Imipramine; 5-/3-dimethylaminopropyl/-10,11-dihydro-5N-dibenzo-/b,f/azepine monohydrochloride is a derivative of dibenzoazepine. It belongs to a group of drugs called tricyclic antidepressants. It has a thymoleptic effect, improves mood, reduces the feeling of sadness. It has a concomitant stimulating effect, reduces motor retardation, increases the mental and general tone of the body. It has a central and peripheral M-anticholinergic, myotropic (spasmolytic), moderate antihistamine effect.
When used orally, imipramine is well absorbed in the gastrointestinal tract, bioavailability is 29-77%. It is quickly distributed in tissues, easily penetrates through the BBB. Selectively accumulates in the brain, kidneys, liver. The maximum plasma concentration is reached 1-2 hours after ingestion. Binding to plasma proteins - 76-95%.
Intensively metabolized in the liver. Within 24 hours, up to 40% of the taken imipramine is excreted in the urine as inactive metabolites, 1-2% - unchanged, about 20% - excreted in the bile. The half-life is 4-24 hours. Therapeutic plasma concentration is 0.05-0.16 mg / l, toxic - 0.7 mg / l, lethal - 2 mg / l.
Indications for use of the drug Melipramine
- in all forms of depression (with or without anxiety): deep depression, in the depressive phase of bipolar disorder, depression with an atypical course, depressive states, dysthymia;
- with panic disorders;
- for nocturnal enuresis (in children over 6 years of age): as a means of short-term adjunctive therapy, if organic causes are excluded.
The use of the drug Melipramin
Dragee
Daily doses should be determined individually depending on the severity and origin of the symptoms. As with other antidepressants, to achieve an adequate therapeutic effect, a course of treatment is required for at least 2-4 weeks, sometimes 6-8 weeks. It is recommended to start therapy with Melipramine at low doses and gradually increase the daily dose until a maintenance dose is reached. During the period of treatment, the minimum dose that has an effect should be determined; care is needed when determining the dose for elderly and adolescent patients (under 18 years of age).
Solution for injections
Melipramine parenterally is used to treat depressed patients in a state of high arousal or when oral administration is not possible. Depending on the patient's condition, the doctor may prescribe the administration of Melipramin injection solution only for a short time, and then switch to taking the drug in the form of a dragee.
Doses for adults
Depression .
Outpatient treatment of patients begins on the basis of a daily dose of 25 mg in a dragee or 2 ml of injection (1-3 times a day) / m. The maximum daily dose for this route of administration is 100 mg. In the future, as the patient's condition improves, you can switch to treatment with a tablet form of the drug.
This dose can be gradually increased to 150-200 mg/day over 1 week. Maintenance dose - 50-100 mg / day. In hospitalized patients with severe depression, therapy is started at a daily dose of 75 mg / day. This dose can be gradually increased by adding 25 mg each time until 200 mg / day is reached. In exceptional cases, the daily dose may be increased to 300 mg / day.
Elderly patients (over 60 years of age) and adolescents (under 18 years of age). These patients are more susceptible to the drug and may experience adverse reactions in response to standard adult doses. Therefore, the treatment of these patients should be started with the lowest dose that controls the symptoms of the disease. Further, a gradual increase in the dose is possible until the daily dose is reached - 50-75 mg. It is recommended to achieve the optimal dose within 10 days and continue treatment at the same dose.
Panic Disorders .
Patients with these disorders are more likely to develop side effects, so treatment should be initiated at the lowest possible dose. Transient attacks of more severe anxiety, observed at the very beginning of therapy with Melipramine, can be controlled with the help of benzodiazepine derivatives. This adjuvant therapy is gradually withdrawn as the symptoms of anxiety disappear. The daily dose of Melipramin is gradually increased to 75-100 mg / day (as an exception - up to 200 mg / day). The course of treatment is long, at least 6 months. The course of therapy is completed by gradually reducing the dose and discontinuing the drug.
Doses for children
Recommended such treatment regimens: children aged 6-8 years (body weight - 20-25 kg) - 25 mg / day; children 9-12 years old (body weight - 25-35 kg) - 25-50 mg / day; children over the age of 12 years (body weight 35 kg) - 50-75 mg / day.
Therapy in children is carried out mainly with Melipramin in the form of a dragee.
If a low initial dose is ineffective, to achieve an adequate therapeutic effect, the drug is used in higher doses, but within the scheme, taking into account the age of the child. In the treatment of children, it is necessary to ensure that the daily dose does not exceed 2.5 mg / kg of body weight per day. In each regimen, the lowest effective dose within the range indicated should be used. The daily dose can be given as a single dose at bedtime. If enuresis is noted in the early evening, it is recommended to divide the daily dose (one part - to the child in the afternoon in the afternoon, the other - before bedtime). The duration of the course of treatment should not exceed 3 months. The maintenance dose should be selected as the severity of symptoms decreases. Before the complete withdrawal of the drug, a gradual decrease in the daily dose is recommended.
Contraindications to the use of the drug Melipramin
Dragee Melipramin 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;
- in the treatment of 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);
- the presence of narrow-angle glaucoma.
Melipramine Injection Solution should not be administered to children under 6 years of age.
Side effects of Melipramin
The most common side effects of the drug are drowsiness, postural hypotension, tachycardia and atropine-like symptoms: dry mouth, constipation, urinary retention, blurred vision, disturbance of 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 convulsions;
- 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 toes;
- gastrointestinal: very rarely - hepatitis with impaired liver function, icteric 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 (after 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, orgasm disturbance;
- very rarely, mainly in the elderly, - changes in peripheral blood parameters during laboratory tests.
Special instructions for the use of the drug Melipramin
The therapeutic effect of Melipramin 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. Melipramin should be discontinued gradually - sudden withdrawal of therapy may lead to symptoms such as nausea, headache, discomfort, anxiety, sleep disturbance, arrhythmia, extrapyramidal symptoms, such as speech difficulties, especially in children.
Before starting the use of Melipramin, it is necessary to determine the functional state of the liver, kidneys, cardiovascular system, blood glucose levels, blood pressure, and hemogram parameters. In the case of electroshock therapy, Melipramin 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 Melipramin 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.
In the event of persistent constipation or difficulty urinating during treatment, you should inform your doctor.
It is necessary to be very careful if epileptic seizures were noted before or during treatment with Melipramin. It is possible that other drugs should be prescribed to prevent seizures.
Due to the sedative effect of Melipramin, when using it, you can not drive vehicles and work with mechanisms or engage in activities that require increased attention.
