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

Active substanceImipramineImipramine

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Imipramine

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BIOKOM, CJSC Russia

Melipramine®

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EGIS ZAO Pharmaceutical Plant Hungary

Melipramine®

pills inwards

EGIS ZAO Pharmaceutical Plant Hungary

Melipramine®

solution w / m

EGIS ZAO Pharmaceutical Plant Hungary

Dosage form: & nbsppills

Composition:

1 dragee contains:

active substance: imipramine hydrochloride 25 mg;

Excipients: glycerol 85% (glycerin), titanium dioxide (E 171), macrogol 35000, dye E 172 (iron oxide red), gelatin, magnesium stearate, talc, sucrose and lactose monohydrate.

Description:

Lentil-shaped dragees of brown color with a shiny surface, without or almost no odor.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.A.02 Imipramine

Pharmacodynamics:

Imipramine is a tricyclic antidepressant, a derivative of dibenzoazepine. Imipramine suppresses the synaptic reuptake of norepinephrine and serotonin released by the nerve impulse, and thus facilitates noradrenergic and serotonergic impulse transmission. Imipramine also inhibits muscarinic and H₁-gistaminovye receptors, and therefore has anticholinergic and moderate sedative effects.

Its antidepressant effect develops gradually: the optimal therapeutic effect may occur after 2-4 (possibly, 6-8) weeks of treatment.

Pharmacokinetics:

After oral administration imipramine well absorbed from the gastrointestinal tract. Taking the drug with food does not affect its absorption.

The drug is actively metabolized in the liver with the effect of the first passage: its main metabolite desipramine is formed by demethylation and has pharmacological activity. Levels of imipramine and desipramine in blood plasma have a significant individual variability. After administration of the drug at 50 mg three times a day for 10 days, stationary concentrations of imipramine in blood plasma are 33-85 ng / ml, and the concentration of desipramine is 43-109 ng / ml. Due to reduced metabolism, plasma concentrations of the drug are usually higher in elderly patients than in younger patients. The apparent volume of distribution of imipramine is 10-20 l / kg.

Both active substances largely bind to blood plasma proteins (imipramine 60-96%; desipramine 73-92%).

Imprimin is excreted in the urine (about 80%) and feces (about 20%), mainly in the form of inactive metabolites. With urine and feces, 5-6% of the administered dose of imipramine is released in unchanged form and as an active metabolite of desipramine.After a single administration, the half-life of imipramine is approximately 19 hours (9 to 28 hours) and can be significantly increased in elderly patients and in case of an overdose.

Imipramine penetrates the placental barrier and is excreted into breast milk.

Indications:

Depression and depressive states of various etiologies (endogenous, organic, psychogenic), accompanied by motor and ideator inhibition.

Panic disorder.

Obsessive-compulsive disorder

Enuresis in children over the age of 6 years (in cases where organic disorders are not found).

Contraindications:

Hypersensitivity to any component of the drug or other tricyclic antidepressants from the dibenzoazepine group.

Joint use with MAO inhibitors (see section "Interactions").

Severe impairment of kidney and / or liver function.

Myocardial infarction (acute and subacute periods); severe violations of intracardiac conduction (blockade of the legs of the bundle of His, AV blockade of II st).

Acute intoxication with ethanol, hypnotics, narcotic analgesics and other drugs that depress the central nervous system.

Closed-angle glaucoma.

Children under 6 years.

Pregnancy and lactation.

Carefully:

Chronic alcoholism, bronchial asthma, bipolar disorders (manic-depressive psychosis), oppression of bone marrow hematopoiesis, SSS diseases (angina pectoris, arrhythmia, heart block, CHF, myocardial infarction), pheochromocytoma and neuroblastoma (risk of hypertensive crisis), stroke, motor function impairment Gastrointestinal tract (risk of paralytic obstruction), hepatic and / or renal insufficiency, thyrotoxicosis, prostatic hyperplasia (accompanied by urinary retention), schizophrenia (possible an active tion of psychosis), epilepsy, old age.

Dosing and Administration:

The daily dose and method of application should be set individually according to the nature and severity of the symptoms.

