Limipranil (Lymipranil)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAmisulprideAmisulpride
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  • Limipranil
    pills inwards 
    AKTAVIS GROUP, AO     Iceland
  • Limipranil
    pills inwards 
    AKTAVIS GROUP, AO     Iceland
  • Solian®
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    Sanofi-Aventis France     France
  • Solian®
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    Sanofi-Aventis France     France
    • Dosage form: & nbspfilm coated tablets
    Composition:

    Active substance: amisulpride 400 mg;

    Excipients: lactose monohydrate 200 mg, methyl cellulose 400 cp 20 mg, magnesium stearate 10.5 mg, sodium carboxymethyl starch 49 mg, microcrystalline cellulose 20.5 mg;

    film sheath: methyl methacrylate, dimethylaminoethyl methacrylate, and butyl methacrylate copolymer (Eudragit E 100) 1.5 mg; titanium dioxide (E 171) 0.165 mg, talc 0.42 mg, magnesium stearate 0.15 mg, macrogol 6000 0.075 mg.

    Description:

    Oval biconvex tablets white or almost white, film-coated, with a risk.

    Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)
    ATX: & nbsp

    N.05.A.L.05   Amisulpride

    Pharmacodynamics:

    Amisulpride selectively binds with high affinity to subtypes of D2/ D3 dopaminergic receptors, while it does not have an affinity for the subtypes of D1, D4 and D5.

    Unlike classical and atypical antipsychotics, amisulpride has no affinity for the receptors of serotonin, histamine H1, alpha-adrenergic and cholinergic receptors. Also, amisulpride does not bind to sigma-sites.

    When used in high doses, it blocks the postsynaptic D2 receptors localized in limbic structures (does not affect analogous receptors in the striatum). Does not cause catalepsy and does not lead to hypersensitivity D2- dopamine receptors after repeated treatment.

    In low doses, it predominantly blocks presynaptic D2/ D3 receptors, causing the release of dopamine, responsible for its disinhibitory effects.

    Such an atypical pharmacological profile can serve as an explanation for the antipsychotic effect of amisulpride at high doses that results from the blockade of postsynaptic dopamine receptors and its efficacy against negative symptoms at low doses as a result of the blockade of presynaptic dopamine receptors.

    Besides, amisulpride to a lesser extent, extrapyramidal side effects, which may be due to its predominant limbic activity.

    In patients with schizophrenia with acute attacks amisulpride It acts both on secondary negative symptoms and on affective symptoms, such as depressive mood and retardation.

    Pharmacokinetics:

    Amisulpride has two absorption peaks: one is achieved quickly, one hour after the dose, and the second is between 3 and 4 hours after administration. The plasma concentration is 39 ± 3 and 54 ± 4 ng / ml, respectively, after taking 50 mg.

    The volume of distribution is 5.8 l / kg. Since binding to plasma proteins is low (16%), interaction with other drugs is unlikely.

    Absolute bioavailability is 48%. Amisulpride is metabolized poorly (about 4%), two inactive metabolites are identified. Cumulation of amisulpride does not occur, and its pharmacokinetics remains unchanged after taking repeated doses. Half-life (T1/2) amisulpride is approximately 12 hours after taking the oral dose.

    Amisulpride is excreted unchanged in urine. Kidney clearance is approximately 20 l / h or 330 ml / min.

    A carbohydrate-rich food (containing 68% of the liquid) significantly reduces AUC (the area under the concentration / time curve), the time to reach the maximum concentration, and the maximum concentration of amisulpride, but there was no change in pharmacokinetics after fatty food intake. However, the importance of these observations in everyday clinical practice is unknown.

    Indications:

    Treatment of acute and chronic schizophrenia, accompanied by pronounced productive (for example, delusions, hallucinations, thinking disorders) and / or negative (for example: affective flattening, lack of emotionality and avoiding communication) disorders, including patients with a predominant negative symptom.