Melipramine drug interactions
When using Melipramin, it should be borne in mind that:
- atropine and similar drugs increase the incidence of side effects of Melipramin;
- CNS depressants and alcohol enhance the sedative effect of Melipramine; benzodiazepines and weak antipsychotics increase the sedative and anticholinergic effect of Melipramine;
- enzyme stimulants (alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs) increase the breakdown of imipramine, reduce its plasma level and thus reduce its antidepressant effect;
- cimetidine, methylphenidate, oral contraceptives, steroids, antipsychotics, selective serotonin reuptake inhibitors reduce the breakdown of imipramine and therefore increase its antidepressant effect and toxicity;
- tricyclic antidepressants increase the level of antipsychotic agents in 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 (eg 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 can lead to an anticholinergic effect, as well as an increase in side effects (for example, paralytic ileus). Patients receiving this concomitant therapy require constant monitoring, and doses for them should be selected carefully;
- sympathomimetics (mainly epinephrine, norepinephrine, isoprenaline, ephedrine, phenylephrine): combined use with imipramine may lead to increased effects on the cardiovascular system;
- quinidine: the simultaneous use of this antiarrhythmic agent and tricyclic antidepressants should be avoided. During the period of combined therapy, the risk of impaired cardiac conduction and the occurrence of arrhythmia increases;
- oral anticoagulants: tricyclic antidepressants can inhibit the catabolism of oral anticoagulants, which can lead to an increase in the half-life of the latter, and as a result, an increased risk of bleeding. It is recommended during treatment to control the concentration of prothrombin;
- antidiabetic agents: during treatment with imipramine, changes in the concentration of glucose in the blood may occur. Regular monitoring of blood glucose levels is recommended at the beginning and end of treatment, as well as during dose selection.
Melipramine overdose, 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 is necessary with constant observation for at least 72 hours. 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 wash the stomach or induce vomiting, take activated charcoal. It is necessary to monitor indicators of the function of the cardiovascular system, as well as gas and electrolyte composition of the blood. If necessary, anticonvulsant therapy is used (in / in diazepam, phenytoin, phenobarbital, as well as inhalation anesthesia and muscle relaxants). You can use hardware breathing, an artificial pacemaker. Enter plasma-substituting solutions, drip infusions of dopamine and dobutamine. The need for resuscitation is rare. Neither hemodialysis nor peritoneal dialysis is effective due to low plasma concentrations of imipramine. Forced diuresis is also ineffective due to the large volume of distribution of the drug. The use of physostigmine has been associated with severe bradycardia, asystole, and epileptic seizures; thus, physostigmine is not recommended for overdose of imipramine.
Melipramin storage conditions
At a temperature of 15-25 °C.
List of pharmacies where you can buy Melipramin:
- Saint Petersburg
Antidepressant
Active substance
Imipramine hydrochloride (imipramine)
Release form, composition and packaging
Film-coated tablets red-brown, round, biconvex, with a matte surface, odorless or almost odorless.
Excipients: lactose monohydrate - 110.5 mg, magnesium stearate - 1.5 mg, crospovidone - 3 mg, talc - 3 mg, (K-25) - 7 mg.
Shell composition: hypromellose - 2.61 mg, magnesium stearate - 0.24 mg, iron dye red oxide - 0.68 mg, iron dye black oxide - 0.12 mg, dimethicone (E1049 39%) - 0.35 mg.
50 pcs. - dark glass bottles (1) - packs of cardboard.
pharmachologic effect
- manic episodes;
- severe impairment of kidney and / or liver function;
- urinary retention;
- angle-closure glaucoma;
- age up to 6 years in the treatment of bedwetting and up to 18 years in the treatment of depression and panic disorder (lack of sufficient clinical experience);
- pregnancy and lactation;
- intolerance to galactose, congenital lactase deficiency or malabsorption and galactose syndrome (tablets contain lactose monohydrate).
Dosage
The dose and frequency of administration are determined individually, depending on the nature and severity of symptoms. As with the use of other antidepressants, at least 2-4 weeks (possibly 6-8 weeks) are required to achieve a therapeutic effect. Treatment should begin with low doses and gradually increase them to select the lowest effective maintenance dose. Dose titration to achieve efficacy requires special care in the elderly and in patients under 18 years of age.
Depression
Outpatients aged 18-60:
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:
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, there may be a pronounced response to the above doses, therefore, treatment should be started 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 reach the optimal dose within 10 days and maintain this dose throughout the 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. A transient increase in anxiety at the start of antidepressant treatment can be prevented or treated with benzodiazepines, the dose of which is gradually reduced as anxiety symptoms improve. The dose of Melipramine may be gradually increased up 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 cancel Melipramin gradually.
Children:
It is recommended to use the lowest dose from the above dose range. The daily dose is recommended to be taken once after meals at 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, Melipramin should be discontinued gradually.
Side effects
The side effects listed below may not necessarily occur in all patients. Some of the side effects are dose-dependent, so they disappear after dose reduction or spontaneously as treatment continues. Some side effects are difficult to distinguish from symptoms of depression (eg, fatigue, sleep disturbance, agitation, anxiety, dry mouth).
The use of imipramine should be temporarily discontinued with the development of severe neurological or mental reactions.
Elderly patients are especially sensitive to m-anticholinergic, neurological, mental or cardiovascular effects. The ability to metabolize and eliminate the drug may be reduced, leading to the risk of increasing its plasma concentrations.
Undesirable effects observed with the use of the drug Melipramine are classified by body systems and are listed below as very often (≥1/10), often (≥1/100 and<1/10); нечасто (≥1/1000 и <1/100); редко (≥1/10000 и <1/1000); очень редко (<1/10000), частота неизвестна (не может быть установлена по имеющимся данным).
In each of the frequency groups, adverse effects are listed in descending order of severity.
Laboratory research: often - increased activity of transaminases.
From the side of the cardiovascular system: very often - sinus tachycardia and ECG changes that do not have clinical significance (changes in the T wave and ST segment) in patients with normal heart activity, orthostatic hypotension, hot flashes; often - arrhythmias, conduction disturbances (expansion of the QRS complex
and PR interval, 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, anxiety, 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 - a violation 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, indigestion, stomatitis, tongue damage, hepatitis, not accompanied by jaundice.
From the urinary system: often - urination disorders.
From the side of the skin: very often - increased sweating; often - allergic skin reactions (skin rash, urticaria); rarely - edema (local or generalized), photosensitivity, itching, petechiae, hair loss.
From the endocrine system: rarely - an increase in the mammary glands, galactorrhea, a syndrome of inappropriate secretion of antidiuretic hormone, an 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 a decrease in blood pressure, allergic alveolitis (pneumonitis) with or without eosinophilia. People older than 50 who take antidepressants have an increased incidence of bone fractures.
