Melipramine: instructions for use, reviews on forums and for enuresis, price and analogues

Compound

The active ingredient of the drug is imipramine hydrochloride .
Melipramine dragees have the following additional components: titanium dioxide, glycerol 85%, macrogol 35,000, gelatin, talc, lactose monohydrate, red iron oxide, magnesium stearate, sucrose.

Auxiliary components of the solution for intramuscular administration: sodium pyrosulfite, ascorbic acid, sodium chloride , anhydrous sodium sulfite, water for injection.

Additional elements of film-coated tablets: lactose monohydrate, crospovidone, magnesium stearate, povidone K-25. Shell components: hypromellose, dye mixture, magnesium stearate, dimethicone E1049 39%.

Pharmacodynamics and pharmacokinetics

Melipramine is a tricyclic antidepressant. It indiscriminately blocks the reuptake of neurotransmitter monoamines , causing them to accumulate in the synaptic cleft . This leads to increased physiological activity.

The drug also has a thymoleptic effect. It is characterized by concomitant stimulating activity, increases the tone of the body, and provokes a decrease in motor retardation. The medicine has peripheral and central m-anticholinergic , weak antihistamine , myotropic activity .

When taken orally, the drug is characterized by a good degree of absorption from the gastrointestinal tract. Bioavailability can range from 29% to 77%. The maximum plasma concentration is approximately 1-2 hours after ingestion and after half an hour or an hour with intramuscular injections .

The degree of binding to plasma proteins is approximately 85%. The active substance is well distributed in tissues and is able to penetrate the BBB . It also selectively accumulates in the brain, liver and kidneys.

When ingested, it is intensively biotransformed in the liver. Approximately 40% of imipramine hydrochloride is excreted during the day along with urine in the form of metabolites , and 1-2% unchanged. About 20% of the dosage is excreted in bile. The half-life can range from 4 to 24 hours.

Indications for use

Indications for use of the medicine are as follows:

nocturnal enuresis in children;
depression and depressive states of various origins, which are accompanied by motor and ideational retardation ;
obsessive-compulsive disorders;
panic disorders;
behavioral disturbances (increased activity or demand for attention);
chronic pain syndrome;
narcolepsy combined with catalepsy ;
frequent headaches ;
bulimia nervosa;
withdrawal syndrome ;
migraine prevention ;
urinary incontinence.

Contraindications

The drug should not be used for benign prostatic hyperplasia , acute liver and kidney diseases, infectious diseases, diabetes mellitus and heart defects in the stage of decompensation , heart rhythm and conduction , increased convulsive readiness , atony of the bladder , pregnancy (first trimester), breastfeeding , hypersensitivity to tricyclic antidepressants , diseases of the hematopoietic organs, active form of tuberculosis , hyperthyroidism , acute phase of myocardial infarction , severe cardiovascular failure , angle-closure glaucoma , age under 6 years.

This medicine should be used with caution in case of epilepsy .

Contraindications to the use of the drug Melipramine

Melipramine tablets should not be used:

during pregnancy and lactation;
if you are allergic to imipramine or other ingredients of the drug;
allergies to other tricyclic antidepressants of the dibenzoazepine series;
when treated with MAO inhibitors;
if you have a history of heart attacks (myocardial infarction) or heart rhythm disturbances (arrhythmias);
severe kidney and/or liver disease;
with urinary retention (prostatic hypertrophy);
presence of narrow-angle glaucoma.

Melipramine injection solution should not be administered to children under 6 years of age.

Side effects

Adverse reactions when using the drug Melipramine may be as follows:

CVS: tachycardia , orthostatic hypotension , arrhythmia , conduction disturbances ;
CNS: agitation , headache , paresthesia , convulsions, coordination disorders, hallucinations , phase inversion in the case of bipolar psychosis , dizziness , insomnia , tremor , dysarthria , confusion accommodation disturbances ;
hematopoietic system: leukocytosis , eosinophilia ;
allergy : exanthema ;
Gastrointestinal tract: constipation ;
urinary and reproductive systems: urinary retention, decreased libido ;
endocrine system: gynecomastia , galactorrhea ;
other: dry mouth, photosensitivity, fever , hair loss, increased sweating .

hepatitis , leukopenia , and agranulocytosis develop .