The necessary therapeutic effect can be achieved in 2-4 weeks (possibly, in 6-8 weeks) after the initiation of therapy. Treatment should begin with low doses, which should be gradually increased to achieve the lowest effective and maintenance dose. Increasing the dose to achieve an effective level requires extreme caution in elderly patients and persons under the age of 18 years.

Depression

Out-patient patients aged 18 to 60 years:

The usual initial dose is 1-3 times 25 mg, followed by a gradual increase to 150-200 mg per day by the end of the first week of treatment. The usual maintenance dose is 50 to 100 mg per day.

Stationary patients aged 18 to 60 years:

In a hospital environment - in severe cases - the initial dose is 75 mg per day, followed by increasing to 25 mg daily to 200 mg daily (exceptionally - up to 300 mg per day).

Patients older than 60 years or younger than 18 years:

Treatment should be started with the lowest possible dose. The initial dose can be gradually increased to 50-75 mg per day. It is recommended to find the optimal dose within 10 days and maintain this dose until the end of the course of treatment.

Panic disorders

Treatment should be started with the lowest possible dose. The transient increase in anxiety at the beginning of therapy can be prevented or eliminated by benzodiazepines, which can then be gradually eliminated as anxiety symptoms are eliminated. The dose of Melipramine can be gradually increased to 75-100 mg per day (in exceptional cases, up to 200 mg per day). The minimum duration of treatment is 6 months. At the end of the course of treatment, gradual withdrawal of the preparation of Melipramine is recommended.

Children

The drug should be prescribed to children only older than 6 years and exclusively for short-term adjuvant therapy of nocturnal urinary incontinence, when it is possible to exclude organic lesions.

Recommended doses:

- at the age of 6 to 8 years (body weight 20 - 25 kg): 25 mg per day;

- at the age of 9 to 12 years (body weight 20 - 35 kg): 25-50 mg per day;

- over the age of 12 years (body weight 35 kg): 50-75 mg per day.

Doses higher than those recommended are justified only in the absence of a satisfactory response after one week of taking the lowest doses.

In children, the daily dose should never exceed 2.5 mg / kg body weight.

It is recommended to use the lowest dose from the above range of doses. The daily dose should be given at one time after dinner or at bedtime. If urinary incontinence occurs at the beginning of a night's sleep, it is recommended to divide the daily dose into two doses (the first portion should be given after noon, and the second one before bedtime).

The duration of treatment should be at least 3 months. The maintenance dose can be reduced depending on changes in the clinical picture. At the end of the course of treatment, Melipramine® should be discontinued gradually.

Side effects:

Some of the side effects listed below depend on the dose and disappear when the dose decreases or when continuing treatment.Some side effects are difficult to distinguish from symptoms of depression (eg, fatigue, sleep disorders, agitation, anxiety, dry mouth).

The intake of imipramine should be discontinued if severe neurological or psychiatric reactions occur.

Elderly patients are more sensitive to anticholinergic, neurological, psychiatric and cardiovascular effects. In such patients, the ability to metabolize and excrete medicinal substances may be reduced, which leads to a risk of increasing their concentration in the blood plasma.

The frequency of adverse events was assessed as follows: ≥ 10% of frequent, infrequent ≥1 and <10%, rare ≥0,001-1%, very rare <0.001%

From the central nervous system:

Infrequent: fatigue, yawning, drowsiness, restlessness, increased anxiety, agitation, sleep disturbances, "nightmarish" dream, swings from depressed to hypomanic or manic state, delirium, confusion (especially in elderly patients and those suffering from Parkinson's disease), disorientation and hallucinations, decreased ability to concentrate.

Frequent: tremor.

Infrequent: paresthesia, headache, dizziness.

Rare: epileptic seizures, activation of psychotic symptoms, depersonalization. Very rare: aggressiveness, EEG changes, myoclonia, weakness, extrapyramidal symptoms, ataxia, speech disorders, hyperpyrexia.

From the cardiovascular system:

Frequent: sinus tachycardia and clinically insignificant changes in ECG (T wave and interval ST) in patients with a healthy heart, orthostatic hypotension.

Infrequent: arrhythmias, conduction disorders (broadening of the complex QRS, lengthening the interval PR, bundle branch blockade), palpitations.