During therapy with imipramine and in the early stages after discontinuation of the drug, there have been cases of suicidal thoughts and suicidal behavior.
Overdose
Symptoms:
CNS: dizziness, lethargy, stupor, coma, ataxia, anxiety, agitation, increased reflexes, muscle rigidity, athetoid and choree-like movements, convulsions.
The cardiovascular system: decrease in blood pressure, tachycardia, arrhythmia, conduction disturbances, shock, heart failure, 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 with adults, are more sensitive to acute overdose, which should be considered dangerous and potentially fatal for them.
Treatment:
Patients with suspected overdose of imipramine should be hospitalized and observed in the hospital for at least 72 hours. There is no specific antidote, treatment is mainly 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), you should install a gastric tube as soon as possible or induce vomiting (if the patient is conscious) and enter. Continuous monitoring of cardiovascular activity, gas and electrolyte composition of the blood is required. As a symptomatic treatment, anticonvulsant therapy (IV diazepam, phenobarbital, inhalation anesthetics and muscle relaxants), artificial ventilation of the lungs, installation of a temporary pacemaker, administration of plasma-substituting fluids, dopamine or dobutamine IV drip may be used, in exceptional cases, cardio- pulmonary resuscitation. Hemodialysis or peritoneal dialysis is ineffective given the low plasma concentrations of imipramine. Due to the high V d forced diuresis is also ineffective. Given reports that physostigmine can cause severe bradycardia, asystole and epileptic convulsions, its use in overdose of imipramine is not recommended.
drug interaction
MAO inhibitors: combinations with MAO inhibitors should be avoided, since 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, in which a break of 24 hours is sufficient). A drug-free period of three weeks should also be observed when transferring a patient from imipramine to MAO inhibitors. Treatment with MAO inhibitors or imipramine should be initiated at low doses and gradually increased while closely monitoring clinical effects.
Inhibitors of microsomal liver enzymes: when used together with imipramine, inhibitors of cytochrome P450 isoenzyme 2D6 may lead to a decrease in the metabolism of the drug and, thus, lead to an increase
plasma concentrations of imipramine. Inhibitors of this type include drugs that are not substrates of cytochrome P450 isoenzyme 2D6 (cimetidine, methylphenidate), as well as drugs that are metabolized by this isoenzyme (i.e., many other antidepressants, phenothiazines, class Ic antiarrhythmic drugs (propafenone, flecainide)). All antidepressants related to selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 isoenzyme 2D6 of varying potency. Accordingly, compliance is required
caution when combining imipramine with these drugs, as well as when transferring a patient from antidepressants, which are selective serotonin reuptake inhibitors, to imipramine (and vice versa), especially in cases with fluoxetine (given the long half-life of this drug).
Tricyclic antidepressants may increase plasma concentrations
blood 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 are sporadically observed in women who take oral contraceptives or estrogen preparations together and tricyclic antidepressants. Thus, the combined use of these drugs requires caution, and with the development of toxic effects, the dose of one of the drugs should be reduced.
Microsomal liver enzyme inducers(alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs, etc.) increase the metabolism of imipramine and reduce its plasma concentration and antidepressant effects.
Preparations with m-anticholinergic properties(eg, 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 (eg, 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 (eg, narcotic analgesics, benzodiazepines, barbiturates, drugs for general anesthesia) and alcohol leads to a pronounced increase in the effects and side effects of these drugs.
Antipsychotic drugs may increase the plasma concentration of tricyclic antidepressants, thus increasing side effects. Dose reduction may be required. Co-administration 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 care.
Sympatholytics: imipramine may reduce the antihypertensive effect of commonly used adrenergic neuron blockers (guanethidine, betanidine, reserpine, clonidine, methyldopa). Thus, in patients requiring co-administration of drugs for the treatment of arterial hypertension, the use of a different type (for example, diuretics, vasodilators or β-blockers) is necessary.
Sympathomimetics: the cardiovascular effects of sympathomimetics (mainly 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 antiarrhythmics.
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 the prothrombin content is 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, as well as when changing the dose, it is recommended to control the concentration of glucose in the blood.
special instructions
Suicide/suicidal ideation or clinical deterioration
Depression is associated with an increased risk of suicidal ideation, self-harm, and suicide (suicidal events). This risk persists until a pronounced remission occurs. Since improvement may not occur during 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. The frequency of suicides increases in children and young people under 24 years of age.
Other mental conditions in 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, in the treatment of patients with other psychiatric disorders, the same precautions should be observed as in the treatment of patients with major depressive disorder.
Patients with a history of suicidal events or patients with significant suicidal ideation prior to initiation of therapy are at increased risk of suicidal thoughts or suicide attempts, and therefore require careful monitoring during therapy. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric 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 watch for any clinical deterioration, suicidal behavior or thoughts, and unusual changes in behavior and seek immediate medical attention if these symptoms are present.
The therapeutic effect can be expected no earlier than 2-4 weeks of treatment. As with other antidepressants, the late onset of the therapeutic effect means that the patient's suicidal tendencies will not be eliminated immediately, so the patient needs careful medical supervision until significant improvements are achieved.
Maintenance dose therapy should be continued for at least 6 months.
Therapy with imipramine should be discontinued gradually, since abrupt discontinuation of the drug may cause "withdrawal" symptoms (nausea, headache, fatigue, anxiety, 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 a history of spasmophilia or epilepsy require careful medical supervision and adequate anticonvulsant therapy.
Serotonin syndrome can occur with the use of drugs that inhibit the reuptake of serotonin (tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, etc.), or blocking the metabolism of serotonin (MAO inhibitors). Serotonin syndrome can develop when they are combined or when combined with other drugs that enhance the action 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 cases with fluoxetine (given the long half-life of this drug). Serotonin syndrome, which includes three groups of symptoms - motor, autonomic and mental disorders - develops within hours or days after starting treatment with a serotonin mimetic agent or increasing its dose. Treatment includes the abolition of serotonergic agents and the implementation of symptomatic measures.
Melipramine increases the risk associated with electroconvulsive therapy, so the use of the drug in electroconvulsive therapy is not recommended.
In the form of a paradoxical reaction, patients with panic disorders may experience an increase in anxiety in the first few days of therapy. Increased anxiety usually subsides spontaneously within 1–2 weeks and can be treated with benzodiazepine derivatives if needed.
Patients with psychosis may experience increased restlessness, anxiety, and agitation at the start of tricyclic antidepressant therapy.
Due to the m-anticholinergic effect, the use of imipramine requires careful medical supervision in glaucoma, prostatic hyperplasia and severe constipation, since treatment can lead to an increase in the severity of these symptoms. In contact lens wearers, decreased tear production and accumulation of mucus can damage the corneal epithelium.
