Active ingredients: Amisulpride
SOLIAN 100 mg Tablets
SOLIAN 200 mg Tablets
SOLIAN 400 mg Coated tablets
Why is Solian used? What is it for?
Pharmacotherapeutic group
Psycholeptic, benzamides.
Therapeutic indications
Solian is indicated for the treatment of acute and chronic psychotic disorders in which positive symptoms (such as delirium, hallucinations, thought disturbances) and / or negative symptoms (such as flattening of affect, emotional and social withdrawal) are prevalent, including patients with by predominant negative symptoms.
Contraindications When Solian should not be used
Hypersensitivity to the active substance or to any of the excipients and to closely related substances.
Concomitance of prolactin-dependent tumors such as pituitary prolactinomas and mammary tumors.
Pheochromocytoma.
Children until puberty.
Pregnancy and breastfeeding. In women of childbearing potential who are not using adequate contraception (see "Special warnings").
Association with the following drugs, for the possible onset of torsades de pointes:
- class Ia antiarrhythmics such as quinidine, disopyramide;
- class III antiarrhythmics such as amiodarone, sotalol;
- other drugs such as bepridil, cisapride, sultopride, thioridazine, i.v. methadone, i.v. erythromycin, i.v vincamine, halofantrine, pentamidine, sparfloxacin (see "Interactions").
Combination with levodopa (see "Interactions").
Precautions for use What you need to know before taking Solian
As in the case of other dopamine antagonists, particular caution is required when prescribing amisulpride in parkinsonian patients, as the drug may cause the disease to worsen. Amisulpride should only be used when neuroleptic treatment cannot be avoided.
Hyperglycaemia has been observed in patients treated with some atypical antipsychotics, including amisulpride. Therefore, patients with a certain diagnosis of diabetes mellitus or with risk factors for diabetes should undergo appropriate glycemic monitoring when on amisulpride therapy.
Amisulpride can lower the seizure threshold. Therefore, patients with a history of epileptic episodes should be closely monitored during therapy with amisulpride.
Amisulpride is eliminated by the kidney. In case of renal insufficiency the dose should be reduced or intermittent treatment may be prescribed (see "Dose, method and time of administration").
As with all neuroleptic drugs, amisulpride should be used with particular caution in elderly patients due to the possible risk of hypotension or sedation. Dosage reduction may also be required in case of renal insufficiency.
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including Solian. Unexplained infections or fever may indicate blood dyscrasia (see "Side Effects"), requiring "immediate haematological investigation.
Interactions Which drugs or foods can modify the effect of Solian
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
When neuroleptics are administered concomitantly with QT prolonging drugs, the risk of developing cardiac arrhythmias increases.
Contraindicated associations
- Drugs capable of causing torsades de pointes: - class Ia antiarrhythmics, such as quinidine, disopyramide; - class III antiarrhythmics, such as amiodarone, sotalol; - other drugs such as bepridil, cisapride, sultopride, thioridazine, i.v. methadone, i.v. erythromycin, i.v vincamine, halofantrine, pentamidine, sparfloxacin.
- Levodopa: Mutual antagonism of the effects between levodopa and neuroleptics. Amisulpride can counteract the effect of dopamine agonists such as bromocriptine and ropinirole.
- Do not administer concomitantly with drugs that cause alterations in electrolytes, such as drugs that cause hypokalaemia such as hypokalemic diuretics, stimulating laxatives, amphotericin B i.v., glucocorticoids, tetracosactides. Hypokalemia must be corrected.
Associations not recommended
- Amisulpride, may increase the central effects of alcohol.
- Drugs that increase the risk of torsades de pointes or can prolong QT: - drugs that induce bradycardia: beta-blockers, calcium channel blockers such as diltiazem and verapamil, clonidine, guanfacine, digitalis - neuroleptics such as pimozide, haloperidol, imipramine antidepressants, lithium - some antihistamines - some antimalarials (for example mefloquine)
Associations to consider carefully
- CNS depressants including narcotics, anesthetics, analgesics, H1 antihistamine sedatives, barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives;
- Antihypertensive drugs and other hypotensive preparations.
