Limipranil - instructions for use, dose, side effects, contraindications

Active substanceAmisulprideAmisulpride

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Limipranil

pills inwards

AKTAVIS GROUP, AO Iceland

Limipranil

pills inwards

AKTAVIS GROUP, AO Iceland

Solian®

solution inwards

Sanofi-Aventis France France

Solian®

pills inwards

Sanofi-Aventis France France

Dosage form: & nbsppills

Composition:

1 tablet of 50 mg contains:

active substance: amisulpride 50 mg;

Excipients: corn starch 15.0 mg, lactose monohydrate 49.375 mg, methylcellulose 400 cp 2,625 mg, silicon dioxide colloid 2.0 mg, magnesium stearate 1.0 mg.

1 tablet of 100 mg contains:

active substance: amisulpride 100 mg;

Excipients: corn starch 30.0 mg, lactose monohydrate 98.750 mg, methylcellulose 400 cp 5,250 mg, silicon dioxide colloid 4.0 mg, magnesium stearate 2.0 mg.

1 tablet 200 mg contains:

active substance: amisulpride 200 mg;

Excipients: corn starch 60.0 mg, lactose monohydrate 197.5 mg, methylcellulose 400 cp 10.5 mg, silicon dioxide colloid 8.0 mg, magnesium stearate 4.0 mg.

Description:

Tablets 50 mg: round tablets white or almost white with a risk on one side and the inscription "C" on one side and "AK" on the other.

Tablets 100 mg: Round tablets of white or almost white color with a risk and inscriptions "C" and "AL" one side.

Tablets 200 mg: round tablets white or almost white with a risk and inscriptions "C" X and "AM" on the one hand.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.L.05 Amisulpride

Pharmacodynamics:

Amisulpride selectively binds to subtypes with high affinity D2/D3 dopaminergic receptors, while it does not have an affinity for subtypes 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 in high doses,which is due to the blockade of postsynaptic dopamine receptors, and its efficacy against negative symptoms in 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 concentration in the plasma, respectively, is 39 ± 3 and 54 ± 4 ng / ml, 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.The half-life (T1 / 2) of 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 diet (containing 68% of the fluid) reliably 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: delirium, hallucinations, thinking disorders) and / or negative (for example: affective flattening, lack of emotionality and avoiding communication) disorders, including patients with a predominance of negative symptoms.

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.

For patients with a predominance of negative symptoms, an oral dose of 50 to 300 mg per day is recommended. The choice of doses should be individual.

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

Elderly 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. These include drowsiness and sedation, coma, 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 such as "pirouette":

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-releasing 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, muscle stiffness, peripheral nervous system dysfunction, and elevated creatinine phosphokinase levels may develop. 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 the case of serious impairment of kidney function, the dose should be reduced and therapy regimens used,described in the section "Dosage and route of administration".

Since there is no experience of using the drug in patients with severe forms of kidney disorders (QC ≤ 10 ml / min), special care 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 serious ventricular arrhythmias, and it increases in the presence of bradycardia, hypokalemia, congenital or acquired interval extension QT.

Prior to prescribing the drug, and during the treatment period, depending on the clinical status of the patient, it is recommended to monitor factors that may contribute to the development of this rhythm disturbance:

- bradycardia below 55 beats / m in,

- hypokalemia,

- congenital lengthening interval QT,

- simultaneous use of drugs that can cause 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:

Tablets 50 mg, 100 mg and 200 mg.

Packaging:

For 10 tablets in a blister of PVC / Aluminum foil. For 1, 2, 3 or 5 blisters with instructions for use in a cardboard box.

For 20, 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-010254/08

Date of registration:19.12.2008

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

Illustrated instructions

Instructions

Limipranil (Lymipranil)