Very rare: increase of arterial pressure, decompensation of cardiac activity, spasm of peripheral blood vessels.

From the gastrointestinal tract:

Infrequent: nausea, vomiting, refusal of food.

Very rare: stomatitis, defeat of the tongue, gastrointestinal disorders.

Anticholinergic effects:

Frequent: dry mouth, sweating, constipation, impaired vision, visual acuity, hot flushes. Infrequent: violation of urination.

Very rare: mydriasis, glaucoma, paralytic intestinal obstruction.

Hepatic Effects:

Infrequent: increased transaminases.

Very rare: hepatitis with or without jaundice.

From the skin:

Infrequent: skin allergic reactions (rash, hives).

Very rare: edema (local or generalized), photosensitization, petechiae, hair loss.

Endocrine system and metabolism:

Frequent: increase in body weight.

Infrequent: violation of libido and potency.

Very rare: breast enlargement, galactorrhea, syndrome of impaired secretion of antidiuretic hormone, increase or decrease of blood sugar level, decrease in body weight, increase in size (edema) of testicles.

Hypersensitivity:

Very rare: allergic alveolitis (pneumonitis) with eosinophilia or without it, systemic anaphylactic reactions, including hypotension.

On the part of the hematopoiesis system:

Very rare: eosinophilia, leukopenia, agranulocytosis, thrombocytopenia and purpura.

Other:

Noises in the ears, hypoproteinemia.

Overdose:

Symptoms: system dizziness, drowsiness, insomnia, hallucinations, confusion, stupor, coma,ataxia, restlessness, agitation, hyperreflexia, rigidity of muscles, athetoid and choreiform movements, convulsions, hypotension, tachycardia, arrhythmia, impaired excitation, heart failure; in very rare cases - heart failure, respiratory depression, cyanosis, shock, vomiting, fever, sweating, mydriasis, oliguria or anuria.

Treatment: If you suspect an overdose of imipramine, the patient should be hospitalized and kept under close supervision for a period of at least 72 hours. There is no specific antidote, therefore symptomatic and supportive therapy is indicated. Since the anticholinergic effect of the drug may delay the evacuation of the stomach contents of the patient (by 12 or more hours), it is necessary to rinse the stomach as soon as possible or induce vomiting, if the patient is conscious, and also to enter Activated carbon.

Continuous monitoring of the cardiovascular system, gases and electrolytes of blood is required. Symptomatic treatment, it is possible to prescribe anticonvulsant therapy (for example, diazepam, phenytoin, phenobarbital, inhalation anesthetic + muscle relaxant), artificial respiration, establish a temporary pacemaker, introduce plasma substitutes, dopamine or dobutamine; in exceptional cases, there may be a need for resuscitation.

Hemodialysis and peritoneal dialysis are not effective because of a low concentration of imipramine in the blood plasma.

Since the introduction of physostigmine causes pronounced bradycardia, asystole and epileptic seizures, it is not recommended to be used as a treatment for imipramine overdose.

Interaction:

MAO inhibitors: Combination with MAO inhibitors should be avoided, since the action of these two classes of drugs is synergistic and their peripheral noradrenergic effects can increase to toxic levels (hypertensive crisis, hyperpyrexia, myoclonia, agitation, convulsions, delirium, coma). The use of imipramine should not be started earlier than 3 weeks after the abolition of MAO inhibitors (with the exception of the reversible MAO inhibitor moclobemide, after which it is sufficient to wait 24 hours). The three-week interval between the preparations should also be observed when transferring the patient from imipramine to the MAO inhibitor. The introduction of a new drug - an MAO inhibitor or a preparation of Melipramin ® - should start with low doses,which can then be gradually increased with careful monitoring of clinical effects.