Warnings It is important to know that:
As with other neuroleptic drugs, a set of symptoms called Neuroleptic Malignant Syndrome can occur, a potentially fatal complication characterized by hyperthermia, muscle stiffness, autonomic instability and elevated CPK. In case of hyperthermia, particularly when daily doses are high, any antipsychotic drug, including amisulpride, should be discontinued.
Prolongation of the QT interval
Use with caution in patients with cardiovascular disease or a family history of QT prolongation. Avoid concomitant therapy with other neuroleptics. Amisulpride causes dose-dependent prolongation of the QT interval. This effect is known to increase the risk of serious ventricular arrhythmias, such as torsades de pointes.
Before administration and, if possible, depending on the clinical status of the patient, it is recommended to monitor the factors that could favor the onset of this rhythm disturbance, such as:
- bradycardia less than 55 beats per minute;
- electrolyte imbalance, especially hypokalemia;
- congenital or acquired prolonged QT interval;
- ongoing treatment with drugs capable of inducing marked bradycardia (
Cerebrovascular events
An approximately three-fold increase in the risk of cerebrovascular events was observed in randomized clinical trials versus placebo in a population of elderly patients with dementia treated with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk for other antipsychotics or other patient populations cannot be excluded. Solian should be used with caution in patients with stroke risk factors.
Elderly patients with dementia
Increased risk of death in elderly patients with dementia-related psychosis treated with antipsychotic drugs. Analyzes of seventeen placebo-controlled clinical trials (10-week modal duration) in patients who were largely taking atypical antipsychotic drugs revealed a 1.6 to 1 risk of death in patients treated with the drug. 7 times that found in placebo-treated patients. In a 10-week controlled study, the death rate in patients treated with the drug was approximately 4.5%, compared with 2.6% in the placebo group.
Although the causes of death during clinical trials with atypical antipsychotics were varied, most appeared to be either cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia) in nature.
Observational studies suggest that, as with atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may also increase mortality. The extent to which the finding of increased mortality in observational studies can be attributed to antipsychotic drugs rather than to some specific patient characteristics is unclear.
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 must be identified before and during treatment with amisulpride and preventive measures taken.
Breast cancer
Amisulpride may increase prolactin levels. Patients with a personal or family history of breast cancer need to be alerted and monitored during amisulpride therapy.
Withdrawal symptoms, including nausea, vomiting and insomnia, have been described following abrupt discontinuation of high therapeutic doses of antipsychotic drugs. Psychotic symptoms may also recur and development of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported with amisulpride. Therefore, gradual discontinuation of amisulpride is recommended.
Pregnancy, breastfeeding and fertility:
Ask your doctor or pharmacist for advice before taking any medicine. Pregnancy In animals, amisulpride did not show direct toxicity on reproductive function. A decrease in fertility related to the pharmacological effects of the drug (prolactin mediated effect) was observed. No teratogenic effects were observed.
Clinical data on drug exposure in pregnancy are very limited. Therefore, the harmlessness of amisulpride during pregnancy has not been established in humans. Use in pregnancy is not recommended unless the expected benefit justifies the potential risks. If amisulpride is administered during pregnancy, the newborn may experience undesirable drug effects; appropriate monitoring must therefore be considered.
The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics, including Solian, during the last trimester (last three months of pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, breathing problems and difficulty in food intake (see "Side Effects"). If your child shows any of these symptoms, contact your doctor. Breast-feeding It is not known whether amisulpride is excreted in human milk; therefore breastfeeding is contraindicated.
Effects on ability to drive and use machines:
Even when used as recommended, amisulpride may cause drowsiness and thus impair the ability to drive or use machines (see "Side Effects").
Important information about some of the ingredients:
SOLIAN tablets and SOLIAN coated tablets contain lactose monohydrate: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Solian: Dosage
In acute psychotic episodes, doses between 400 and 800 mg / day are recommended. In some patients the daily dose may be increased up to 1200 mg / day. The safety of use of doses higher than 1200 mg / day has not been definitively evaluated; these dosages are therefore not recommended. A progressive increase in the dose is not required at the beginning of treatment with amisulpride. Doses should be adjusted according to individual response.
In patients with mixed positive and negative symptoms, doses should be adjusted to achieve optimal control of positive symptoms. Maintenance therapy should be individually established on the basis of the lowest effective dose.