Imipramine should be used with caution in ischemic heart disease, impaired liver and kidney function, and in diabetes mellitus (changes in blood glucose concentration).
Treatment of patients with tumors of the adrenal glands (pheochromocytoma or neuroblastoma) requires special care, since imipramine can provoke the development of a hypertensive crisis.
Therapy of patients with hyperthyroidism and patients using thyroid hormone preparations requires careful medical supervision, given the increased risk of cardiovascular adverse reactions in these patients.
Given the increased risk of arrhythmia and lower blood pressure during general anesthesia, the anesthesiologist should be informed before the operation that the patient is taking imipramine.
In some cases, the development of eosinophilia, leukopenia, agranulocytosis, thrombocytopenia and purpura was reported during treatment with imipramine, so regular monitoring of blood test parameters is required.
With long-term antidepressant therapy, 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, therefore, especially at the beginning of treatment, lower doses are required. Imipramine causes photosensitivity, so exposure to intense sunlight should be avoided during treatment.
In patients with a predisposition and / or elderly patients, imipramine can cause m-anticholinergic (delirious) syndrome, which stops within a few days after discontinuation of the drug.
Melipramine film-coated tablets contain lactose monohydrate. During therapy with imipramine, it is forbidden 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 blood circulation or arterial hypotension);
- liver function (especially in patients with liver disease);
- indicators of peripheral blood (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).
Influence on the ability to drive a car and work with mechanisms
The use of the drug Melipramine leads to an increased risk of accidents, therefore, at the beginning of therapy, driving and working with mechanisms should be prohibited. Later, the degree and duration of these restrictions are determined by the doctor individually.
Pregnancy and lactation
Since in certain cases the possibility of a relationship between the use of tricyclic antidepressants and fetal developmental disorders has been established, the use of the drug during pregnancy is contraindicated.
Imipramine is excreted in breast milk, therefore, the use of the drug during lactation is contraindicated.
Application in childhood
The drug is contraindicated under the age of 6 years in the treatment of bedwetting and under 18 years of age in the treatment of depression and panic disorder (lack of sufficient clinical experience).
The drug should only be given to children over 6 years of age. exclusively as a temporary adjuvant therapy for nocturnal enuresis with the exclusion of organic pathology.
6-8 years (with a body weight of 20-25 kg): 25 mg / day.
9-12 years old (with a body weight of 25-35 kg): 25-50 mg / day.
Over 12 years old and body weight above 35 kg: 50-75 mg / day.
The daily dose in children should not exceed 2.5 mg/kg of body weight.
Use in the elderly
In elderly patients, imipramine can cause m-anticholinergic (delirious) syndrome, which stops within a few days after discontinuation of the drug.
Side effects may be more severe in elderly patients, therefore, especially at the beginning of treatment, lower doses are required.
Terms of dispensing from pharmacies
The drug is dispensed by prescription.
Terms and conditions of storage
The drug should be stored out of the reach of children at a temperature not exceeding 25°C.
Shelf life - 3 years. Do not use after the expiration date stated on the packaging.
Melipramine is a drug used to treat nervous and depressive conditions. This drug belongs to the group of antidepressants.
The drug is available in the form of tablets in film shells, round and biconvex shape. One tablet contains 25 mg of the active ingredient imipramine hydrochloride.
The preparation also contains such active substances:
- lactose monohydrate (110 mg);
- povidone K25 (7 mg);
- talc (3 mg);
- magnesium stearate (1.5g);
- crospovidone (3 mg).
pharmachologic effect
The drug is able to provide m-anticholinergic, antihistamine and antispasmodic effects. The active substance is not able to inhibit MAO.
The sedative effect comes on gradually (from 1 to 3 weeks after taking). The active ingredient has a stimulating effect on
central nervous system. The drug is able to remove inhibitory barriers (which reduce motor activity) and improve mood.
Melipramine also has analgesic, antiarrhythmic and antidiuretic effects. The active substance of the drug increases the synaptic saturation of norepinephrine and increases the composition of serotonin in the central nervous system.
The drug inhibits ventricular conduction, as a result of which the further development of arrhythmias is prevented. With the help of the drug, a balance is achieved in the work of serotonergic and adrenergic transmission. The analgesic effect is achieved due to the influence on the concentration of monoamines and on the apiate receptor systems.
Pharmacokinetics means
After internal administration, all components of the drug are well absorbed in the gastrointestinal tract. During the first passage through the liver, active metabolism occurs, with the formation of desipramine. All components of the substance of the drug are excreted with feces and urine (20 and 80%, respectively).
About 6% of the active substance is excreted in unchanged form. The half-life of the drug is 19 hours.
In special clinical cases, after a single dose of the drug, it is possible to slow down the half-life (in case of overdose and in elderly patients). The degree of binding to plasma proteins is 85%.
The active component of the drug is able to accumulate in the kidneys, liver and brain. When it enters the body, the drug in the liver begins to intensively biotransform.
Mechanism of action
Melipramine is a dibenzoazepine derivative. The mechanism of action is the ability to block the reverse neuronal uptake of norepinephrine and serotonin. As a result, there is an increase in the concentration of these substances in the synapses of the central nervous system.
With prolonged use of the drug, there is a decrease in the functional activity of serotonin receptors in the brain.
Also, as a result, serotonergic transmission is normalized and its balance is restored, which was previously disturbed after depressive states.
The active ingredient has an anticholinergic effect, which leads to an increase in the ability of the bladder to stretch. The activity of alpha-adrenergic agonists is accompanied by a central blockade of serotonin uptake.
Scope of application
Indications for the use of Melipramin are quite extensive:
Restrictions for prescribing funds
Contraindications to the use of Melipramin tablets:
- individual intolerance;
- hypersensitivity to the components of the drug;
- atony of the bladder;
- children's age (up to six years);
- pregnancy;
- renal and hepatic deficiency;
- tachycardia;
- congestive heart failure;
- predisposition to seizures;
- the presence of schizophrenia;
- early post-infarction period;
- the presence of prostate adenoma;
- the presence of glaucoma.
Instructions for use
The daily dose of the drug is set individually, depending on the type of disease and its severity.
depressive states
Patients aged 18 to 60 years, at the beginning of treatment, are prescribed 25 mg of Melipramin per day, with a multiplicity of doses of 2-3 times.
Further, for six days, the doses are gradually increased to 150-200 mg per day. For elderly patients (over 60 years) and adolescents (less than 18 years) age, the smallest possible doses of the drug are prescribed, with a gradual increase to 50-75 mg.
Panic disorders and neuroses
In this case, the lowest possible dose is prescribed. During the week, it should be increased to 75-10 mg per day. In exceptional cases, the dose is increased to 200 mg per day.