Side effects of the drug Melipramine

The most common side effects of the drug are drowsiness, postural hypotension, tachycardia and atropine-like symptoms: dry mouth, constipation, urinary retention, blurred vision, impaired accommodation, increased body temperature and intraocular pressure. Other less common side effects are neurological:

headache, peripheral neuropathy, tinnitus, extrapyramidal symptoms (tremor, ataxia, difficulty speaking, especially in the elderly), confusion, delirium;
epileptogenic effect: primarily in patients with epilepsy or with a tendency to seizures;
cardiovascular: rarely, mainly after administration of the drug in high doses to especially sensitive patients - arrhythmia, severe hypotension and/or vasospasm, which is manifested by blue discoloration of the fingers;
gastrointestinal: very rarely - hepatitis with impaired liver function, icterus of the skin and sclera, pain in the liver, metallic taste in the mouth, inflammation of the oral mucosa (stomatitis), nausea, vomiting and in exceptional cases - paralytic ileus;
allergic skin reactions (14–60 days from the start of treatment): urticaria, angioedema, photosensitivity;
endocrine: breast enlargement, galactorrhea, complications of diabetes mellitus, decreased glucose tolerance, very rarely - decreased production of antidiuretic hormone;
sexual disorders - decreased libido, impotence, painful ejaculation, impaired orgasm;
very rarely, mainly in elderly people, changes in peripheral blood parameters during laboratory tests.

Instructions for use of Melipramine (Method and dosage)

When administering the drug intramuscularly , start with 25 mg 3 times a day. If necessary, the dosage can be gradually increased over the following days. But the daily dose should not be more than 100 mg. After a week of using the medication intramuscularly, the dose is gradually reduced by replacing one injection with a pill or tablet. From the 13th day of therapy, they completely switch to oral administration at a dosage of 25 mg 4 times every day. If symptoms return, you can start taking intramuscular injections .

Instructions for use of Melipramine for the elderly recommend starting therapy with small doses. Usually this is 10 mg/day. Then the amount of the drug is gradually increased to 50 mg. The maximum dosage for older people is 100 mg.

Dragees and tablets are taken orally immediately after meals. Dosages are calculated individually. Typically, for adult patients, the course begins with a dose of 25-50 mg every day 3-4 times. The instructions for use of Melipramine indicate that the daily dosage can be gradually increased by 25 mg and brought to 250-300 mg. The highest doses of the drug for adult patients are as follows:

single dose – 100 mg;
daily - 300 mg in hospital or 200 mg on an outpatient basis .

The duration of therapy for mild forms of depression is an average of 5 weeks.

For maintenance therapy, a single dose of medication is recommended in the evening.

For children, the drug is given as an antidepressant at the beginning of the course at a dosage of 10 mg. During 10 days of treatment, it can be gradually increased. For children, the following maximum dosages are indicated:

age 6-8 years - give 20 mg;
age 8-14 years - give 25 mg;
age over 14 years - give 100 mg (in 2 doses).

In case of bedwetting , at the beginning of therapy, take the medicine in the following dosages:

children 6-8 years old – 25 mg;
children 9-12 years old – 25-50 mg;
children over 12 years old – 50-75 mg.

This should be done once a day an hour before bedtime. If urinary incontinence occurs in the early hours of sleep, the dosage can be divided into 2 doses. In this case, the first half is taken in the middle of the day, and the second just before bedtime. If the desired effect is not achieved within a week, the dosage can be increased. The maximum daily dose for children is 2.5 mg/kg.

In case of severe depression in a hospital , the medicine can be used simultaneously intramuscularly and orally . If the drug is taken as an antidepressant , administer up to 100 mg per day in several doses. The highest single dose for adult patients is 50 mg, daily dose is 300 mg.

If you stop taking it too soon, it may cause depression . The medication must be discontinued gradually.

Melipramine 25 mg 50 pcs. film-coated tablets

pharmachologic effect

Imipramine, a dibenzoazepine derivative, is a tricyclic antidepressant.
Imipramine inhibits the synaptic reuptake of norepinephrine and serotonin released upon neuron stimulation, thereby facilitating noradrenergic and serotonergic impulse transmission. Imipramine also blocks m-cholinergic and H1-histamine receptors, thus providing m-anticholinergic and moderate sedative effects. The effects of the antidepressant develop gradually: the optimal therapeutic effect is achieved after 2-4 (possibly 6-8) weeks of treatment.

Composition and release form Melipramin 25 mg 50 pcs. film-coated tablets

Tablets - 1 tablet:

Active substance: imipramine hydrochloride 25 mg.
Excipients: magnesium stearate - 1.5 mg, crospovidone - 3 mg, talc - 3 mg, povidone (K-25) - 7 mg, lactose monohydrate - 110.5 mg.
Shell composition: hypromellose - 2.61 mg, magnesium stearate - 0.24 mg, red iron oxide dye (CI77491, E172) - 0.68 mg, black iron oxide dye (CI77499, E172) - 0.12 mg, dimethicone (E1049 39%) - 0.35 mg.

50 pcs. - dark glass bottles with tamper evident and accordion shock absorber (1) - cardboard packs.

Description of the dosage form

Tablets, film-coated, red-brown, round, biconvex, with a matte surface, odorless or almost odorless.

Characteristic

Tricyclic antidepressant with a predominantly stimulating effect, a derivative of dibenzazepine.

Directions for use and doses

The dose and frequency of administration are determined individually depending on the nature and severity of symptoms. As with other antidepressants, it takes at least 2-4 weeks (possibly 6-8 weeks) to achieve a therapeutic effect. Treatment should begin with low doses and gradually increase them to select the lowest effective maintenance dose. Dose titration until effectiveness is achieved requires special caution in the elderly and in patients under 18 years of age.