In patients with predominantly negative symptoms, doses between 50 and 300 mg / day are recommended. Doses should be adjusted according to individual response. Amisulpride can be administered once daily at doses up to 400 mg; for doses of amisulpride above 400 mg the administration must be divided into two daily intakes.
Elderly patients: The safety of amisulpride has been evaluated in a limited number of elderly patients.Amisulpride should be used with particular care due to a possible risk of hypotension and sedation. Dosage reduction may also be required in case of renal insufficiency.
Children: The efficacy and safety of amisulpride from puberty to age 18 have not been established. Limited data are available on the use of amisulpride in adolescents with schizophrenia. Therefore, the use of amisulpride from puberty to age 18 is not recommended. Amisulpride is contraindicated in children up to puberty as its safety has not yet been established. (see "Contraindications").
Renal insufficiency: amisulpride is eliminated by the kidney. In renal insufficiency, the dosage should be reduced to half in patients with creatinine clearance between 30 and 60 ml / min, and to one third in patients with creatinine clearance between 10 and 30 ml / min. is experienced in patients with severe renal insufficiency (creatinine clearance less than 10 ml / min), special caution is recommended in these patients (see "Precautions for use").
Hepatic insufficiency: Dosage reduction should not be necessary as the drug is poorly metabolised.
Overdose What to do if you have taken too much Solian
Experience with amisulpride in overdose is limited. Symptoms of accentuation of the known pharmacological effects of the drug such as somnolence or sedation, hypotension, extrapyramidal symptoms and coma have been reported. Cases with fatal outcome have been reported mainly in combination with other psychotropic agents. .
In case of acute overdose, consideration should be given to the possibility of taking multiple drugs.
Since amisulpride is poorly dialyzable, hemodialysis is not useful to eliminate the drug. There is no specific antidote for amisulpride; therefore adequate supportive measures must be instituted and careful supervision of vital functions is recommended: continuous cardiac monitoring (risk QT interval prolongation) until the patient has stabilized.
In case of severe extrapyramidal symptoms, administer anticholinergic drugs. In case of accidental ingestion / intake of an excessive dose of SOLIAN, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of SOLIAN, ask your doctor or pharmacist.
Side Effects What are the side effects of Solian
Like all medicines, Solian can cause side effects, although not everybody gets them.
The undesirable effects have been sorted into frequency classes, using the following convention: very common (≥ 1/10); common (≥1 / 100,110); uncommon (≥ 1/1000;
Data from Clinical Studies
The following side effects have been observed in controlled clinical trials. It should be noted that in some cases it can be difficult to distinguish adverse events from symptoms of the underlying disease.
Nervous system disorders:
Very common: Extrapyramidal symptoms may appear: tremor, rigidity, hypokinesis, hypersalivation, akathisia, dyskinesia. These symptoms are generally mild at optimal dosages and partially reversible with the administration of antiparkinsonian drugs, even without discontinuation of amisulpride. The dose-related incidence of extrapyramidal symptoms remains extremely low in the treatment of patients with predominantly negative symptoms at doses between 50 and 300 mg / day.
Common: Acute dystonia (spasmodic torticollis, oculogyric crisis, trismus) may occur, which is reversible with the administration of an antiparkinsonian drug, even without discontinuing amisulpride therapy. Drowsiness.
Uncommon: Tardive dyskinesia characterized by rhythmic involuntary movements predominantly involving the tongue and / or face has been reported, usually following prolonged administration of amisulpride. Treatment with antiparkinsonian drugs is ineffective or may induce aggravation of symptoms. Convulsions.
Psychiatric disorders:
Common: Insomnia, anxiety, agitation, psychomotor excitability, orgasm abnormalities.
Frequency not known: Confusion.
Gastrointestinal disorders:
Common: Constipation, nausea, vomiting, dry mouth, dyspepsia.
Endocrine disorders:
Common: Amisulpride causes a reversible increase in plasma prolactin levels after drug discontinuation. This increase may be associated with the onset of galactorrhea, amenorrhea, gynecomastia, mastodynia and erectile dysfunction.
Metabolism and nutrition disorders:
Uncommon: Hyperglycaemia (see section "Precautions for use").
Frequency not known: Hypertriglyceridaemia and hypercholesterolemia.