The average course of therapy with Melipramin is six months.
Overdose and additional instructions
With an overdose of the drug, the following symptoms appear:
- dizziness;
- convulsions;
- lowering blood pressure;
- arrhythmia;
- fever and sweating.
In cases of manifestation of one of the above symptoms, the patient must be hospitalized during the first 72 hours after an overdose is suspected. Due to the lack of a special antidote, supportive and symptomatic therapy is used.
Side effects of the drug are manifested in the form of orthostatic hypotension, fever, increased blood pressure. So side of the hematopoietic system, there are such undesirable effects as: leukopenia, eosinophilia, thrombocytopenia, agranulocytosis (very rarely).
During therapy with Melipramin, it is strictly forbidden to take alcohol. The same applies to the period of pregnancy and breastfeeding.
The drug is contraindicated in hepatic and renal insufficiency. The medication is not prescribed for children under six years of age.
Interaction with other drugs
The combination of Melipramine and MAO inhibitors causes a synergistic effect, which subsequently enhances the noradrenergic effect.
Simultaneous use with oral contraceptives reduces the antidepressant effect and contributes to the development of a toxic effect.
Co-administration with liver enzyme inducers enhances the metabolism of the active substance and reduces its saturation in the blood plasma. Anticholinergic drugs increase the risk of side effects.
Unfortunately, depression and mental disorders are quite common problems. In no case should they be discarded or ignored, since they require therapy, quite often medication. There is a drug that helps to cope with a number of emotional disorders, at least the reviews indicate this. "Melipramine" is a medicine that is very popular in psychiatry and some other branches of medicine. So how does it affect the body?
What is included? Description of the release form
There are two forms in which Melipramin is produced - tablets and a solution for internal administration. The main active substance of the drug is imipramine. Each tablet contains 25 mg of this component, as well as a number of excipients, including dimethicone, lactose monohydrate, magnesium stearate, as well as iron oxide, crospovidone and hypromellose.
As for the solution, 1 ml contains 12.5 mg of imipramine, as well as auxiliary components, in particular sodium chloride, sodium disulfite, ascorbic acid, anhydrous sodium sulfate and purified water as a base.
Description of the main properties of the drug
This tool is quite evidence of this research and reviews. "Melipramine" in addition has other properties, in particular, painkillers and sedatives. The drug also acts as an antidiuretic.
The active component of the drug increases the concentration of norepinephrine in the synapses, and also increases the level of serotonin in the tissues of the central nervous system. The drug slows down ventricular conduction, as a result of which it stops the development of arrhythmia. Also, the active substance blocks histamine H2 receptors in the cells of gastric tissues, reduces acid secretion, due to which it also has an antiulcer effect.
As a rule, at first, the tablets cause a sedative effect, which, as the therapy progresses, disappears.
List of indications for admission
There are many cases in which this medicine can help, which is confirmed by the reviews. "Melipramin" is prescribed to patients who are diagnosed with the following problems:
- depressive states of endogenous origin;
- depression that occurs against the background of neuroses, psychopathy, menopausal changes;
- asthenodepressive syndrome;
- reactive depression;
- withdrawal syndrome when stopping the use of products containing cocaine;
- panic disorder;
- migraine;
- narcolepsy;
- neuropathies that occur against the background of diabetes mellitus;
- postherpetic neuralgia;
- severe pain of a chronic nature;
- severe headaches that cannot be stopped with other medicines;
- bulimia nervosa;
- some forms of enuresis.
The drug "Melipramin": instructions for use
As you can see, this medicine is quite strong, and therefore it is impossible to use it arbitrarily. Only a specialist after a complete diagnosis can prescribe the drug "Melipramin" to the patient. The instructions for use contain only some general information.
When it comes to the treatment of adults, the daily dose ranges from 75 to 200 mg of the active substance, depending on the patient's condition. If the desired therapeutic effect is absent, the dose is gradually increased to 200-300 mg. This amount of the drug is divided into 3-4 doses.
How to take "Melipramin"? Doctors recommend taking pills in the morning and afternoon. If taken in the evening, the medicine may cause insomnia. The course of treatment is from 4 to 6 weeks. In the future, maintenance therapy is needed, which lasts about the same time, but the patient is gradually reduced in dose.
What are the features of treating children with Melipramin? Tablets are also taken in the morning and at lunchtime, but the dose, of course, is different. The initial daily amount of the active ingredient is 10 mg, after which it is gradually increased to 20 (children 6-8 years old), 25 (8-14 years old) or 50-100 mg (children over 14 years old).
Are there any contraindications for admission?
In some cases, taking the drug may be unjustified or even dangerous. Here is a list of contraindications for therapy:
- hypersensitivity to the constituent components of the drug;
- taking medications - MAO inhibitors;
- acute intoxication of the body with ethyl alcohol;
- drug intoxication;
- depression of the central nervous system;
- poisoning with sleeping pills;
- period of pregnancy and lactation;
- conduction disturbances inside the ventricles of the heart;
- myocardial infarction;
- angle-closure glaucoma;
- children's age (up to 6 years).
The drug can be taken with bronchial asthma, chronic alcoholism, renal failure, heart disease, but in such cases it is necessary to carefully monitor the patient's condition. Relative contraindications also include stroke, vascular disorders, problems with hematopoiesis, impaired motility of the digestive tract, as well as pheochromocytoma, epilepsy, liver failure, schizophrenia, prostatic hyperplasia, thyrotoxicosis and
List of possible adverse reactions
Some patients develop some side effects while taking the pills:
- from the digestive system: dryness of the oral mucosa, heartburn, constipation, vomiting;
- on the part of the senses: decreased clarity of vision, paresis of accommodation, glaucoma, impaired taste perception, tinnitus;
- from the side of the heart and blood vessels: tachycardia, arrhythmia, ECG changes;
- from the nervous system and psyche: depersonalization, confusion, insomnia, conditions, difficulty urinating, hallucinations, problems with concentration, headaches, asthenia, drowsiness, disorientation, psychomotor agitation, increased depression, dizziness;
- other possible complications include hyperhidrosis, a sharp change in body weight, decreased potency, cholestatic jaundice, urticaria, metabolic disorders, and swelling of the testicles in men.
Regardless of what changes you notice after starting therapy, if alarming symptoms occur, you should definitely consult a doctor.
The drug "Melipramin": analogues
Not all patients are suitable for this medicine. It is worth noting that the modern market offers a fairly large selection of drugs with similar properties. Sometimes a doctor may prescribe medications such as Imizin or Impramine. These are kind of synonyms that contain the same active substance. The list of analogues also includes "Apo-Imipramine" and "Prioygan-25".