Depression

Outpatients 18-60 years old:

The standard dose is 25 mg 1-3 times / day, the dose can be gradually increased to a daily dose of 150-200 mg by the end of the first week of therapy. The standard maintenance dose is 50-100 mg/day.

Hospital patients aged 18-60 years:

In a hospital setting, in especially severe cases, the initial dose is 75 mg/day, the dose can be increased by 25 mg/day to a daily dose of 200 mg (in exceptional cases, the daily dose can reach 300 mg).

Patients over 60 years of age:

In these age groups, a pronounced response to the above doses may be observed, therefore, treatment should begin with the lowest possible doses. The initial dose may be gradually increased to a total daily dose of 50-75 mg. It is recommended to achieve the optimal dose within 10 days and maintain this dose throughout the entire treatment period.

Panic disorders

Since this group of patients has an increased incidence of side effects of the drug, treatment should begin with the lowest possible dose. Transient increases in anxiety at the start of antidepressant treatment can be prevented or managed with benzodiazepines, the dose of which is gradually reduced as anxiety symptoms improve. The dose of Melipramine can be gradually increased to 75-100 mg/day (in exceptional cases up to 200 mg). The minimum duration of treatment is 6 months. Upon completion of treatment, it is recommended to discontinue Melipramine gradually.

Children:

The drug should be prescribed only to children over 6 years of age exclusively as temporary adjuvant therapy for nocturnal enuresis, with the exception of organic pathology.

Recommended doses are:

6-8 years (with body weight 20-25 kg): 25 mg/day.

9-12 years (with body weight 25-35 kg): 25-50 mg/day.

Over 12 years of age and body weight above 35 kg: 50-75 mg/day.

Exceeding recommended doses is justified only in cases where there is no satisfactory response to therapy after 1 week of treatment with the drug at lower doses.

The daily dose in children should not exceed 2.5 mg/kg body weight.

It is recommended to use the lowest dose in the above dosage range. The daily dose is recommended to be taken once after a meal before bedtime. If nocturnal enuresis occurs in the early evening hours, it is recommended to divide the daily dose into two doses: one during the day and one at night. The duration of treatment should not exceed 3 months. Depending on changes in the clinical picture of the disease, the maintenance dose may be reduced. Upon completion of therapy, Melipramine should be discontinued gradually.

Pharmacodynamics

Reduces motor retardation, improves mood, helps normalize sleep, and has a pronounced psychostimulating effect. At the beginning of treatment, sedation may predominate. The antidepressant effect develops gradually, the optimal therapeutic effect is achieved 1-3 weeks (possibly 4 weeks) after the start of treatment.

Pharmacokinetics

When taken orally, imipramine is well absorbed from the gastrointestinal tract. Sharing food does not affect the absorption of imipramine.

The compound undergoes extensive first-pass metabolism in the liver: its main pharmacologically active metabolite, desipramine (demethyl-imipramine), is formed by demethylation. Plasma concentrations of imipramine and desipramine are characterized by high individual variability. After 10 days of taking imipramine at a dose of 50 mg 3 times a day, plasma concentrations of imipramine at steady state range from 33 to 85 ng/ml, concentrations of desipramine range from 43 to 109 ng/ml. Due to decreased metabolism, plasma concentrations are usually higher in older patients compared to younger patients.

The apparent Vd of imipramine is 10-20 l/kg.

Both active compounds are significantly bound to plasma proteins (imipramine 60-96%, desipramine 73-92%).

Imipramine is excreted by the kidneys (about 80%) and feces (about 20%), mainly in the form of inactive metabolites. Excretion in urine and feces of unchanged imipramine and its active metabolite desipramine is up to 5-6% of the dose taken. After taking one dose, T1/2 of imipramine is about 19 hours and can vary from 9 to 28 hours, significantly increasing in the elderly and in case of overdose.

Imipramine crosses the placental barrier and is excreted in breast milk.

Indications for use Melipramin 25 mg 50 pcs. film-coated tablets

All forms of depression (with and without anxiety): major depression, depressive phase of bipolar disorder, atypical depression, depressive states;
panic disorders;
bedwetting in children (over the age of 6 years; for short-term adjuvant therapy if an organic cause can be excluded).

Contraindications

Hypersensitivity to any component of the drug or other tricyclic antidepressants from the dibenzoazepine group;
use of MAO inhibitors;
recent myocardial infarction;
violation of intracardiac conduction;
heart rhythm disturbance;
manic episodes;
severe impairment of kidney and/or liver function;
urinary retention;
angle-closure glaucoma;
age up to 6 years when treating bedwetting and up to 18 years when treating depression and panic disorder (lack of sufficient clinical experience);
pregnancy and breastfeeding;
galactose intolerance, congenital lactase deficiency or glucose and galactose maladsorption syndrome (tablets contain lactose monohydrate).