Cardiac disorders:
Common: Hypotension
Uncommon: Bradycardia and palpitation
Diagnostic tests:
Common: Weight gain
Uncommon: Elevation of liver enzymes, especially transaminases
Immune system disorders:
Uncommon: Allergic reactions
Were also observed: tendency to chills of low intensity, dyspnoea of low intensity, muscle aches.
Post-marketing data
The following adverse reactions were reported as spontaneous reports only:
Disorders of the blood and lymphatic system:
Frequency not known: leukopenia, neutropenia and agranulocytosis (see section "Precautions for use").
Nervous system disorders:
Frequency not known: Neuroleptic Malignant Syndrome, which is a life-threatening complication (see section "Special warnings").
Cardiac disorders:
Frequency not known: QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, which can lead to ventricular fibrillation or cardiac arrest, sudden death (see section "Special warnings").
Vascular disorders:
Frequency not known: Venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section "Special warnings").
Skin and subcutaneous tissue disorders:
Frequency not known: Angioedema, urticaria.
Conditions of pregnancy, puerperium and perinatal conditions:
Frequency not known: neonatal withdrawal syndrome, extrapyramidal symptoms (see section Pregnancy and lactation)
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Italian Medicines Agency, Website: http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicinal.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Special precautions for storage:
Tablets and coated tablets: this medicine does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.
Composition and pharmaceutical form
Composition
Each tablet contains:
Active principle:
SOLIAN 100 mg tablets: amisulpride 100 mg
SOLIAN 200 mg tablets: amisulpride 200 mg
Excipients: sodium carboxymethyl starch (type A), lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.
SOLIAN 400 mg coated tablets:
Each coated tablet contains:
Active ingredient: amisulpride 400 mg
Excipients: sodium starch glycolate (type A), lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.
Tablet coating: hypromellose, microcrystalline cellulose, polyoxyl stearate 40, titanium dioxide (E171).
Pharmaceutical form and packaging:
SOLIAN 100 mg Tablets: 30 Divisible tablets
SOLIAN 200 mg Tablets: 30 Divisible tablets
SOLIAN 400 mg Coated tablets: 30 scored coated tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SOLIAN TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains:
SOLIAN 100 mg TABLETS
Active principle: amisulpride 100 mg
Excipients: lactose monohydrate 69.6 mg
SOLIAN 200 mg TABLETS
Active principle: amisulpride 200 mg
Excipients: lactose monohydrate 139.2 mg
Each coated tablet contains:
SOLIAN 400 mg COATED TABLETS
Active principle: amisulpride 400 mg
Excipients: lactose monohydrate 130.25 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Divisible tablets
Divisible coated tablets
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
• Solian is indicated for the treatment of acute and chronic psychotic disorders in which positive symptoms (such as delirium, hallucination, thought disturbances) and / or negative symptoms (such as flattening of affect, emotional and social withdrawal) are prevalent, including patients characterized by predominant negative symptoms.
04.2 Posology and method of administration
• In acute psychotic episodes, doses between 400 and 800 mg / day are recommended. In some patients the daily dose may be increased up to 1200 mg / day.
The safety of use of doses above 1200 mg / day has not been definitively evaluated; such dosages are therefore not recommended. A progressive increase in dose is not required at the start of treatment with amisulpride. Doses should be adjusted according to individual response.
In patients with mixed positive and negative symptoms, doses should be adjusted to achieve optimal control of positive symptoms.
Maintenance therapy should be individually established on the basis of the lowest effective dose.
• In patients with predominantly negative symptoms (deficit syndrome), doses between 50 and 300 mg / day are recommended. Doses should be adjusted according to individual response.
• Amisulpride can be administered once daily at doses up to 400 mg; for doses of amisulpride above 400 mg the administration must be divided into two daily intakes.
• Elderly patients: The safety of amisulpride has been evaluated in a limited number of elderly patients. Amisulpride should be used with particular care due to a possible risk of hypotension and sedation. Dosage reduction may also be required in case of renal insufficiency.
• Children: The efficacy and safety of amisulpride from puberty to the age of 18 years have not been established. Limited data are available on the use of amisulpride in adolescents with schizophrenia. Therefore, the use of amisulpride from puberty to age 18 is not recommended. Amisulpride is contraindicated in children up to puberty, as its safety has not yet been established (see section 4.3).