    Contraindications:

    - Hypersensitivity to the active ingredient or to other components of the drug;

    - associated prolactin-dependent tumors, for example: prolactinoma of the pituitary gland and breast cancer;

    - pheochromocytoma;

    - children's age (up to 15 years);

    - pregnancy, breast-feeding;

    - women of childbearing age who do not use adequate contraception;

    - combination with the following drugs that can contribute to the development of atrial fibrillation:

    - antiarrhythmic drugs 1a class - quinidine, disopyramide, procainamide;

    - antiarrhythmic medicines class III - amiodarone, sotalol;

    - other drugs - bepridil, cisapride, sultopride, thioridazine, erythromycin (for intravenous administration), wincamine (for intravenous administration), halofantrine, pentamidine, sparfloxacin;

    - combination with levodopa;

    (see section "Interaction with other drugs")

    Carefully:Epilepsy, Parkinsonism, old age, kidney failure.
    Pregnancy and lactation:

    Safety of amisulpride during pregnancy is not established. Therefore, the use of the drug in pregnancy is not recommended, except when the benefits justify the potential risk. It is not known whether the amisulpride in breast milk, so breastfeeding during treatment is contraindicated.

    Dosing and Administration:

    In acute psychotic episodes, oral administration at a dose of 400 to 800 mg per day is recommended. In some cases, the daily dose may be increased to 1200 mg per day. Doses should be increased to reflect individual tolerability.

    The safety of doses exceeding 1200 mg per day has not been adequately investigated, so they should not be used.

    For patients with mixed negative and productive symptoms, doses should be selected to provide optimal control over productive symptoms. Supportive treatment should be set individually at the level of minimum effective doses.

    The choice of doses should be individual.

    In doses exceeding 400 mg per day, Limipranil should be given in 2 divided doses.

    Older patients: Limipranil should be administered with special precautions because of the possible development of arterial hypotension or excessive sedation.

    Renal insufficiency:

    Excretion of limipranil is carried out through the kidneys. In case of renal insufficiency, the dose for patients with creatinine clearance (CK) of 30-60 ml / min should be reduced by half and up to 1/3 for patients with SC from 10 to 30 ml / min.

    Side effects:

    Frequent side effects (5 - 10%): insomnia, anxiety, agitation.

    Less frequent side effects (0.1-5%): drowsiness, gastrointestinal disorders such as constipation, nausea, vomiting, dry mouth.

    Like other antipsychotics amisulpride causes an increase in the level of prolactin in the blood plasma, which returns to the previous value after the drug is discontinued. This can cause galactorrhea, amenorrhea, gynecomastia, chest pain, impotence, and weight gain.

    Can develop acute dystonia (spasmodic torticollis, oculogic crises, trismus). This condition is reversible and is corrected with the help of antiparkinsonian means.The incidence of extrapyramidal symptoms (tremor, hypertension, hypersalivation, akathisia, hypokinesia) that depend on the dose remains very low in the treatment of patients with a prevalence of negative symptoms at doses of 50-300 mg / day.

    Reports of late dyskinesia, characterized by rhythmic, involuntary movements of predominantly language and / or face, usually refer to cases of prolonged use of the drug. Antiparkinsonian drugs are ineffective, they can cause worsening of symptoms.

    In rare cases, it is possible to develop arterial hypotension and bradycardia, as well as lengthening the interval QT, very rarely - atrial fibrillation.

    Occasionally reported on allergic reactions, increased levels of liver enzymes, mainly transaminases and cases of convulsive seizures.

    There are very rare reports of cases of malignant neuroleptic syndrome (see "Special instructions").

    Overdose:

    The experience associated with an overdose of amisulpride is limited. It is reported on the enhancement of known pharmacological effects of the drug. They include drowsiness and sedation, to whom,arterial hypotension and extrapyramidal symptoms.

    In cases of acute overdose, the possibility of interaction of several drugs should be assumed.

    There is no specific antidote for amisulpride. Treatment is symptomatic, strict monitoring of vital functions of the body is recommended and continuous monitoring of the condition of the heart (the risk of lengthening the interval QT) before the patient's recovery. Hemodialysis is not effective.

    In case of serious extrapyramidal symptoms, anticholinergics should be prescribed.

    Interaction:

    CONTRAINDICATED COMBINATIONS

    Combinations that can cause ventricular arrhythmia of the "pirouette" type:

    - Antiarrhythmic drugs 1a class, such as quinidine, disopyramide.

    - Antiarrhythmic drugs of the III class, such as amiodarone, sotalol.

