Lerivon® (Lerivon®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceMianserinMianserin
Similar drugsTo uncover
  • Lerivon®
    pills inwards 
    Organon, N.V.     Netherlands
    • Dosage form: & nbsptfilm-covered laths
    Composition:

    1 tablet contains:

    Active substance: mianserin hydrochloride 30 mg.

    Excipients: potato starch 30 mg, silicon dioxide colloidal anhydrous 6 mg. magnesium stearate 0.6-3 mg, methylcellulose 3 mg, calcium hydrophosphate dihydrate up to 300 mg.

    Composition of the film shell: hypromellose about 2.5 mg, macrogol 8000 about 0.5 mg, titanium dioxide (E 171) about 1.0 mg.

    Description:

    White oval biconvex tablets covered with a film sheath, engraved with "CT" above "7" with a dividing line between them on one side, "ORGANON" - on the other.

    Pharmacotherapeutic group:antidepressant
    ATX: & nbsp

    N.06.A.X.03   Mianserin

    Pharmacodynamics:

    Mianserin belongs to the group of piperazino-azepine compounds, which are chemically different from tricyclic antidepressants (TCAs). In its structure, there is no main side chain, which, it is believed, is responsible for the anticholinergic activity of TCAs. Lerivon® enhances noradrenergic transmission in the brain by blocking α2adrenoreceptors and inhibition of norepinephrine reuptake. In addition, interaction with serotonin receptors in the central nervous system was found.Pharmaco-electroencephalographic studies in humans confirmed the antidepressant effect of Lerivon®. Antidepressant effect of Lerivon® was demonstrated in placebo-controlled studies and was similar to the therapeutic effect of other antidepressants currently used.

    The drug Lerivon® is well tolerated by patients with cardiovascular diseases. In therapeutically effective doses, Lerivon® does not have anticholinergic activity and has virtually no effect on the cardiovascular system. Compared with TCAs, it causes less cardiotoxic effects in overdose. Lerivon® is not an antagonist of sympathomimetic and hypotensive agents that interact with adrenergic receptors (eg, betanidine) or α2-adrenoceptors (eg, clonidine, methyldopa).

    The drug Lerivon ® has a sedative effect, causing drowsiness and possible disruption of coordination and rapidity of reactions.

    Pharmacokinetics:

    After ingestion, the active substance of Lerivon®, mianserin. quickly and well absorbed.The maximum concentration in the plasma is reached within 1-3 hours. Bioavailability is about 20%, probably as a result of primary passage through the liver. The binding of myanserin to plasma proteins is about 96%. Half-life (21-61 hours) causes a single daily dose. Equilibrium concentrations in the plasma are reached within 6 days. A high interindividual variation of plasma concentrations in patients, in particular in the elderly, was observed. The relationship between plasma concentration and clinical efficacy has not been established.

    Mianserin is extensively metabolized in the liver with the formation of three metabolites: dysmethylmanserin, 8-hydroxymianserin and mianserin monoxide. In animal studies, the first two metabolites had an antidepressant and sedative effect. Mianserin is mainly excreted by the kidneys in the form of conjugates (64-77% after a once-taken single dose) and through the intestine (8-28%) for 7-9 days, 58% of which is excreted within 24 hours. The major part of the metabolites eliminated by the kidneys is the Quaternary N-glucuronide mianserin.

    There is no data on excretion in breast milk or penetration through the placenta. The main ways of biotransformation are demethylation and oxidation with the subsequent formation of conjugates.

    Indications:Depression of various etiologies.
    Contraindications:
    • Mania.
    • Severe liver dysfunction.
    • Hypersensitivity to mianserin or to any auxiliary substance of the drug.
    • Use in children and adolescents under the age of 18 years.
    • The use of myanserin concurrently with monoamine oxidase (MAO) inhibitors.
    Carefully:

    Hepatic or renal failure, recent acute myocardial infarction, angina pectoris, arrhythmia, heart block, angle-closure glaucoma, prostatic hyperplasia, diabetes mellitus, epilepsy and organic brain damage syndrome, arterial hypotension, elderly age, pheochromacitoma.