• Renal insufficiency: amisulpride is eliminated by the kidney. In renal insufficiency the dosage should be reduced to half in patients with creatinine clearance between 30 and 60 ml / min and to one third in patients with creatinine clearance between 10 and 30 ml / min. As there is no experience in patients with severe renal insufficiency (creatinine clearance less than 10 ml / min) special caution is recommended in these patients (see section 4.4).
• Hepatic insufficiency: Dosage reduction should not be necessary as the drug is poorly metabolised.
04.3 Contraindications
Hypersensitivity to the active substance, or to any of the excipients and to closely related substances.
Concomitance of prolactin-dependent tumors such as pituitary prolactinomas and mammary tumors (see sections 4.4 and 4.8).
Pheochromocytoma.
Children until puberty.
Pregnancy and breastfeeding. In women of childbearing age who do not use adequate contraceptive means. (see section 4.6).
Association with the following drugs, for the possible onset of torsades de pointes:
- class Ia antiarrhythmics such as quinidine, disopyramide;
- class III antiarrhythmics such as amiodarone, sotalol;
- other drugs such as bepridil, cisapride, sultopride, thioridazine, i.v. methadone, i.v. erythromycin, i.v vincamine, halofantrine, pentamidine, sparfloxacin (see section 4.5).
Combination with levodopa (See section 4.5).
04.4 Special warnings and appropriate precautions for use
• As with other neuroleptic drugs, a set of symptoms called neuroleptic malignant syndrome, a potentially fatal complication characterized by hyperthermia, muscle stiffness, autonomic instability and elevated CPK, can occur. In case of hyperthermia, particularly when daily doses are high, any antipsychotic drug, including amisulpride, should be discontinued.
• As in the case of other dopamine antagonists, particular caution is required when prescribing amisulpride in parkinsonian patients, as the drug may cause the disease to worsen. Amisulpride should only be used when neuroleptic treatment cannot be avoided.
• Prolongation of the QT interval
Use with caution in patients with cardiovascular disease or a family history of QT prolongation.
Avoid concomitant therapy with other neuroleptics.
Amisulpride causes dose-dependent prolongation of the QT interval (see section 4.8). This effect is known to increase the risk of serious ventricular arrhythmias, such as torsades de pointes.
Before administration and, if possible, depending on the clinical status of the patient, it is recommended to monitor the factors that could favor the onset of this rhythm disturbance, such as:
• bradycardia less than 55 beats per minute;
• electrolyte imbalance, especially hypokalaemia
• congenital or acquired prolonged QT interval;
• ongoing treatment with drugs capable of inducing marked bradycardia (
• Cerebrovascular events
In randomized clinical trials versus An approximately three-fold increase in the risk of cerebrovascular events was observed in a population of elderly patients with dementia treated with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk for other antipsychotics or other patient populations 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 have an increased risk of death.
Analyzes of seventeen placebo-controlled clinical trials (10-week modal duration) in patients who were largely taking atypical antipsychotic drugs revealed a 1.6 to 1 risk of death in patients treated with the drug. 7 times that found in placebo-treated patients. In a 10-week controlled study, the death rate in patients treated with the drug was approximately 4.5%, compared with 2.6% in the placebo group.
Although the causes of death during clinical trials with atypical antipsychotics were varied, most appeared to be either cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia) in nature.
Observational studies suggest that, as with atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may also increase mortality. The extent to which the finding of increased mortality in observational studies can be attributed to antipsychotic drugs rather than to some specific patient characteristics is unclear.
• 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 must be identified before and during treatment with amisulpride and preventive measures taken (see section 4.8). .
• Hyperglycaemia has been observed in patients treated with some atypical antipsychotics, including amisulpride. Therefore, patients with a certain diagnosis of diabetes mellitus or with risk factors for diabetes should undergo appropriate glycemic monitoring when on amisulpride therapy.
• Amisulpride can lower the seizure threshold. Therefore, patients with a history of epileptic episodes should be closely monitored during therapy with amisulpride.
• Amisulpride is eliminated by the kidney. In case of renal insufficiency the dose should be reduced or intermittent treatment prescribed (see section 4.2).
• As with all neuroleptic drugs, amisulpride should be used with particular caution in elderly patients due to the possible risk of hypotension or sedation. Dosage reduction may also be required in case of renal insufficiency.