Another important point for patients is the cost of Melipramin. Its price is quite affordable. A pack of 50 tablets will cost about 360-450 rubles, which is not so much, especially when compared with some analogues.
Melipramine- antidepressant, non-selective monoamine reuptake inhibitor.
The mechanism of therapeutic action of imipramine is not fully understood. Imipramine, a dibenzoazepine derivative, is a tricyclic antidepressant. It inhibits the reuptake of norepinephrine and serotonin in the synapse, which are released in response to irritation of nerve cells, promotes noradrenergic and serotonergic transmission. Imipramine also inhibits muscarinic and histamine (H 1) receptors, due to which it exhibits anticholinergic and mild sedative effects.
The antidepressant effect develops gradually: the optimal therapeutic effect occurs after 2-4 (possibly 6-8) weeks after the start of treatment.
Pharmacokinetics
.The drug undergoes extensive first-pass metabolism in the liver: its main pharmacologically active metabolite, desipramine (desmethyl-imipramine), is formed by demethylation. Plasma concentrations of imipramine and desipramine fluctuate greatly. After 10 days of treatment with imipramine at a dose of 50 g 3 times a day, the equilibrium concentration of imipramine in blood plasma ranged from 33 to 85 ng/ml, and the concentration of desipramine ranged from 43 to 109 ng/ml. Due to reduced metabolism, plasma concentrations are usually higher in elderly patients than in younger patients.
The volume of distribution of imipramine is 10-20 l/kg.
Both active compounds are highly bound to plasma proteins (imipramine: 60-96%, desipramine: 73-92%).
Imipramine is excreted in the urine (about 80%) and feces (almost 20%) mainly as inactive metabolites. Excretion with urine and feces in unchanged imipramine and its active metabolite, desipramine, is 5-6% of the dose taken. After taking a single dose, the half-life of imipramine is approximately 19 hours and varies between 9 and 28 hours, and can be significantly increased in the elderly and in case of overdose.
Imipramine crosses the placental barrier into breast milk.
Indications for use
All forms of depression (with or without anxiety): major depression, depressive phase of bipolar disorder, depression with atypical course, depressive states, dysthymia; panic disorder; nocturnal enuresis in children older than 6 years; as a temporary adjuvant therapy if organic causes are excluded.Mode of application
Depression.Melipramine solution for injection should be used only temporarily for the treatment of depressed patients in a state of severe agitation or when oral administration is not possible. The solution for injection should be used at the beginning of treatment, and then switch to the use of tablets as soon as the patient's condition allows.
The daily dose should be determined individually, depending on the severity of the symptoms. The initial dose is 25 mg (2 ml) 1-3 times a day, which can be increased to a maximum daily dose of 100 mg (4 ml).
The daily dose should be determined individually, depending on the severity and nature of the symptoms.
As with other antidepressants, a 2-4-week course of treatment (sometimes 6-8 weeks) is required to achieve the desired therapeutic effect. Treatment should begin with low doses, which should be gradually increased to determine the minimum effective, and then the maintenance dose. To achieve an effective dose, dose titration should be carried out with extreme caution in elderly patients.
The initial dose should not exceed 100 mg. The drug should be injected deeply into.
For the treatment of nocturnal enuresis in children, it is recommended to use Melipramin tablets. If oral administration is not possible for some reason, then parenteral administration of the drug should be considered.
The drug can only be used in children over 6 years of age and exclusively for the temporary, auxiliary treatment of nocturnal enuresis, if organic changes are excluded.
It is recommended to use the lowest dose within the above dose range. It is advisable to prescribe the daily dose at one time before bedtime. If enuresis occurs in the early evening, it is recommended to divide the daily dose into two doses (one part of the dose is given to the child in the afternoon, the other at bedtime).
Recommended doses:
children 6-8 years old (body weight - 20-25 kg) - 25 mg / day
children 9-12 years old (body weight - 25-35 kg) - 25-50 mg / day
children over 12 years of age (body weight> 35 kg) - 50-75 mg / day.
Higher recommended doses of the drug are justified only if, after one week of treatment with lower doses, a satisfactory effect is not achieved.
The daily dose for children should not exceed 2.5 mg/kg of body weight.
The duration of the course of treatment should not exceed 3 months.
Depending on changes in the clinical picture, the maintenance dose may be reduced. At the end of therapy, Melipramin should be discontinued gradually.
Side effects
Side effects of the drug Melipramine listed below are not necessarily observed in every patient. Some side effects are dose-dependent and disappear with dose reduction or disappear on their own during treatment. Some side effects are difficult to distinguish from symptoms of depression (eg, fatigue, sleep disturbance, agitation, restlessness, dry mouth).If serious neurological or psychiatric side effects occur, imipramine should be discontinued.
Elderly patients are particularly sensitive to the anticholinergic, neurological, psychiatric, or cardiovascular effects of this drug. The ability to withdraw drugs in patients of this age group may be reduced, which threatens to increase the concentration of the drug in the blood plasma.
Side effects with the same frequency are listed in decreasing order of severity.
Deviation from the norm, identified in laboratory studies
Increased transaminase levels.
From the side of the cardiovascular system. Sinus tachycardia and clinically insignificant ECG changes (T wave and ST sector) in patients with normal cardiac function; arrhythmias, conduction disturbances (expansion of the QRS complex and PR interval, blockade of the legs of the bundle of His), palpitations; cardiac decompensation, myocardial infarction.
From the vascular system. Orthostatic hypotension, hot flashes; increased blood pressure, peripheral vasospastic reactions, stroke.
From the blood and lymphatic system. Agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.
From the side of the nervous system. Tremor paresthesia, headache, dizziness, epileptic seizures; extrapyramidal symptoms, ataxia, myoclonus, speech disorders, EEG changes, impaired coordination, insomnia, nocturnal delirium.
From the organs of vision. Violation of accommodation, blurred vision; glaucoma, mydriasis.
From the organs of hearing and balance. Noise in ears.
From the digestive system. Constipation, dry mouth, vomiting, nausea, paralytic ileus, stomatitis, darkening of the tongue, epigastric discomfort, diarrhea, abdominal pain.
From the urinary system. Violation of urination, urinary retention.
From the skin and subcutaneous tissues. increased sweating; allergic skin reactions (rash, urticaria) edema (local or generalized), photosensitivity, itching, petechiae, hair loss.
From the endocrine system. Breast enlargement, galactorrhea, syndrome of inappropriate antidiuretic hormone secretion, increased or decreased blood sugar levels.
Nutritional and metabolic disorders. Weight gain loss of appetite, darkening of the tongue, changes in taste; weight loss.