    Pregnancy and lactation:

    Experiments on animals and limited data on humans indicate that mianserin does not have an adverse intrauterine or neonatal effect. Mianserin is excreted in mother's milk only in very small quantities.Lerivon® should be used during pregnancy and during breastfeeding only if the possible benefit to the mother justifies the potential risk to the fetus or the baby.

    Dosing and Administration:

    Tablets should be taken orally, if necessary, washed down with water, and swallowed without chewing.

    Adults

    The dosage regimen is determined individually. An initial dose of 30 mg per day is recommended. This dose can be gradually increased every few days to obtain the optimal clinical response. The effective daily dose is usually 60-90 mg.

    Elderly

    The dosage regimen is determined individually. The initial dose should be 30 mg. This dose can be gradually increased every few days. For a satisfactory clinical response, a lower dose may be sufficient than the usual adult dose.

    Children

    Lerivon® should not be used in children and adolescents under the age of 18 (see "Contraindications", "Special instructions").

    - The daily dose can be divided into several doses, or preferably (taking into account the beneficial effect on sleep) be administered as a single dose for overnight administration.

    - When treated with a suitable dose, a positive response to treatment should develop after 2-4 weeks. In case of insufficient response to treatment, the dose may be increased. If after this, after another 2-4 weeks there is no response to treatment, then the drug should be discontinued.

    - It is recommended to continue antidepressant therapy within 4-6 months after the onset of clinical improvement.

    - The abrupt cessation of treatment with Lerivon® in very rare cases causes withdrawal symptoms.

    Side effects:

    Patients with depression exhibit a number of symptoms directly related to the disease itself (dry mouth, persistent constipation, accommodation disorders), so it is sometimes difficult to determine which symptoms are the consequence of the disease and which are the result of treatment with Lerivon®.

    The frequency of the undesirable events listed below is not established.

    Violations of the blood and lymphatic system

    Pathological changes in the circulatory system, usually manifested by granulocytopenia, agranulocytosis, thrombocytopenia or aplastic anemia (see section "Special instructions").

    Disorders from the metabolism and nutrition

    Weight gain.

    Disorders of the psyche

    Hypomania.

    Disturbances from the nervous system

    Sedation effect, which occurs at the beginning of treatment and decreases with the continuation of treatment (lowering the dose usually does not lead to a reduction in sedation, but there is a possibility of reducing antidepressant efficacy), seizures, hyperkinesis (restless leg syndrome), neuroleptic malignant syndrome, aphasia.

    Heart Disease

    Bradycardia (after taking the initial dose), lengthening the interval QT on the electrocardiogram (ECG), ventricular tachycardia as pirouette.

    Vascular disorders

    Hypotension, orthostatic hypotension.

    Disturbances from the liver and bile ducts

    Increased activity of hepatic enzymes, jaundice, hepatitis, a violation of liver function.

    Disturbances from the skin and subcutaneous tissues

    Exanthema.

    Disturbances from musculoskeletal and connective tissue

    Arthralgia, arthritis.

    Common violations

    Edema.

    Violations of the genitals and mammary gland

    Gynecomastia.

    Disorders from the kidneys and urinary tract

    Syndrome of inadequate secretion of antidiuretic hormone.

    In the course of treatment with myanserin, and also shortly thereafter, cases of suicidal thoughts or suicidal behavior were reported (see section "Special instructions").

    Overdose:

    Symptoms

    Symptoms of acute overdose are usually manifested by an increase in the duration of the sedation. Cardiac arrhythmias, seizures, severe hypotension and respiratory depression occur rarely. The literature describes cases of arterial hypertension, sinus tachycardia, bradycardia, vomiting, dizziness and ataxia, constriction or dilatation of the pupil and coma I. Also, cases of lengthening of the interval QT on an electrocardiogram and development of a ventricular tachycardia on type "pirouette". In connection with this, ECG monitoring is necessary.