• Withdrawal symptoms, including nausea, vomiting and insomnia, have been described after abrupt discontinuation of high therapeutic doses of antipsychotic drugs. Psychotic symptoms may also recur and development of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported with amisulpride. Therefore, gradual discontinuation of amisulpride is recommended.
• Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including Solian. Unexplained infections or fever may indicate blood dyscrasia (see section 4.8), requiring immediate haematological investigation.
• Breast cancer
Amisulpride may increase prolactin levels. Patients with a personal or family history of breast cancer should be alerted and monitored during amisulpride therapy.
• Benign pituitary tumor
Amisulpride may increase prolactin levels. Cases of benign pituitary tumor such as prolactinoma have been observed during therapy with amisulpride (see section 4.8). In case of very high prolactin levels or clinical signs of pituitary tumor (such as visual field and headache), imaging tests of the pituitary should be done. If the diagnosis of pituitary tumor is confirmed, treatment with amisulpride should be discontinued.
SOLIAN tablets and SOLIAN coated tablets contain lactose monohydrate; Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
When neuroleptics are administered concomitantly with QT prolonging drugs, the risk of developing cardiac arrhythmias increases.
Contraindicated associations
• Drugs capable of causing torsades de pointes:
• class Ia antiarrhythmics, such as quinidine, disopyramide;
• class III antiarrhythmics, such as amiodarone, sotalol;
• other medicines such as bepridil, cisapride, sultopride, thioridazine, i.v. methadone, i.v. erythromycin. vincamine i.v., halofantrine, pentamidine, sparfloxacin.
• Levodopa: reciprocal antagonism of the effects between levodopa and neuroleptics. Amisulpride can counteract the effect of dopamine agonists such as bromocriptine and ropinirole.
• Do not administer concomitantly with drugs that cause alterations in electrolytes, such as drugs that cause hypokalaemia such as hypokalemic diuretics, stimulating laxatives, amphotericin B i.v., glucocorticoids, tetracosactides. Hypokalemia must be corrected.
Associations not recommended
• Amisulpride, may increase the central effects of alcohol.
• Drugs that increase the risk of torsades de pointes or can prolong QT:
• drugs that induce bradycardia: beta-blockers, calcium channel blockers such as diltiazem and verapamil, clonidine, guanfacine; digitalis
• neuroleptics such as pimozide, haloperidol, imipramine antidepressants, lithium
• some antihistamines
• some antimalarials (for example mefloquine)
Associations to consider carefully
• CNS depressants including narcotics, anesthetics, analgesics, H1 anti-histamine sedatives, barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives;
• Anti-hypertensive drugs and other hypotensive preparations.
04.6 Pregnancy and lactation
Pregnancy
In animals, amisulpride did not show direct toxicity on reproductive function. A decrease in fertility related to the pharmacological effects of the drug (prolactin mediated effect) was observed. No teratogenic effects were observed.
Clinical data on drug exposure in pregnancy are very limited. Therefore, the safety of amisulpride during pregnancy has not been established in humans. Use in pregnancy is not recommended unless the expected benefit justifies the potential risks.
If amisulpride is administered during pregnancy, the newborn may experience undesirable drug effects; appropriate monitoring must therefore be considered.
Infants exposed to conventional or atypical antipsychotics including Solian during the third trimester of pregnancy are at risk for adverse effects including extrapyramidal or withdrawal symptoms which may vary in severity and duration after birth (see 4.8). There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, food intake disturbances. Infants should therefore be closely monitored.
Feeding time
It is not known whether amisulpride is excreted in human milk; therefore breastfeeding is contraindicated.
04.7 Effects on ability to drive and use machines
Even when used as recommended, amisulpride may cause drowsiness and thus impair the ability to drive or use machines (see section 4.8).
04.8 Undesirable effects
The undesirable effects have been sorted into frequency classes, using the following convention :
very common (≥ 1/10); common (≥ 1/100;
Data from Clinical Studies
The following side effects have been observed in controlled clinical trials. It should be noted that in some cases it can be difficult to distinguish adverse events from symptoms of the underlying disease.
• Nervous system disorders:
Very common: Extrapyramidal symptoms may appear: tremor, rigidity, hypokinesis, hypersalivation, akathisia, dyskinesia. These symptoms are generally mild at optimal dosages and partially reversible with the administration of antiparkinsonian drugs, even without discontinuation of amisulpride. The dose-related incidence of extrapyramidal symptoms remains extremely low in the treatment of patients with predominantly negative symptoms at doses between 50 and 300 mg / day.
