy.
Use of the drug is not recommended during pregnancy 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 (see Adverse Reactions). There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.
Lactation: In the absence of data concerning the passage into breast milk, breast-feeding is contraindicated.
The following CIOMS frequency rating is used, when applicable: Very common ≥10%; Common ≥1 and <10%; Uncommon ≥0.1 and <1%; Rare ≥0.01 and <0.1%; Very rare <0.01%, Unknown (cannot be estimated from available data).
Clinical Trials Data:
Nervous System Disorder: 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.
Common: Acute dystonia (spasm torticollis, oculogyric crisis, trismus) may appear. This is reversible without discontinuation of amisulpride upon treatment with an parkinsontonian agent. Somnolence.
Uncommon: 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. Seizures.
Psychiatric Disorders: Common: Insomnia, anxiety, agitation, orgasmic dysfunction.
Gastrointestinal Disorders: Common: Constipation, nausea, vomiting, dry mouth.
Endrocrine Disorder: 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.
Frequency Not Known: Benign pituitary tumour such as prolactinoma (see Contraindications, Warnings and Precautions).
Metabolism and Nutrition Disorders: Uncommon: Hyperglycemia (see Precautions).
Frequency Not Known: Hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Cardiovascular Disorders: Common: Hypotension.
Investigations: Common: Weight gain.
Uncommon: Elevations of hepatic enzymes, mainly transaminases.
Immune System Disorders: Uncommon: Allergic reaction.
Blood and Lymphatic System Disorders: Frequency Not Known: Leukopenia, neutropenia and agranulocytosis (see Precautions).
Metabolism and Nutrition Disorders: Frequency not known: Hypertriglyceridemia and hypercholesterolemia.
Psychiatric Disorders: Frequency not known: Confusion.
Nervous System Disorders: Frequency not known: Neuroleptic Malignant Syndrome (see Warnings), which is a potentially fatal complication.
Cardiac Disorders: Frequency not known: QT interval prolongation and ventricular arrhythmias such as Torsade de pointes, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest, sudden death (see Warnings).
Vascular Disorders: Frequency not known: Venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see Warnings).
Skin and Subcutaneous Tissue Disorders: Frequency Not Known: Angioedema, urticaria.
Pregnancy, Puerperium and Perinatal Conditions: Frequency not known: Drug withdrawal syndrome neonatal (see Pregnancy under Use in Pregnancy & Lactation).
Contraindicated Combination: Levodopa: Reciprocal antagonism of levodopa and neuroleptics. In the event of extrapyramidal syndrome induced by the neuroleptic, do not treat with levodopa (the dopaminergic receptors are blocked by neuroleptics) but instead use an anticholinergic.
In patients with Parkinson’s disease treated with levodopa and who require treatment with neuroleptics, the pursuit of dopamine therapy is illogical since it aggravates the psychotic disorders and cannot act on the receptors blocked by neuroleptics.
Medications which could induce Torsade de pointes: Class Ia antiarrhythmic agents such as quinidine, disopyramide.
Class III antiarrhythmic agents such as amiodarone, sotalol. Others medications such as bepridril, cisapride, sultopride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin.
Combinations Not Recommended: Alcohol: Alcohol enhances the sedative effect of neuroleptics. Impaired alertness may render driving and machine operation dangerous. Avoid the consumption of alcohol drinks and drugs containing alcohol.
Medications which enhance the risk of Torsade de pointes or could prolong the QT interval.
Bradycardia-inducing medications such as beta-blockers, bradycardia-inducing calcium channel blockers such as diltiazem and verapamil, clonidine guanfacine, digitalics.
Medications which induce hypokaliaemia: Hypokalemic diuretics, stimulant laxatives, IV amphotericin B, glucocorticoids, tetracosactides. Hypokaliaemia should be corrected.
Neuroleptics such as pimozide, haloperidol, imipramine antidepressants, lithium.
Combination to be Taken into Account: Antihypertensive Drugs: Antihypertensive effect and increased risk of orthostatic hypotension (additive effect).
Other Depressants of Central Nervous System: Sedative antidepressants, morphine derivatives (analgesics and antitussives), sedative H1 antihistamines, barbiturates, anxiolytics, clonidine and related substances, hypnotics, methadone, thalidomide.
Enhancement of central depression. Impaired alertness may render driving and machine operation dangerous.
Incompatibilities: None known to date.
Store below 25°C.
Shelf-Life: 3 years.
N05AL05 - amisulpride ; Belongs to the class of benzamides antipsychotics.
Tab 100 mg (white to off-white, round, flat faced, scored) x 3 x 10's. 400 mg (white, film-coated, breakable oblong tablet, engraved AMI 400) x 3 x 10's.