    Treatment

    There is no specific antidote. In cases of overdose, if possible, you should induce vomiting in the patient, followed by the administration of activated carbon and osmotic laxative (eg sodium sulfate). If you lose consciousness, you must first intubate, then enter Activated carbon and osmotic laxative. Activated carbon can be administered several times in connection with the intestinal-hepatic circulation of mianserin. In regard to vital functions, treatment is symptomatic and supportive. The benefit of washing the stomach is not established.

    Interaction:

    - The drug Lerivon® can enhance the inhibitory effect of alcohol on the central nervous system, and patients should be advised to refrain from drinking alcohol during treatment.

    - Mianserin can not be used concurrently with MAO inhibitors (such as moclobemide, tranylcypromine and linezolid), and also within two weeks after the end of the course of treatment with these medicines. It should also take about two weeks before the patients who had previously taken mianserin, it will be possible to prescribe MAO inhibitors (see section "Contraindications").

    - Lerivon® does not interact with betanidine, clonidine, methyldopa, guanethidine and propranolol (both in combination with hydralazine and without it). Nevertheless, it is recommended to control blood pressure in patients who simultaneously take antihypertensive drugs.

    - When used simultaneously with antiepileptic drugs that are inducers of isoenzyme CYP3A4 (such as phenytoin and carbamazepine), there may be a decrease in the concentration of myanserin in the plasma. Therefore, consideration should be given to the advisability of adjusting the dose of mianserin during or following the concomitant treatment with the aforementioned drugs.

    - As with other antidepressants, Lerivon® may interfere with the metabolism of coumarin derivatives, for example, warfarin, which requires appropriate monitoring.

    - Risk of lengthening the interval QT and / or ventricular arrhythmias (for example, ventricular tachycardia of the type "pirouette") increases with the simultaneous use of myanserin with other drugs that lengthen the interval QT c (eg, some antipsychotics and antibiotics). Therefore, you should carefully study the instructions for the use of other medications used to obtain information about their effect on the interval QTc.

    - Antidepressants can enhance the sedative effect of antipsychotic, hypnotics, sedatives, antihistamines and anxiolytics.It is necessary to reduce the dose of the above medicines when they are used simultaneously with myanserin.

    - Oral contraceptives and barbiturates can induce microsomal liver enzymes and, accordingly, enhance the metabolism of antidepressants.

    - Antidepressants can increase the metabolism of levodopa in the intestine, presumably due to a decrease in peristalsis.

    - When antidepressants are used in combination with thyrotropic drugs, symptoms of hyperthyroidism may appear. In turn, thyrotropic drugs can enhance the effects of antidepressants.

    Special instructions:

    Use in children and adolescents under the age of 18 years

    Lerivon® should not be used in children and adolescents under the age of 18 years. In clinical trials, suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggressiveness, opposition behavior and anger) were more frequently observed among children and adolescents treated with antidepressants compared to those who received a placebo.

    If, on the basis of clinical necessity, a decision is made to perform the treatment, the patient should be carefully monitored for suicidal symptoms.In addition, there are no data on long-term safety in children and adolescents regarding growth, maturation, cognitive and behavioral development.

    Suicide / suicidal thoughts or worsening of the clinical picture

    Depression is characterized by an increased risk of suicidal thoughts, self-harm and suicide (suicidal behavior). This risk persists until a significant remission occurs. Since there may not be improvement in the first few weeks, patients should remain under the direct supervision of a specialist until improvement occurs. The accumulated clinical experience shows that in the early stages of recovery may increase the risk of suicide.

    Patients with a history of suicidal manifestations or with a high degree of suicidal imagination are at greater risk of suicidal thoughts or suicidal attempts, so they should be carefully monitored during treatment. A meta-analysis of the results of placebo-controlled clinical trials on the use of antidepressants in adult patients with mental disorders revealed an increased risk of suicidal behavior in patients in the age group under 25 years taking antidepressants compared to patients receiving placebo.Therefore, in the treatment of antidepressants, patients should be closely monitored, especially those who are at high risk and are at an early stage of treatment, and also after changing the dosage regimen of the drug. Patients, as well as caregivers, should be warned about the need to observe any clinical signs of impairment, suicidal behavior or suicidal thoughts, as well as for unusual behavioral changes and seek immediate medical attention in the event of such symptoms.