Inhibitors of hepatic enzymes: inhibitors of cytochrome isoenzyme P-450 2D6 when combined with imipramine can reduce metabolism, which can increase the levels of imipramine in the blood plasma. The inhibitors of this type also include substances that are not a substrate CYP2D6 (cimetidine or methylphenidate), but also metabolized by this enzyme, for example, many other antidepressants, phenothiazines, antiarrhythmic drugs of type 1c (propafenone, flecainide). All antidepressants of the class of selective serotonin reuptake inhibitors are, to varying degrees, inhibitors CYP2D6. Therefore, care should be taken when combining imipramine with these drugs, as well as when transferring the patient from an antidepressant class of selective serotonin reuptake inhibitors to imipramine (and vice versa); especially in the case of fluoxetine because of its long half-life. Tricyclic antidepressants can increase levels of antipsychotic drugs in blood plasma because of competition at the level of hepatic enzymes.

Oral contraceptives and estrogens: in some cases, women who use oral contraceptives or preparations of estrogen hormones simultaneously with tricyclic antidepressants experienced a decrease in antidepressant effect and the development of toxic effects of antidepressants. Therefore, caution is needed when combining these drugs and the dose of one or another drug should be reduced when toxic effects appear.

Inductors of hepatic enzymes: (alcohol, nicotine, meprobamate, barbiturates, antiepileptics, etc.) increase the metabolism of imipramine, reduce its level in plasma and weaken the antidepressant effect.

Anticholinergic drugs (for example, phenothiazines, antiparkinsonics, antihistamines, atropine, biperidin) increase anticholinergic and side effects (eg, paralytic intestinal obstruction) when combined with imipramine. The combination with these drugs requires careful monitoring of patients and careful selection of a dose.

Medications that depress the central nervous system: a combination of imipramine with agents depressing the central nervous system (eg, opiates, benzodiazepines,barbiturates and general anesthetics) and alcohol significantly increases the main and side effects of these drugs. Antipsychotic drugs can increase the levels of tricyclic antidepressants in blood plasma and enhance their main and side effects. A dose reduction may be required. Co-administration with thioridazine can cause severe arrhythmia.

Preparations of thyroid hormones can enhance the antidepressant effect of imipramine and its side effect on the heart. Therefore, their joint application requires special care.

Adrenergic neuron blockers: imipramine can reduce the antihypertensive effects of the joint adrenergic neuron blockers (guanethidine, betanidine, reserpine, clonidine and alpha-methyldopa). Therefore, patients who require concomitant antihypertensive therapy should be assigned other types of antihypertensive agents (eg, diuretics, vasodilators or beta-blockers).

Sympathomimetics: imipramine enhances the cardiovascular effects of sympathomimetics (mainly adrenaline, norepinephrine, isoprenaline, ephedrine, phenylephrine).

Phenytoin: imipramine reduces the anticonvulsant effect of phenytoin.

Quinidine: in order to avoid conduction disorders and arrhythmias, tricyclic antidepressants should not be used in combination with antiarrhythmic drugs such as quinidine.

Oral anticoagulants: tricyclic antidepressants inhibit the metabolism of oral anticoagulants and prolong their half-life. This increases the risk of bleeding, which is why careful metabolic control and monitoring of plasma prothrombin levels is recommended.

Antidiabetics: blood sugar levels may change during the course of treatment with imipramine. Therefore, it is recommended to control the blood sugar level at the beginning and end of the course of treatment, as well as when changing the dose.

Joint application with alpha-adrenostimulyatorami for intranasal administration or for use in ophthalmology (with significant systemic absorption), the vasoconstrictive effect of the latter may be enhanced.

M-holinoblokatory and antipsychotic drugs (neuroleptics) increase the risk of hyperpyrexia (especially in hot weather).

When co-appointed with other hematotoxic drugs possibly increased hematotoxicity.

Special instructions:

The therapeutic effect can occur no sooner than 2-4 weeks after the start of treatment. As with the use of other antidepressants, the later onset of a therapeutic effect means that the patient's suicidal tendencies are not immediately eliminated, and the patient needs careful medical attention before significantly improving his condition. In connection with the risk of suicidal actions at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptics may be indicated. The minimum duration of taking a maintenance dose is 6 months.

Imipramine should be discontinued gradually, as a sudden discontinuation of its administration may cause withdrawal symptoms (nausea, headache, general malaise, anxiety, anxiety, sleep disorders, cardiac rhythm disturbances, extrapyramidal symptoms), especially in children. In patients with bipolar depression imipramine can provoke a manic or hypomanic state. The drug should not be taken during manic episodes.