Application of Melipramine 25 mg 50 pcs. film-coated tablets during pregnancy and breastfeeding

Since in certain cases the possibility of a relationship between the use of tricyclic antidepressants and fetal development disorders has been established, the use of the drug during pregnancy is contraindicated.

Imipramine is excreted in breast milk; therefore, use of the drug during lactation is contraindicated.

Use in children

The drug is contraindicated in children under 6 years of age when treating bedwetting and under 18 years of age in treating depression and panic disorder (lack of sufficient clinical experience).

The drug should be prescribed only to children over 6 years of age exclusively as temporary adjuvant therapy for nocturnal enuresis, with the exception of organic pathology.

Recommended doses are:

6-8 years (with body weight 20-25 kg): 25 mg/day.

9-12 years (with body weight 25-35 kg): 25-50 mg/day.

Over 12 years of age and body weight above 35 kg: 50-75 mg/day.

Exceeding recommended doses is justified only in cases where there is no satisfactory response to therapy after 1 week of treatment with the drug at lower doses.

The daily dose in children should not exceed 2.5 mg/kg body weight.

special instructions

Suicide/suicidal ideation or clinical worsening

Depression is associated with an increased risk of suicidal ideation, self-harm and suicide (suicidal events). This risk persists until significant remission occurs. Since improvement may not occur within the first few weeks of treatment or more, careful monitoring of the patient is required until such improvement is achieved. In general clinical experience, the risk of suicide may be increased in the early stages of recovery. Suicide rates increase in children and young people under 24 years of age.

Other psychiatric conditions for which Melipramine is prescribed may also be associated with an increased risk of suicidal events. In addition, these conditions may accompany major depressive disorder. Therefore, when treating patients with other mental disorders, the same precautions are required as when treating patients with major depressive disorder.

Patients with a history of suicidal behavior or patients with significant suicidal ideation before starting therapy are at increased risk of suicidal ideation or suicide attempts and therefore require careful monitoring during therapy. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders found an increased risk of suicidal behavior with antidepressants compared with placebo.

Drug therapy should be accompanied by careful monitoring of patients, in particular high-risk patients, especially in the early stages of treatment and after dose changes. Patients (and their caregivers) should be warned to monitor for any clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior and to seek immediate medical attention if these symptoms occur.

The therapeutic effect can be expected no earlier than 2-4 weeks of treatment. As with other antidepressants, the delayed onset of therapeutic effect means that the patient's suicidal tendencies will not be eliminated immediately, so the patient needs careful medical monitoring until significant improvements are achieved.

Therapy with a maintenance dose of the drug should continue for at least 6 months.

Imipramine therapy should be discontinued gradually, since abrupt cessation of the drug may cause withdrawal symptoms (nausea, headache, fatigue, restlessness, anxiety, sleep disorders, arrhythmia, extrapyramidal symptoms).

In the case of bipolar depression, imipramine may contribute to the development of mania. The drug should not be used during manic episodes.

Like other tricyclic antidepressants, imipramine lowers the seizure threshold, so patients with epilepsy and spasmophilia or a history of epilepsy require careful medical monitoring and adequate anticonvulsant therapy.

Serotonin syndrome can occur when using drugs that inhibit the reuptake of serotonin (tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, etc.) or block the metabolism of serotonin (MAO inhibitors). Serotonin syndrome can develop when they are combined or when combined with other drugs that enhance the effect of serotonin (L-tryptophan, pentazocine, meperidine, bromocriptine, dextromethorphan, etc.). Due to the risk of developing serotonin syndrome, caution is required when combining imipramine with such drugs, as well as when transferring a patient from antidepressants that are selective serotonin reuptake inhibitors to imipramine (or vice versa), especially in the case of fluoxetine (given the long half-life of this drug). drug). Serotonin syndrome, which includes three groups of symptoms - motor, autonomic and mental disorders - develops within a few hours or days after starting treatment with a serotonin mimetic drug or increasing its dose. Treatment includes discontinuation of seroonergic agents and symptomatic measures.

Melipramine increases the risk associated with electroconvulsive therapy, therefore the use of the drug during electroconvulsive therapy is not recommended.

As a paradoxical reaction, patients with panic disorders may experience increased anxiety in the first few days of therapy. Increased anxiety usually resolves spontaneously within 1-2 weeks; benzodiazepine derivatives can be used to treat it if necessary.

In patients with psychosis, increased restlessness, anxiety and agitation may occur when starting treatment with tricyclic antidepressants.

Due to the m-anticholinergic effect, the use of imipramine requires careful medical supervision in cases of glaucoma, prostatic hyperplasia and severe constipation, since treatment may lead to an increase in the severity of these symptoms. In patients who wear contact lenses, decreased tear production and accumulation of mucous discharge can lead to damage to the corneal epithelium.

Imipramine should be used with caution in patients with ischemic heart disease, impaired liver and kidney function, and diabetes mellitus (changes in blood glucose concentrations).