    Taking into account the likelihood of suicide, especially at the beginning of treatment, the patient should be given a limited amount of Lerivon® tablets.

    It was reported that during the treatment with Lerivon®, bone marrow suppression was observed, which was usually expressed in the form of granulocytopenia or agranulocytosis. These reactions most often occurred after 4-6 weeks of treatment and were usually reversible upon discontinuation of treatment. They were observed in all age groups, but more often in elderly patients.If a patient experiences fever, pharyngitis, stomatitis, or other signs of infection, treatment should be discontinued and a detailed clinical blood test performed.

    The drug Lerivon®, like other antidepressants, in susceptible subjects with bipolar depressive illness, can cause hypomania. In this case, treatment with Lerivon® should be discontinued.

    In the treatment of patients with hepatic or renal insufficiency, with heart disease, with diabetes mellitus, the usual precautions should be followed and the dose of concomitant therapy should be monitored.

    During post-registration observation of myanserin, the interval elongation was recorded QT and ventricular arrhythmias (including ventricular tachycardia of the "pirouette" type) (see the "Side effect" section). Leryvon® should be used with caution in patients with risk factors for increasing the interval QT/ ventricular tachycardia of the type "pirouette", including congenital syndrome of lengthening interval QT, age over 65, female gender, structural heart disease / left ventricular dysfunction, kidney or liver disease,simultaneous use of drugs that inhibit the metabolism of the drug Lerivon®, and the simultaneous use of other drugs that extend the interval QTc (see section "Interaction with other drugs"). Before starting treatment, hypokalemia and hypomagnesemia should be adjusted. Consideration should be given to repealing LRIVON® or lowering its dose if the interval QTc is> 500 ms or increases by more than 60 ms.

    Patients with closed-angle glaucoma or with symptoms of prostatic hyperplasia should be monitored because of unpredictability of anticholinergic adverse events when treated with Lerivon®.

    In case of jaundice, treatment with the drug should be discontinued.

    In case of seizures, treatment with the drug should be discontinued.

    Application the elderly patients

    Based on limited clinical evidence, older patients were less prone to adverse reactions, such as agitation, confusion, postural hypotension with mianserin than with tricyclic or tetracyclic antidepressants,but any therapy with these drugs should be used with caution in this group of patients.

    Hypomania

    Lerivon®, like other antidepressants, can cause hypomania in susceptible subjects with bipolar depressive illness. In this case, treatment with Lerivon® should be discontinued.

    Surgical interventions

    If surgical intervention is necessary during myanserin therapy, the anesthetist should be informed of the treatment.

    Pheochromocytoma

    Care must be taken when treating patients with pheochromocytoma.

    Epilepsy

    Regular and careful observation is necessary, as well as compliance with the dosing regimen in patients with epilepsy and organic brain damage syndrome. Clinical experience shows that epileptic seizures are rare during treatment with antidepressants. Lerivon® should be used with caution in patients with a history of seizures. Treatment should be discontinued if seizures develop or when the frequency of seizures increases.

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

    Lerivon® may interfere with psychomotor activity during the first few days of treatment. Patients undergoing treatment with Lerivon® should avoid activities that present a potential hazard, such as driving or working with machinery.

    Form release / dosage:

    Film-coated tablets 30 mg.

    Packaging:

    10 tablets per blister of PVC film and aluminum foil. Two blisters with instructions for use are placed in a cardboard box.

    Storage conditions:

    At a temperature of 2-30 ° C, in a dry and dark place.

    Keep out of the reach of children.

    Shelf life:

    5 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N013340 / 01
    Date of registration:25.12.2007 / 12.10.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Organon, N.V.Organon, N.V. Netherlands
    Manufacturer: & nbsp
    ORGANON, N.V. Netherlands
    Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.
    Information update date: & nbsp05.03.2018
    Illustrated instructions
      Instructions
      Up