Common: Acute dystonia (spasmodic torticollis, oculogyric crisis, trismus) may occur, which is reversible with the administration of an antiparkinsonian drug, even without discontinuing amisulpride therapy.
Drowsiness.
Uncommon: Tardive dyskinesia characterized by rhythmic involuntary movements predominantly involving the tongue and / or face has been reported, usually following prolonged administration of amisulpride. Treatment with antiparkinsonian drugs is ineffective or may induce aggravation of symptoms.
Convulsions.
• Psychiatric disorders:
Common: Insomnia, anxiety, agitation, psychomotor excitability, orgasm abnormalities.
Frequency not known: Confusion.
• Gastrointestinal disorders:
Common: Constipation, nausea, vomiting, dry mouth, dyspepsia.
• Endocrine disorders:
Common: Amisulpride causes reversible increases in plasma prolactin levels after drug discontinuation. This increase may be associated with the onset of galactorrhea, amenorrhea, gynecomastia, mastodynia and erectile dysfunction.
• Metabolism and nutrition disorders:
Uncommon: Hyperglycaemia (see section 4.4)
Frequency not known: Hypertriglyceridaemia and hypercholesterolemia
• Cardiac disorders:
Common: Hypotension
Uncommon: Bradycardia and palpitation
• Diagnostic tests:
Common: Weight gain
Uncommon: Elevation of liver enzymes, especially transaminases
• Disorders of the immune system:
Uncommon: Allergic reactions
Were also observed: tendency to chills of low intensity, dyspnoea of low intensity, muscle aches.
Post-marketing data
The following adverse reactions were reported as spontaneous reports only:
• Disorders of the blood and lymphatic system
Frequency not known: leukopenia, neutropenia and agranulocytosis (see section 4.4).
• Nervous system disorders:
Frequency not known: Neuroleptic Malignant Syndrome, which is a life-threatening complication (see section 4.4).
• Endocrine disorders:
Frequency not known: benign pituitary tumor such as prolactinoma (see sections 4.3 and 4.4)
• Metabolism and nutrition disorders:
Frequency not known: hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• Cardiac disorders:
Frequency not known: QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, which can lead to ventricular fibrillation or cardiac arrest, sudden death (see section 4.4).
• Vascular disorders:
Frequency not known: Venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section 4.4).
• Skin and subcutaneous tissue disorders:
Frequency not known: Angioedema, urticaria.
• Conditions of pregnancy, puerperium and perinatal conditions
Frequency not known: neonatal withdrawal syndrome, extrapyramidal symptoms (see section 4.6).
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the Italian Medicines Agency, Website: http://www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Experience with amisulpride in overdose is limited. Symptoms of accentuation of the known pharmacological effects of the drug such as somnolence or sedation, hypotension, extrapyramidal symptoms and coma have been reported. Cases with fatal outcome have been reported mainly in combination with other psychotropic agents. .
In case of acute overdose, consideration should be given to the possibility of taking multiple drugs. Since amisulpride is poorly dialyzable, hemodialysis is not helpful to eliminate the drug.
There is no specific antidote for amisulpride; therefore adequate supportive measures must be instituted and careful supervision of vital functions is recommended: continuous cardiac monitoring (risk of QT interval prolongation) until the patient is stabilized.
In case of severe extrapyramidal symptoms, administer anticholinergic drugs.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Psycholeptics, benzamides - ATC code: N05AL05
Amisulpride selectively binds with high affinity to human dopamine receptor subtypes D2 / D3, while it is devoid of affinity to the receptor subtypes D1, D4 and D5.
Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonergic, alpha-adrenergic, H1-histaminergic and cholinergic receptors. It also does not bind to sigma sites.
In animals, at high doses, amisulpride preferentially blocks post-synaptic D2 receptors located in limbic structures than those located in the striatum. Unlike classic neuroleptics, it does not induce catalepsy and does not determine hypersensitivity of D2 receptors even after repeated treatments.
At low doses it preferentially blocks the pre-synaptic D2 / D3 receptors, causing the release of dopamine, responsible for the disinhibiting effects of the drug.