Systemic disorders and reactions at the injection site. Rare: hyperpyrexia, weakness.
From the immune system. Systemic anaphylactic reactions, including arterial hypotension, allergic alveolitis (pneumonitis) with or without eosinophilia.
From the digestive system. Hepatitis without jaundice, jaundice.
Mental disorders.
Delirious confusion (especially in elderly patients with Parkinson's disease), disorientation and hallucinations, fluctuations between depression and hypomania or mania, agitation, restlessness, increased anxiety, fatigue, drowsiness, sleep disturbances, libido and potency disorders; activation of psychotic symptoms aggressiveness, illusions.
During therapy with imipramine or shortly after its termination, cases of suicidal thinking and suicidal behavior have been described (see section "Peculiarities of use").
Sudden discontinuation of the drug after prolonged use can lead to the development of such symptoms of the system: nausea, headache, weakness.
Epidemiological studies conducted in patients under the age of 50 show an increased risk of bone fracture in patients receiving serotonin reuptake inhibitors and tricyclic antidepressants.
Contraindications
Contraindications to the use of the drug Melipramine are: hypersensitivity to the active or any excipient, or to other tricyclic antidepressants of the benzodiazepine group; treatment with MAO inhibitors (see section "Interaction with other drugs and other forms of interaction"); recent myocardial infarction. conduction disorder; Heart arythmy; manic episodes; severe kidney and / or liver disease; urinary retention; glaucoma (narrow angle glaucoma).Pregnancy
Since the relationship between the use of tricyclic antidepressants and fetal malformations in some cases, it was possible to use the drug Melipramine during pregnancy is contraindicated.Imipramine passes into breast milk, so the use of the drug during breastfeeding is contraindicated.
Interaction with other drugs
MAO inhibitors. Simultaneous use is contraindicated Melipramina and MAO inhibitors, since these drugs act synergistically and may increase the risk of side effects from the central and peripheral nervous systems (hypertensive crisis, hyperpyrexia, myoclonus, anxiety, convulsions, delirium, coma). For this reason, treatment with imipramine should be started no earlier than 3 weeks after the completion of therapy with MAO inhibitors (with the exception of moclobemide, a reverse MAO inhibitor, when a sufficient interval is 24 hours). A three-week break is also needed in the case of switching from imipramine therapy to treatment with MAO inhibitors. A new course of treatment with imipramine or an MAO inhibitor should be started at low doses, which can be gradually increased under close monitoring of clinical effects.Liver enzyme inhibitors. When used together with imipramine, inhibitors of the cytochrome P450 2D6 isoenzyme may reduce metabolism and thus increase the plasma concentration of imipramine. Inhibitors of this type include drugs that are not substrates of CYP2D6 (cimetidine, methylphenidate), as well as those that are metabolized by this enzyme (for example, other antidepressants, phenothiazines, type 1c antiarrhythmics (propafenone, flecainide)). Although their potency varies, all SSRI-type antidepressants are inhibitors of CYP2D6. Therefore, caution should be exercised when using imipramine concomitantly with these drugs, as well as when transferring a patient from therapy with an antidepressant of the SSRI type to imipramine (and vice versa), especially when it is fluoxetine (due to the long half-life of this drug). Tricyclic antidepressants may increase plasma concentrations of antipsychotics (due to competitive interaction with liver enzymes).
Oral contraceptives, estrogens. With the combined use of oral contraceptives or estrogens with tricyclic antidepressants in women, a decrease in the antidepressant effect and the development of toxic effects of the drug were sporadically observed. Therefore, caution should be exercised with the simultaneous use of these drugs, and in the event of the appearance of toxic effects, reduce the dose of one or another drug.
Liver enzyme inducers (alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs) increase the metabolism of imipramine and reduce its plasma level, thus reducing the severity of the antidepressant effect.
Anticholinergics (phenothiazine derivatives, antiparkinsonian agents, antihistamines, atropine, biperidene): The simultaneous use of any of these drugs and imipramine may lead to an anticholinergic effect, as well as an increase in side effects (for example, paralytic ileus).
Patients receiving such combination therapy should be under constant supervision, and doses for them should be selected with caution.
Central nervous system (CNS) depressants: Combining imipramine with CNS depressants (eg, opiates, benzodiazepines, barbiturates, general anesthetics) and alcohol markedly enhances the effects and side effects of these drugs.
Antipsychotic drugs can increase the plasma concentration of tricyclic antidepressants, thus enhancing their action and side effects. Dose reduction may be required. Co-administration with thioridazine may cause severe arrhythmias.
Thyroid hormones can enhance the antidepressant effect of imipramine, as well as its side effects on the part of the heart, so the joint appointment of these drugs requires caution.
Antiadrenergic blockers. Imipramine may reduce the hypotensive effect of antiadrenergic blockers (eg, guanethidine, betanidine, reserpine, clonidine, and α-methyldopa). Therefore, patients who need combined treatment of arterial hypertension should be prescribed antihypertensive drugs of different groups (for example, diuretics, vasodilators or β-blockers).
Sympathomimetics (mainly epinephrine, norepinephrine, isoprenaline, ephedrine, phenylephrine): simultaneous use with imipramine may lead to an increase in the effect of these drugs on the cardiovascular system.
Phenytoin: Imipramine reduces the anticonvulsant effect of phenytoin.
Quinidine: The concomitant use of this antiarrhythmic agent and tricyclic antidepressants should be avoided. During the combined use of these drugs, there is an increased risk of impaired cardiac conduction, as well as the occurrence of arrhythmias.
Oral anticoagulants: Tricyclic antidepressants may inhibit the metabolism of oral anticoagulants and prolong their half-life, which increases the risk of bleeding. Recommended close monitoring of the patient and frequent monitoring of plasma prothrombin levels.
Antidiabetic drugs: during treatment with imipramine, the concentration of glucose in the blood may change. Therefore, at the beginning and at the end of treatment with imipramine, as well as during dose selection, regular monitoring of blood sugar is recommended.
Overdose
Symptoms:From the side of the central nervous system - dizziness, drowsiness, clouding of consciousness, coma, ataxia, agitation, excitement, increased reflexes, muscle rigidity, athetoid and choree-like movements, convulsions
From the side of the cardiovascular system - arterial hypotension, tachycardia, arrhythmia, conduction disturbance, shock, heart failure, very rarely - cardiac arrest;
Others - respiratory depression, cyanosis, vomiting, fever, sweating, mydriasis, oliguria, anuria.