Treatment of patients with adrenal tumors (pheochromocytoma or neuroblastoma) requires special caution, since imipramine can provoke the development of a hypertensive crisis.

Treatment of patients with hyperthyroidism and patients using thyroid hormone preparations requires careful medical supervision, taking into account the increased risk of cardiovascular adverse reactions in these patients.

Given the increased risk of arrhythmia and decreased blood pressure during general anesthesia, the anesthesiologist should be informed before surgery that the patient is taking imipramine.

In some cases, the development of eosinophilia, leukopenia, agranulocytosis, thrombocytopenia and purpura has been reported during treatment with imipramine, so regular monitoring of blood test parameters is required.

With long-term therapy with antidepressants, there is an increase in the incidence of dental caries, so regular dental examinations are required.

Side effects may be more severe in older and younger patients, so lower doses may be required, especially at the beginning of treatment. Imipramine causes photosensitivity, so during treatment it is necessary to avoid exposure to intense sunlight.

In patients with a predisposition and/or elderly patients, imipramine can cause m-anticholinergic (delirious) syndrome, which resolves within a few days after discontinuation of the drug.

Melipramine film-coated tablets contain lactose monohydrate. During therapy with imipramine, it is prohibited to drink alcoholic beverages.

Before starting treatment and regularly during treatment, it is recommended to monitor the following indicators:

Blood pressure (especially in patients with unstable circulation or arterial hypotension);
liver function (especially in patients with liver disease);
peripheral blood counts (immediately with fever or laryngitis, as they may be a sign of leukopenia and agranulocytosis, in other cases before starting therapy and regularly during therapy);
ECG (in elderly patients and patients with heart disease).

Impact on the ability to drive a car and operate machinery

The use of the drug Melipramine leads to an increased risk of accidents, therefore, at the beginning of therapy, driving a car and working with machinery should be prohibited. Later, the degree and duration of these restrictions are determined by the doctor individually.

Overdose

Symptoms:

CNS: dizziness, lethargy, stupor, coma, ataxia, restlessness, agitation, increased reflexes, muscle rigidity, athetoid and chorea-like movements, convulsions.

Cardiovascular system: decreased blood pressure, tachycardia, arrhythmia, conduction disturbances, shock, heart failure, and in extremely rare cases, cardiac arrest.

Other: respiratory depression, cyanosis, vomiting, fever, sweating, mydriasis, oliguria or anuria.

Overdose symptoms may occur within 4-6 days. Children, compared to adults, are more sensitive to acute overdose, which should be considered dangerous and potentially fatal for them.

Treatment:

Patients with suspected imipramine overdose should be hospitalized and observed in hospital for at least 72 hours. There is no specific antidote; treatment primarily consists of symptomatic and supportive therapy. Since the m-anticholinergic effect of the drug can lead to a delay in gastric emptying (for 12 hours or more), a gastric tube should be inserted as soon as possible or vomiting should be induced (if the patient is conscious) and activated charcoal should be administered. Continuous monitoring of cardiovascular activity, gas and electrolyte composition of the blood is required. As symptomatic treatment, anticonvulsant therapy (IV diazepam, phenobarbital, inhalational anesthetics and muscle relaxants), artificial ventilation, installation of a temporary pacemaker, administration of plasma replacement fluids, dopamine or dobutamine IV by drip may be used; in exceptional cases, cardiopulmonary therapy may be required. pulmonary resuscitation. Hemodialysis or peritoneal dialysis is ineffective given the low plasma concentrations of imipramine. Due to the high Vd, forced diuresis is also ineffective. Given reports that physostigmine can cause severe bradycardia, asystole and epileptic seizures, its use in imipramine overdose is not recommended.

Side effects Melipramine 25 mg 50 pcs. film-coated tablets

The undesirable effects listed below do not necessarily occur in all patients. Some of the side effects are dose dependent and will subside after the dose is reduced or spontaneously as treatment continues. Some side effects may be difficult to distinguish from symptoms of depression (eg, fatigue, sleep disturbance, agitation, anxiety, dry mouth).

Imipramine should be temporarily discontinued if severe neurological or psychiatric reactions occur.

Elderly patients are particularly sensitive to anticholinergic, neurological, psychiatric or cardiovascular effects. The ability to metabolize and eliminate the drug may be reduced, leading to a risk of increased plasma concentrations.

Undesirable effects observed with the use of the drug Melipramine are classified according to body systems and are listed below as very often (≥1/10), often (≥1/100 and

In each frequency group, undesirable effects are listed in order of decreasing severity.

Laboratory tests: often - increased transaminase activity.

From the cardiovascular system: very often - sinus tachycardia and ECG changes that are not clinically significant (changes in the T wave and ST segment) in patients with normal heart function, orthostatic hypotension, hot flashes; often - arrhythmias, conduction disturbances (expansion of the QRS complex and PR interval, His bundle block), palpitations; rarely - cardiac decompensation, increased blood pressure, peripheral vasospastic reactions.

