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

Active substanceImipramineImipramine

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Imipramine

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BIOKOM, CJSC Russia

Melipramine®

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EGIS ZAO Pharmaceutical Plant Hungary

Melipramine®

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EGIS ZAO Pharmaceutical Plant Hungary

Melipramine®

solution w / m

EGIS ZAO Pharmaceutical Plant Hungary

Dosage form: & nbspsolution for intramuscular injection

Composition:

1 ampoule (2 ml solution) contains:

active substance: imipramine hydrochloride 25 mg;

Excipients: ascorbic acid, sodium disulfite, sodium sulfite anhydrous, sodium chloride for parenteral dosage forms, water for injection.

Description:

Transparent colorless or slightly colored (a greenish-yellow hue is possible) a solution without a smell.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.A.02 Imipramine

Pharmacodynamics:

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

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

Pharmacokinetics:

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

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

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

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

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

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

Indications:

All forms of depression (with and without anxiety): major depression, depressive phase of bipolar disorder, atypical depression, depressive states.

Panic states.

Contraindications:

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

Joint application with MAO inhibitors and within 3 weeks after their cancellation (see section "Interactions").

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

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

Closed-angle glaucoma.

Manic episodes.

Severe impairment of kidney and / or liver function.

Pregnancy and lactation.

Children under 18 years of age (for this dosage form of the drug).

Carefully:

Chronic alcoholism, asthma, bipolar disorder (manic-depressive illness), inhibition of bone marrow hematopoiesis, cardiovascular disease (angina, arrhythmias, heart block (except those listed under "Contraindications"), heart failure, myocardial infarction), pheochromocytoma and neuroblastoma ( the risk of hypertensive crisis), stroke, impaired motor function of the gastrointestinal tract (risk of paralytic ileus), liver and / or kidney failure, hyperthyroidism, hyperplasia n (accompanied by a delay of urine), schizophrenia (activation of psychosis is possible), epilepsy, elderly age.

Pregnancy and lactation:

Since in some cases the connection between the use of tricyclic antidepressants and fetal malformations has been recognized as possible, such drugs are contraindicated in pregnancy.

Imipramine is excreted in breast milk. Therefore, it is contraindicated during breastfeeding.

Dosing and Administration:

Parenteral administration can be used only temporarily at the beginning of the course of treatment and especially with severe depression with excitation, and also in the case when for any reason oral administration of the drug is impossible. The daily dose should not exceed 100 mg. The injection should be made deep into the muscle.

The daily dose and method of application should be set individually according to the nature and severity of the symptoms. As with the use of other antidepressants, the necessary therapeutic effect can be achieved in 2-4 weeks (possibly in 6-8 weeks) after the initiation of therapy. Treatment should begin with low doses, which should then be gradually increased to achieve the lowest effective and maintenance dose. Increasing the dose to achieve an effective level requires extreme caution in elderly patients.

Depression

Out-patient patients aged 18 to 60 years:

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

Stationary patients aged 18 to 60 years:

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

Patients older than 60 years:

These age groups can give an increased response to the above doses, so treatment should begin at the lowest possible dose. The initial dose can be gradually increased to 50-75 mg per day. It is recommended to find the optimal dose within 10 days and maintain this dose until the end of the course of treatment.

Panic disorders

Since this age group has an increased tendency to side effects of the drug, treatment should begin with the lowest possible dose. Transient increase in anxiety at the beginning of antidepressant therapy can prevent or eliminate the benzodiazepines, which can then be phased out as the elimination of the symptoms of anxiety. The dose of Melipramine® can be gradually increased to 75-100 mg per day (in exceptional cases, up to 200 mg per day). The minimum duration of treatment is 6 months. At the end of the course of treatment, gradual withdrawal of the preparation of Melipramine® is recommended.

Side effects:

The above undesirable effects do not necessarily develop in every patient. Some of these side effects depend on the dose and disappear when the dose is lowered or independently during the continuation of treatment. Some side effects are very difficult to distinguish from symptoms of depression (eg, fatigue, sleep disturbance, agitation, anxiety, dry mouth).

The introduction of imipramine should be stopped when severe neurological or psychiatric reactions occur.

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

Frequency of side effects were evaluated as follows: frequent ≥ 10%, infrequent ≥1 and <10%, rare ≥0.001-1%, very rare <0.001%

Mental effects:

Infrequent: increased fatigue, drowsiness, anxiety, increased anxiety, agitation, sleep disturbances, fluctuations from depression to hypomanic or manic state, delirium, confused consciousness (especially in elderly patients and those suffering from Parkinson's disease), disorientation and hallucinations.

Rare: activation of psychotic symptoms.

Very rare: aggressiveness.

Neurological effects:

Frequent: tremor.

Infrequent: paresthesia, headache, dizziness.

Rare: epileptic seizures.

Very rare: EEG changes, myoclonia, weakness, extrapyramidal symptoms, ataxia, speech disorders, hyperpyrexia.

The cardiovascular system:

Frequent: sinus tachycardia and clinically insignificant changes in the ECG (T wave and segment ST), orthostatic hypotension.

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

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

Anticholinergic effects:

Frequent: dry mouth, sweating, constipation, impaired vision, reduced visual acuity, hot "hot flashes".

Infrequent: violation of urination.

Very rare: mydriasis, glaucoma, paralytic intestinal obstruction.