This atypical pharmacological profile may explain the antipsychotic effect of amisulpride at higher doses, through the blockade of post-synaptic dopaminergic receptors and its efficacy against negative symptoms, at lower doses, through the blockade of pre-synaptic dopaminergic receptors.
Furthermore, the reduced tendency of amisulpride to induce extrapyramidal side effects may be related to its preferential limbic activity.
In clinical trials including schizophrenic patients with acute exacerbations, SOLIAN significantly improved secondary negative symptoms as well as affective symptoms such as depressed mood and slowing.
05.2 "Pharmacokinetic properties
In humans, amisulpride has two absorption peaks: the first which is reached rapidly one hour after the dose and the second within 3-4 hours after administration. Plasma concentrations are respectively 39 ± 3 and 54 ± 4 ng / ml after a dose of 50 mg.
The volume of distribution is 5.8 l / kg; as plasma protein binding is low (16%) any interactions with other drugs are unlikely.
The absolute bioavailability is 48%. Amisulpride is poorly metabolised; two inactive metabolites have been identified, corresponding to approximately 4% of the dose. After repeated dosing there is no accumulation of amisulpride and the pharmacokinetic properties of the product remain unchanged. amisulpride, after oral administration, is approximately 12 hours.
Amisulpride is excreted via the kidney as unchanged drug. 50% of an intravenous dose is excreted in the urine; 90% of this is eliminated in the first 24 hours. Renal clearance is in the order of 20l / I have 330ml / min.
A meal rich in carbohydrates (with the liquid part equal to 68%) significantly decreases the AUC, Tmax and Cmax of amisulpride, while, after a high-fat meal, no changes in the kinetic parameters described above were observed. .
However, the significance of these findings in routine clinical use is not known.
Hepatic insufficiency: As the drug is poorly metabolised, a reduction in dosage should not be necessary in patients with hepatic insufficiency.
Renal insufficiency: the elimination half-life is unchanged in patients with renal insufficiency but systemic clearance is reduced by 2.5 to 3-fold. In mild renal insufficiency the AUC of amisulpride increases 2-fold, while a 10-fold increase is observed. in moderate renal insufficiency (see section 4.2). However, experience is limited and there are no data at doses higher than 50 mg.
Amisulpride is poorly dialyzed.
Some pharmacokinetic data in elderly patients (> 65 years) show a 10-30% increase in Cmax, T½ and AUC after a single 50 mg dose. No data are available after repeated doses.
05.3 Preclinical safety data
A global evaluation of the tolerability studies indicates that amisulpride does not carry any general, organ-specific, teratogenic, mutagenic or carcinogenic risks. relevant toxicological significance, under the conditions tested.
The maximum tolerated doses in the rat (200 mg / kg / day) and in the dog (120 mg / kg / day) are expressed as AUC, respectively 2 and 7 times higher than the maximum recommended doses in humans.
No carcinogenic risk relevant to humans has been identified in the mouse (up to 120 mg / kg / day) and in the rat (up to 240 mg / kg / day) considering that the dose administered in the rat corresponds to 1.5 - 4. , 5 times the AUC waiting for the man.
Reproductive studies conducted in rats, rabbits and mice show no teratogenic potential.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
SOLIAN 100 mg TABLETS and SOLIAN 200 mg TABLETS:
Excipients:
sodium carboxymethyl starch (type A), lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.
SOLIAN 400 mg COATED TABLETS
Excipients:
starch sodium glycolate (type A), lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.
Tablet coating:
hypromellose, microcrystalline cellulose, polyoxyl stearate 40, titanium dioxide (E171).
06.2 Incompatibility
Not known.
06.3 Period of validity
Tablets and coated tablets: 3 years.
06.4 Special precautions for storage
Tablets and coated tablets: This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Box of 30 divisible tablets in opaque white PVC / All.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
SOLIAN 100 mg TABLETS: AIC n ° 033462019
SOLIAN 200 mg TABLETS: AIC n ° 033462021
SOLIAN 400 mg COATED TABLETS: AIC n ° 033462045
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
SOLIAN 100 mg TABLETS December 1999 / January 2010
SOLIAN 200 mg TABLETS December 1999 / January 2010
SOLIAN 400 mg COATED TABLETS January 2000 / January 2010
10.0 DATE OF REVISION OF THE TEXT
November 2015