From the hematopoietic system: rarely - agranulocytosis, leukopenia, thrombocytopenia and purpura, eosinophilia.

From the side of the central nervous system: very often - tremor; often - paresthesia, headache, dizziness, delirious confusion (especially in elderly patients with Parkinson's disease), disorientation and hallucinations, transition from depression to hypomania or mania, agitation, restlessness, increased anxiety, fatigue, insomnia, sleep disturbances, disturbances libido and potency; infrequently - convulsions, activation of psychotic symptoms; rarely - extrapyramidal symptoms, ataxia, aggressiveness, myoclonus, speech disorders.

From the organs of vision and hearing: very often - disturbance of accommodation, blurred visual perception; rarely - glaucoma, mydriasis; unknown - ringing in the ears.

From the gastrointestinal tract: very often - constipation, dry mouth; often - vomiting, nausea; rarely - paralytic ileus, stomach upset, stomatitis, tongue damage, hepatitis not accompanied by jaundice.

From the urinary system: often - urinary disorders.

From the skin: very often - increased sweating; often - allergic skin reactions (skin rash, urticaria); rarely - swelling (local or generalized), photosensitivity, itching, petechiae, hair loss.

From the endocrine system: rarely - enlargement of the mammary glands, galactorrhea, syndrome of inadequate secretion of antidiuretic hormone, increase or decrease in the concentration of glucose in the blood plasma.

Metabolic and nutritional disorders: very often - weight gain; often - anorexia; rarely - weight loss.

Other: rarely - hyperpyrexia, weakness, systemic anaphylactic reactions, including decreased blood pressure, allergic alveolitis (pneumonitis) with or without eosinophilia. People over 50 years of age who take antidepressants have an increased incidence of bone fractures.

During therapy with imipramine and in the early stages after discontinuation of the drug, cases of suicidal thoughts and suicidal behavior were observed.

Drug interactions

MAO inhibitors: Combination with MAO inhibitors should be avoided as these two types of drugs have a synergistic effect and their peripheral noradrenergic effects can reach toxic levels (hypertensive crisis, hyperpyrexia, myoclonus, agitation, convulsions, delirium, coma). For safety reasons, imipramine therapy should not be started earlier than 3 weeks after the end of therapy with MAO inhibitors (with the exception of moclobemide, a reversible MAO inhibitor, for which a break of 24 hours is sufficient). A drug-free period of three weeks should also be observed when switching a patient from imipramine to MAO inhibitors. Treatment with MAO inhibitors or imipramine should be started with small doses and gradually increased while carefully monitoring clinical effects.

Inhibitors of liver microsomal enzymes: when used together with imipramine, inhibitors of the cytochrome P450 isoenzyme 2D6 may lead to a decrease in the metabolism of the drug and, thus, lead to an increase in the concentration of imipramine in the blood plasma. Inhibitors of this type include drugs that are not substrates of the cytochrome P450 2D6 isoenzyme (cimetidine, methylphenidate), as well as drugs that are metabolized by this isoenzyme (i.e., many other antidepressants, phenothiazines, class I antiarrhythmic drugs (propafenone, flecainide)). All antidepressants classified as selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 isoenzyme 2D6 of varying potency. Accordingly, caution is required when combining imipramine with these drugs, as well as when transferring a patient from antidepressants that are selective serotonin reuptake inhibitors to imipramine (and vice versa), especially in the case of fluoxetine (given the long half-life of this drug). Tricyclic antidepressants can lead to increased plasma concentrations of antipsychotic drugs (competition at the level of liver enzymes).

Oral contraceptives, estrogens: a decrease in the effectiveness of antidepressants and the development of toxic effects of antidepressants is sporadically observed in women taking oral contraceptives or estrogen preparations and tricyclic antidepressants together. Therefore, the combined use of these drugs requires caution, and if toxic effects develop, the dose of one of the drugs should be reduced.

Inducers of microsomal liver enzymes (alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs, etc.) increase the metabolism of imipramine and reduce its concentration in the blood plasma and antidepressant effects.

Drugs with m-anticholinergic properties (for example, phenothiazines, drugs for the treatment of parkinsonism, H1-histamine receptor blockers, atropine, biperedine) when used together with imipramine are characterized by an increase in antimuscarinic effects and side effects (for example, paralytic ileus). Combination therapy with these drugs requires careful monitoring of the patient and careful selection of doses.

CNS depressants: The combination of imipramine with drugs that cause CNS depression (for example, narcotic analgesics, benzodiazepines, barbiturates, drugs for general anesthesia) and alcohol leads to a marked increase in the effects and side effects of these drugs.

Antipsychotic drugs may increase plasma concentrations of tricyclic antidepressants, thereby increasing side effects. A dose reduction may be required. Concomitant use with thioridazine may cause severe arrhythmia.