Treatment. In case of any suspicion of an overdose of imipramine, immediate hospitalization and close monitoring of the patient for at least 72 hours are necessary. There is no specific antidote. Treatment should be symptomatic and supportive. Since gastric emptying may be delayed (by 12:00 or more) as a result of the anticholinergic effect of the drug, the patient should first of all gastric lavage or induce vomiting (if the patient is fully conscious) and give activated charcoal more quickly. It is necessary to monitor indicators of cardiovascular function, as well as gas and electrolyte composition of the blood. As symptomatic therapy, anticonvulsant therapy (intravenously - diazepam, phenytoin, phenobarbital, as well as inhalation anesthesia + muscle relaxant), artificial lung ventilation, a temporary artificial pacemaker, administration of plasma substitutes, dopamine or dobutamine by intravenous drip infusion can be used. In exceptional cases, resuscitation may be required. Hemodialysis or peritoneal dialysis is not effective due to low plasma concentrations of imipramine. Forced diuresis is also not effective 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 an overdose of imipramine, its use is not recommended.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ° C, protected from light and out of the reach of children.Release form
Melipramine - solution for injection.Packing: 2 ml solution in ampoules; 5 ampoules in a blister pack, 2 packs in a carton box.
Compound
2 ml solution (1 ampoule) Melipramine contain imipramine hydrochloride 25 mg.Excipients: sodium chloride, sodium metabisulfite (E 223), anhydrous sodium sulfite (E 221), ascorbic acid, water for injection.
Additionally
A drug Melipramine can be used in children over the age of 6 years only for the treatment of nocturnal enuresis.Suicide / suicidal thoughts or worsening clinical signs
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide itself (suicide-related phenomena). This risk persists until remission. Since there may be no improvement in symptoms in the first few weeks of therapy, patients should be closely monitored until they appear. Clinical experience shows that the risk of suicide may increase in the early stages of recovery.
Other psychiatric disorders for which Melipramine may be prescribed may also be associated with an increased risk of suicidal events. In addition, these disturbances may accompany major depressive disorder. Therefore, in the treatment of patients with other mental illnesses, the same precautions should be observed as in the treatment of patients with major depressive disorders.
It is known that patients with a history of suicidal events, or patients who had a significant level of suicidal ideation prior to therapy, are more prone to suicidal thoughts or suicide attempts and should be closely monitored during treatment.
During the entire course of treatment, in particular in its early stages and after a change in dosage, patients should be closely monitored, especially those who are at high risk. Patients, as well as their caregivers, should be warned to watch for any deterioration in clinical signs, signs of suicidal behavior or suicidal ideation, as well as unusual changes in behavior, and seek prompt medical attention if such symptoms are detected.
The therapeutic effect can be achieved earlier than 2-4 weeks after the start of treatment. This late onset of treatment, which is common with other antidepressants, means that the patient's suicidal motives do not disappear immediately, and he requires close medical supervision until a significant improvement is achieved.
The maintenance dose should be taken for at least 6 months. The dose of imipramine should be reduced gradually, since an abrupt cessation of administration may be accompanied by withdrawal symptoms (nausea, headache, discomfort, anxiety, anxiety, sleep disorders, arrhythmia, extrapyramidal symptoms), especially pronounced in children.
In the case of bipolar depression, imipramine therapy can provoke the development of mania. The drug should not be used during manic seizures.
Like other tricyclic antidepressants, imipramine lowers the seizure threshold, so patients with epilepsy or a history of spasmophilia and epilepsy should be under medical supervision and, if necessary, receive appropriate anticonvulsant therapy.
Melipramine increases the risk of adverse events during electroconvulsive therapy, therefore it is not recommended for this type of treatment.
In the first days of therapy with tricyclic antidepressants, a paradoxical reaction and increased anxiety in patients with panic disorders are possible. Increased anxiety usually resolves on its own within 1-2 weeks, but if necessary, it can be treated with a benzodiazepine derivative. Patients with psychosis at the beginning of the course of treatment with tricyclic antidepressants may experience increased restlessness, anxiety and agitation.
Due to the anticholinergic effect of imipramine therapy, careful monitoring of patients with glaucoma, prostatic hypertrophy and severe constipation is necessary, since this compound may exacerbate these symptoms.
Imipramine and other tricyclic antidepressants increase intraocular pressure only in eyes with a local anatomical tilt - a narrow anterior chamber angle. With open-angle glaucoma, an increase in intraocular pressure is not observed. Reduced tear fluid production and mucus accumulation can damage the corneal epithelium in contact lens wearers.
Imipramine should be used with caution in patients with ischemic heart disease, impaired liver and kidney function, and diabetes mellitus (changes in blood glucose levels).
Particular caution should be observed in the treatment of patients with tumors of the adrenal glands (pheochromocytoma or neuroblastoma), since imipramine can provoke a hypertensive crisis.
When using the drug in patients with hyperthyroidism and patients taking thyroid drugs, close supervision is needed due to an increased risk of side effects from the heart in this category of patients.
Due to the potential increased risk of arrhythmia and hypotension during general anesthesia, it is important to inform the anesthesiologist before surgery that the patient is taking imipramine.
In rare cases, eosinophilia, leukopenia, agranulocytosis, thrombocytopenia and purpura have been observed during imipramine therapy, so patients taking this drug should regularly count blood cells.
With long-term therapy with tricyclic antidepressants, an increased incidence of caries was noted, so patients who take imipramine should be regularly examined by a dentist.
Side effects may be more pronounced in elderly and young patients, so people in these age groups are advised to use lower doses, especially at the beginning of the course of treatment.
Imipramine causes photosensitivity, so patients should avoid exposure to intense light during treatment.
In predisposed patients and / or patients of flying age, imipramine can cause an anticholinergic (delirious) psychosyndrome, which disappears a few days after stopping therapy.
The drug Melipramine, solution for injection contains sodium bisulfite and sodium sulfite, which can cause the development of hypersensitivity reactions and bronchospasm.
During therapy with imipramine, the intake of alcoholic beverages is contraindicated.
Before starting and regularly during the course of treatment, it is recommended to monitor the following indicators:
- blood pressure (especially in patients with unstable blood circulation or arterial hypotension)
- liver function (especially in people with liver disease)
- differential blood count (urgent - in case of fever or laryngitis, as they may be a sign of leukopenia and agranulocytosis, in other cases - before starting and regularly during treatment)
ECG (in elderly patients and those with cardiovascular diseases).
If the patient develops an increase in body temperature or sore throat, it is necessary to control the level of leukocytes, with a pathological decrease in neurophils, imipramine should be discontinued.
The ability to influence the reaction rate when driving vehicles or operating other mechanisms
When treated with Melipramin, you should not drive a car and other mechanical means or engage in activities associated with an increased risk of accidents.
Main settings
| Name: | MELIPRAMINE |
| ATX code: | N06AA02 - |
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