    - Other drugs, such as bepridil, cisapride, sultopride, thioridazine, intravenous erythromycin, intravenous wincamine, halofantrine, pentamidine, sparfloxacin.

    Levodopa: mutual antagonism of the action of levodopa and neuroleptics.

    NOT RECOMMENDED COMBINATIONS

    Amisulpride enhances the inhibitory effect on the central nervous system alcohol.

    COMBINATIONS REQUIRING A SPECIAL CAUTION

    Drugs that increase the risk of ventricular arrhythmia of the type

    Drugs that cause bradycardia, such as beta-blockers; calcium channel blockers that cause bradycardia (diltiazem and verapamil); clonidine, guanfacine, preparations of digitalis.

    Drugs that can cause hypokalemia: potassium-withdrawing diuretics, laxatives, amphotericin B, glucocorticoids, tetracosactides (hypokalemia should be adjusted).

    Neuroleptics, such as pimozide, haloperidol; antidepressants such as imipramine; lithium.

    COMBINATIONS TO BE TAKEN INTO ATTENTION

    Combination with drugs that depress the function of the central nervous system, including narcotic analgesics, antipsychotic drugs (antipsychotics), antihistamines with sedative effect, barbiturates, benzodiazepines and other anxiolytic drugs, markedly increasing oppressive effect. With antihypertensive drugs - increased antihypertensive action.

    Special instructions:

    As with other neuroleptics, a malignant neuroleptic syndrome characterized by hyperthermia may develop,rigidity of muscles, dysfunction of the peripheral nervous system, elevated level of creatinine phosphokinase. With the development of hyperthermia, especially when high doses are used, all antipsychotics, including Limipranil, should be discontinued. Limipranil is excreted by the kidneys. In case of serious impairment of kidney function, the dose should be reduced and the therapy regimens described in the section "Dosage and route of administration" should be used.

    Since there is no experience of using the drug in patients with severe forms of renal disorders (CC <10 ml / min), special caution is required in their case.

    Since the drug is poorly metabolized, there is no need to reduce the dose in case of violations of the liver function.

    Limipranil may reduce the convulsive threshold. Therefore, patients with epilepsy in a history require continuous monitoring during therapy with Limipranil.

    In the elderly, Limipranil, like other antipsychotics, should be used with special precautions because of the possible risk of hypotension or excessive sedation.

    In Parkinson's disease, with the appointment of antidopaminergic drugs and Limipranil, care should be taken because of possible deterioration of the condition.Limipranil should be used only if neuroleptic therapy can not be avoided.

    Interval prolongation QT:

    Limipranil causes dose-dependent prolongation of the interval QT. It is known that this effect increases the risk of developing serious ventricular arrhythmias, and it increases in the presence of bradycardia, hypokalemia, congenital or acquired lengthening of the interval QT.

    Prior to the appointment of the drug and during the treatment, depending on the clinical status of the patient, it is recommended to control the factors that can contribute to the development of this rhythm disturbance:

    - bradycardia below 55 beats mines,

    - hypokalemia,

    - congenital elongation interval OT,

    - simultaneous use of drugs capable of causing pronounced bradycardia (<55 bpm), hypokalemia, decreased conduction or lengthening of the interval QT (see section "Interactions with other drugs").

    Effect on the ability to drive transp. cf. and fur:

    Amisulpride affects the reaction rate, so that the ability to drive vehicles or work with machinery can be weakened.

    Form release / dosage:

    Film-coated tablets 400 mg.

    Packaging:

    For 10 tablets in a blister of PVC / Aluminum foil. By 3, 6 or 10 blisters with instructions for use in a cardboard box.

    By 20, 40, 50 or 100 blisters together with instructions for use in a cardboard box (for hospitals).
    Storage conditions:

    At a temperature of no higher than 30 ° C.

    Keep out of the reach of children!

    Shelf life:

    3 years. Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-009316/08
    Date of registration:25.11.2008
    Expiration Date:Unlimited
    The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland
    Manufacturer: & nbsp
    RIVOPHARM, S.A. Switzerland
    Representation: & nbspACTAVIS GROUP AO ACTAVIS GROUP AO Iceland
    Information update date: & nbsp25.02.2018
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