Thyroid hormone preparations may increase the antidepressant effect of imipramine, as well as its side effects on the heart, so their combined use requires special caution.

Sympatholytics: Imipramine may lead to a decrease in the antihypertensive effect of concomitantly used adrenergic neuron blockers (guanethidine, betanidine, reserpine, clonidine, methyldopa). Therefore, in patients requiring concomitant use of drugs to treat hypertension, the use of another type of antihypertensive drug (eg, diuretics, vasodilators, or beta-blockers) is necessary.

Sympathomimetics: The cardiovascular effects of sympathomimetics (primarily epinephrine, norepinephrine, isoprenaline, ephedrine, phenylephrine) are increased by imipramine.

Phenytoin: Imipramine leads to a decrease in the anticonvulsant effect of phenytoin.

Quinidine: To avoid the risk of conduction disturbances and arrhythmias, tricyclic antidepressants should not be used in combination with class Ia antiarrhythmic drugs.

Indirect anticoagulants: Tricyclic antidepressants inhibit the metabolism of indirect anticoagulants and increase their half-life. This leads to an increased risk of bleeding, so careful medical supervision and monitoring of prothrombin levels are recommended.

Hypoglycemic drugs: the concentration of glucose in the blood plasma during treatment with imipramine may change, therefore, at the beginning of treatment, at the end of it, and also when changing the dose, it is recommended to monitor the concentration of glucose in the blood.

Overdose

When taking the drug in dosages exceeding the norm, dizziness , ataxia , stupor, mydriasis , arrhythmia , repolarization disorders , arterial hypotension , cyanosis , fever , agitation, convulsions, coma , AV block , sinus tachycardia , collapse with high venous pressure , respiratory depression are possible , vomit.

Treatment includes gastric lavage using saline solution , as well as taking Activated Carbon . It is necessary to constantly monitor the ECG . Slow intravenous administration of F isostigmine salicylate : for adults 1-3 mg, for children in childhood - at an initial dosage of 0.5 mg, it is increased if necessary with monitoring of the function of the cardiovascular system and nervous system to 2 mg. If necessary, F isostigmine is administered every half hour or hour, the dose being selected individually.

If there are appropriate indications, symptomatic treatment with anticonvulsants : Diazepam or short-acting barbiturates . The latter are contraindicated if the patient has recently received MAO inhibitors .

Antishock measures include intravenous injections of plasma replacement solutions , glucocorticoids , and oxygen therapy .

In case of hyperthermia, cold rubdowns are used .

Overdose of the drug Melipramine, symptoms and treatment

Symptoms: dizziness, agitation, ataxia, convulsions, stupor, coma, mydriasis, sinus tachycardia, arrhythmia, AV block, repolarization disorder, collapse (with high venous pressure), hypotension, respiratory depression, cyanosis, vomiting, fever. Treatment: in case of suspected overdose of imipramine, immediate hospitalization with constant observation for at least 72 hours is necessary. There is no specific antidote. Supportive and symptomatic therapy is indicated. Due to the anticholinergic effect, gastric emptying is delayed for ≥12 hours; Therefore, first of all, it is necessary to remove the drug from the stomach. It is necessary to rinse the stomach or induce vomiting, take activated charcoal. Monitoring of cardiovascular system function indicators, as well as blood gas and electrolyte composition should be carried out. If necessary, anticonvulsant therapy is used (iv diazepam, phenytoin, phenobarbital, as well as inhalation anesthesia and muscle relaxants). You can use mechanical breathing or an artificial pacemaker. Plasma-substituting solutions and drip infusions of dopamine and dobutamine are administered. The need for resuscitation measures rarely occurs. Neither hemodialysis nor peritoneal dialysis is effective due to the low concentration of imipramine in the blood plasma. Forced diuresis is also ineffective due to the large volume of distribution of the drug. Severe bradycardia, asystole, and epileptic seizures have been associated with the use of physostigmine; Thus, in case of imipramine overdose, the use of physostigmine is not recommended.

Interaction

The use of the drug together with MAO inhibitors . This combination can cause excessive agitation, pressure , coma , convulsions, and hyperthermia . An interval of at least 2 weeks must be maintained between taking these medications.

Combination with m-anticholinergics leads to the summation of the anticholinergic effects of drugs.

Interaction with thyroid hormone adrenergic action, which provokes tachyarrhythmia and angina .

Combination with adrenergic agonists increases the likelihood of tachycardia , arterial hypertension and arrhythmia due to inhibition of catecholamine inactivation .

The drug reduces the antihypertensive effect of alpha-blockers and central alpha-adrenergic , as well as the anticonvulsant effect of Phenytoin .

The sedative effect of Melipramine increases under the influence of ethanol and drugs that depress the nervous system. Benzodiazepine derivatives and phenothiazines activate anticholinergic and sedative effects.

The biotransformation of the active substance Melipramine slows down under the influence of inhibitors of microsomal oxidation enzymes . In addition, they increase its half-life, which increases the antidepressant effect and toxicity of the drug.