Gastrointestinal tract:

Infrequent: nausea, vomiting, loss of appetite.

Very rare: stomatitis, defeat of the tongue.

Effects of the liver:

Infrequent: increased transaminases.

Very rare: hepatitis with or without jaundice.

Leather:

Infrequent: skin allergic reactions (rash, hives).

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

Endocrine system and metabolism:

Frequent: increase in body weight.

Infrequent: violation of libido and potency.

Very rare: increase of mammary glands, galactorrhea, syndrome of impaired secretion of antidiuretic hormone, increase or decrease in blood glucose concentration, weight loss.

Hypersensitivity:

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

Blood:

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

Other:

Noises in the ears, the development of the syndrome of "cancellation."

Overdose:

Symptoms: system dizziness, drowsiness, stupor, coma, ataxia, anxiety, agitation, hyperreflexia, rigidity of muscles, athetoid and choreiform movements, convulsions,respiratory depression, cyanosis, shock, vomiting, fever, sweating, mydriasis, oliguria or anuria, lowering blood pressure, tachycardia, arrhythmia, conduction disorders, heart failure; in very rare cases - cardiac arrest.

Treatment: If you suspect an overdose of imipramine, the patient should be hospitalized and kept under close supervision for a period of at least 72 hours. There is no specific antidote, therefore symptomatic and supportive therapy is indicated. Since the anticholinergic effect of the drug may delay the evacuation of the stomach contents of the patient (by 12 or more hours), it is necessary to rinse the stomach as soon as possible or induce vomiting, if the patient is conscious, and also to enter Activated carbon. Continuous monitoring of the cardiovascular system, gases and electrolytes of blood is required. Symptomatic treatment, it is possible to prescribe anticonvulsant therapy (for example, diazepam, phenytoin, phenobarbital, inhalation anesthetic + muscle relaxant), artificial respiration, establish a temporary pacemaker, introduce plasma substitutes, dopamine or dobutamine; in exceptional cases, there may be a need for resuscitation.

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

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

Interaction:

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

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

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

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

Anticholinergic drugs (eg, phenothiazines, anti-Parkinsonics, antihistamines, atropine, biperidene): enhance anticholinergic and side effects (eg, paralytic intestinal obstruction) when combined with imipramine. The combination with these drugs requires careful monitoring of patients and careful selection of a dose.

Medications that depress the central nervous system: a combination of imipramine with agents depressing the central nervous system (eg, opiates, benzodiazepines,barbiturates and general anesthetics) and alcohol significantly increases the main and side effects of these drugs.

Antipsychotics can increase the levels of tricyclic antidepressants in blood plasma and strengthen their main and side effects. A dose reduction may be required. Co-administration with thioridazine can cause severe arrhythmia.

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

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

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

Phenytoin: imipramine reduces the anticonvulsant effect of phenytoin.

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

Oral anticoagulants: tricyclic antidepressants inhibit the metabolism of oral anticoagulants and prolong their half-life. This increases the risk of bleeding, which is why it is recommended to monitor the level of prothrombin plasma.

Antidiabetics: the concentration of glucose in the blood can change during the course of treatment with imipramine. Therefore, it is recommended to monitor the blood glucose concentration at the beginning and end of the course of treatment, as well as when changing the dose.

Special instructions:

The therapeutic effect can occur no sooner than 2-4 weeks after the start of treatment. As with the use of other antidepressants, the later onset of a therapeutic effect means that the patient's suicidal tendencies are not immediately eliminated, and the patient needs careful medical attention before significantly improving his condition.

The minimum duration of taking a maintenance dose is 6 months. Imipramine should be withdrawn gradually, as a sudden discontinuation of its administration may cause withdrawal symptoms (nausea, headache, general malaise, anxiety, anxiety, sleep disorders, cardiac rhythm disturbances, extrapyramidal symptoms).

In patients with bipolar depression imipramine can provoke a manic state. The drug should not be taken during manic episodes.

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

Taking Melipramin® increases the risk of electroconvulsive therapy, which is why it is contraindicated during electroconvulsive therapy.

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

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

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

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

With ischemic heart disease, impaired liver and kidney function, as well as diabetes mellitus (a change in the concentration of glucose in the blood) imipramine should be used with caution.

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

Treatment of patients with hyperthyroidism or using drugs of the thyroid gland requirescareful medical control because of the increased risk of side effects on the heart in these patients.

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

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

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

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

Imipramine causes photosensitivity, therefore, during the course of treatment, intensive UV irradiation should be avoided.

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

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

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

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

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

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

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

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

The use of the preparation of Melipramine increases the risk of an accident. Therefore, it is necessary to prohibit the management of vehicles and mechanisms at the beginning of the course of treatment. In the future, the degree of restriction or prohibition should be determined by the physician for each patient individually.

Form release / dosage:Solution for intramuscular injection, 25 mg / 2 ml.

Packaging:

2 ml each in an ampoule of colorless glass with two color code rings (blue and green), as well as a white ring of the fault.

5 ampoules are placed in a contour mesh package (blister).

2 contour squeeze packs (blisters) together with the instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N014539 / 01

Date of registration:22.09.2008 / 13.01.2015

Expiration Date:Unlimited

Date of cancellation:2018-04-09

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

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

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

Information update date: & nbsp27.04.2018

Illustrated instructions

Instructions

Melipramine® (Melipramin®)