Like other tricyclic antidepressants, imipramine reduces the threshold of convulsive readiness.Therefore, patients with epilepsy, as well as having anamnesis manifestations of spasmophilia and epilepsy, need careful medical supervision and sufficient anticonvulsant therapy (see also: Interaction with other drugs: phenytoin and inducers of enzymes).

Receiving impramina increases the risk of electroconvulsive therapy, and therefore it is contraindicated during electroconvulsive therapy.

As a paradoxical reaction, anxiety may worsen in patients with panic disorders during the first days of taking tricyclic antidepressants. The anxiety intensification usually passes independently for 1-2 weeks, however this manifestation can be eliminated if necessary by administration of the benzodiazepine derivative (see the section "Administration and dosage").

In patients with psychoses in the initial period of treatment with tricyclic antidepressants, anxiety, anxiety and agitation may increase.

Due to the presence of an anticholinergic effect, the use of imipramine requires careful medical observation in patients with glaucoma, prostatic hypertrophy and severe constipation, since this drug can intensify the symptoms.

In patients using contact lenses, a decrease in the production of tears and the accumulation of rejected mucus can damage the epithelium of the cornea.

With ischemic heart disease, impaired liver and kidney function, as well as diabetes mellitus (changes in blood sugar levels) imipramine should be used with caution.

Treatment of patients with adrenal gland tumors (pheochromocytoma or neuroblastoma) requires extreme caution. imipramine can provoke hypertensive crisis.

Treating patients with hyperthyroidism or using thyroid medications requires careful medical supervision because of the increased risk of side effects on the heart in these patients.

Because of the possible increase in the risk of arrhythmia and hypotension in general anesthesia, it is necessary before the surgery to notify the anesthesiologist that the patient is taking imipramine.

In the treatment with imipramine, isolated cases of eosinophilia, leukopenia, agranulocytosis, thrombocytopenia, and purpura are described. Therefore, the cellular composition of the blood should be monitored regularly.

With prolonged use of imipramine, there is an increase in the incidence of caries. Therefore, regular consultations of the dentist are necessary.

Side effects can be more pronounced in elderly and younger patients. Therefore, especially at the beginning of the course of treatment, they should be given lower doses (see section "Method of administration and dosage").

Each tablet, coated with a shell, contains 116 mg of lactose. This drug is not recommended for patients with rare hereditary disorders of tolerance to galactose, a hereditary deficiency of lactose Sami or a syndrome of non-absorption of glucose-galactose.

Dragee contains sucrose, therefore it is not recommended to give the drug to patients with rare hereditary phenomena of intolerance to fructose, impaired absorption of glucose-galactose, as well as insufficiency of sugarase / isomaltase.

Imipramine causes photosensitivity, therefore during the course of treatment, intensive sunlight exposure should be avoided.

In predisposed and / or elderly patients imipramine can cause an anticholinergic (delirious) psychotic syndrome, which occurs within a few days after discontinuation of the drug.

Children compared with adults are more sensitive to acute overdose, which should be considered dangerous and potentially lethal for them.

It is forbidden to drink alcoholic beverages during the course of treatment with imipramine.

The following indicators are recommended to monitor before treatment with imipramine and regularly throughout the course of treatment:

- ablood pressure (especially in patients with labile circulation or hypotension);

- fliver function (especially in the presence of liver disease);

- counting of blood cell elements (immediately in case of fever or laryngitis, which may be signs of leukopenia and agranulocytosis, as well as at the beginning of the course of treatment and regularly on its course);

- ECG (in elderly patients and in cardiovascular diseases).

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

At the beginning of treatment should be abandoned driving vehicles and from employment by potentially dangerous activities that require increased concentration and speed of psychomotor reactions. In the future, the degree of restriction is determined for each patient individually.

Form release / dosage:Dragee, 25 mg.

Packaging:

50 drops in a bottle of brown glass.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature of 15-25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014539 / 02

Date of registration:09.02.2009 / 12.01.2015

Expiration Date:Unlimited

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp27.04.2018

Illustrated instructions

Instructions

Melipramine® (Melipramin®)