Special instructions for the use of the drug Melipramine

The therapeutic effect of Melipramine develops gradually - over 2-4 weeks from the start of treatment. Therefore, maintenance treatment should be continued for at least 3, sometimes up to 6 months, until a significant improvement in the patient’s condition occurs. The use of Melipramine should be discontinued gradually - sudden discontinuation of therapy can lead to the appearance of symptoms such as nausea, headache, discomfort, anxiety, sleep disturbances, arrhythmia, extrapyramidal symptoms such as speech difficulties, especially in children. Before starting to use Melipramine, it is necessary to determine the functional state of the liver, kidneys, cardiovascular system, blood glucose levels, blood pressure, and hemogram parameters. If electroconvulsive therapy is used, Melipramine should not be administered. When treating with MAO inhibitors, it is necessary to take a break of 3-4 weeks before using Melipramine. This prevents the occurrence of seizures, increased blood pressure or body temperature. When switching after therapy with Melipramine to the use of MAO inhibitors, you should also take a break for several days. During the entire course of treatment with Melipramin, you should not drink alcoholic beverages. If persistent constipation or difficulty urinating during treatment occurs, you should inform your doctor. You must be very careful if epileptic seizures were noted before or during treatment with Melipramin. It is possible that other medications should be prescribed to prevent seizures. Due to the sedative effect of Melipramine, when using it, you should not drive vehicles, operate machinery, or engage in activities that require increased attention.

Melipramin's analogs

Level 4 ATC code matches:
Doxepin

Ladisan

Ludiomil

Anafranil

Amitriptyline

The main analogues of Melipramin as psychotropic drug: Ketilept , Anafranil , Tranquesipam . In addition, this drug belongs to the sedatives ; this group also includes Phenobarbital , Vernison , Bromizoval .

Reviews about Melipramine

Reviews of Melipramine on forums indicate that the drug is successfully used to treat depression of various origins, obsessive-compulsive disorders , and panic disorders . Patients report that its effect develops gradually. Effectiveness becomes noticeable after a few weeks.

Reviews for enuresis are also mostly positive. As a rule, the drug in this case is given to children. There are reports of some side effects (mostly nausea or drowsiness ), but those who have taken this drug say that all negative reactions are mild and go away with a decrease in dosage.

Drug interactions Melipramine

When using Melipramine, it should be taken into account that:

atropine and similar drugs increase the incidence of side effects of Melipramine;
CNS depressants and alcohol enhance the sedative effect of Melipramine; benzodiazepines and weak neuroleptics increase the sedative and anticholinergic effect of Melipramine;
enzyme stimulants (alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs) increase the breakdown of imipramine, reduce its level in the blood plasma and thus reduce its antidepressant effect;
cimetidine, methylphenidate, oral contraceptives, steroids, antipsychotics, selective serotonin uptake inhibitors reduce the breakdown of imipramine and therefore increase its antidepressant effect and toxicity;
tricyclic antidepressants increase the level of antipsychotic agents in the blood plasma (due to competitive binding by liver enzymes);
thyroid hormones enhance the antidepressant effect of imipramine;
Imipramine reduces the hypotensive effect of adrenergic blockers (for example, guanethidine) and α2-adrenergic receptor agonists (clonidine, methyldopa);
imipramine enhances the pressor effect of sympathomimetics (primarily epinephrine, norepinephrine);
Anticholinergics (phenothiazine derivatives, antiparkinsonian drugs, antihistamines, atropine, biperiden): the combined use of any of these substances and imipramine may lead to anticholinergic effects, as well as increased side effects (for example, paralytic ileus). Patients receiving this combination therapy require close monitoring and dosage adjustments should be made carefully;
sympathomimetics (mainly epinephrine, norepinephrine, isoprenaline, ephedrine, phenylephrine): combined use with imipramine can lead to increased effects on the cardiovascular system;
Quinidine: Concomitant use of this antiarrhythmic drug and tricyclic antidepressants should be avoided. During the period of combined therapy, the risk of cardiac conduction disturbances and arrhythmia increases;
oral anticoagulants: tricyclic antidepressants may inhibit the catabolism of oral anticoagulants, which may lead to an increase in the half-life of the latter, and as a result, an increased risk of bleeding. It is recommended to monitor prothrombin concentrations during treatment;
Antidiabetic agents: Changes in blood glucose concentrations may occur during treatment with imipramine. Regular monitoring of blood glucose levels is recommended at the beginning and completion of treatment, as well as during dose titration.

Melipramine price, where to buy

The price of Melipramin in tablets is about 380-410 rubles. Tablets also cost about 410 rubles. The price of Melipramine in the form of a solution can be from 380 rubles.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine

Pharmacy Dialogue

Melipramine (tablet p/o 25 mg No. 50) Egis
428 rub. order

Pharmacy24

Melipramine 25 mg No. 50 tablets ZAT FZ Yegis, Ugorshchina
107 UAH. order