Melipramine is a derivative of dibenzoazepine; tricyclic antidepressant.
Release form and composition
Melipramin dosage forms:
- Solution for intramuscular injection: transparent, colorless (possible greenish-yellow hue), odorless (2 ml in colorless glass ampoules, 5 ampoules in blisters, 2 cartons in a carton);
- Film-coated tablets: round, biconvex, red-brown in color, with a matte surface, with almost or no smell (50 each in dark glass bottles, in a cardboard bundle 1 bottle);
- Dragee: lenticular shape, brown, with a shiny surface, with almost or no smell (50 each in dark glass bottles, in a cardboard bundle 1 bottle).
In 1 ml of solution contains:
- Active ingredient: imipramine hydrochloride - 12.5 mg;
- Auxiliary components: sodium sulfite anhydrous, sodium chloride, sodium disulfite, ascorbic acid, water for injection.
1 tablet contains:
- Active ingredient: imipramine hydrochloride - 25 mg;
- Auxiliary components: magnesium stearate, lactose monohydrate, povidone K25, crospovidone and talc;
- The composition of the shell: magnesium stearate, hypromellose, Dimethicone E1049 39%, cosmetic dye red-brown (a mixture consisting of dyes iron red oxide, iron yellow oxide and black oxide black).
1 dragee contains:
- Active ingredient: imipramine hydrochloride - 25 mg;
- Auxiliary components: magnesium stearate, gelatin, talc, macrogol 35 000, titanium dioxide (E171), glycerol 85%, lactose monohydrate, sucrose, iron dye red oxide (E172).
Indications for use
All dosage forms are used to treat the following diseases:
- Depression and depression of various etiologies (psychogenic, organic, endogenous), accompanied by ideatory and motor retardation;
- Obsessive compulsive disorder;
- Panic disorder.
In the form of tablets and pills, in addition, Melipramine is prescribed to children older than 6 years with bed-wetting (for short-term adjuvant therapy in cases where organic causes of the disorder are excluded).
For all dosage forms:
- Manic episodes;
- Heart rhythm disorder;
- Violation of intracardiac conduction;
- Angle-closure glaucoma;
- Urinary retention;
- Severe renal and / or liver dysfunction;
- The use of monoamine oxidase inhibitors;
- Pregnancy and breastfeeding;
- Hypersensitivity to the components of the drug or other tricyclic antidepressants from the group of dibenzoazepine.
- Acute and subacute periods of myocardial infarction;
- Acute intoxication with opioid analgesics, hypnotics and other drugs that have a depressant effect on the central nervous system;
In the form of a solution, Melipramine, in addition, is contraindicated in heart failure, diabetes mellitus in the stage of decompensation, benign prostatic hyperplasia.
In the form of tablets, the drug is also not prescribed to patients with lactase deficiency, galactose intolerance, glucose / galactose malabsorption syndrome.
The solution is not used in pediatrics. Tablets and pills are not prescribed to children under the age of 6 years in the treatment of bed-wetting, and up to 18 years in the treatment of panic disorder and depression.
With care, Melipramine in the form of tablets and dragees should be used in the following cases:
- Acute porphyria;
- Chronic alcoholism;
- Bipolar disorder;
- Bronchial asthma;
- Oppression of bone marrow hematopoiesis;
- Angina pectoris;
- Heart failure;
- After myocardial infarction;
- Violation of the motor function of the gastrointestinal tract;
- Mild and moderate violations of the liver and / or kidneys;
- Intraocular hypertension;
- Tendency to constipation;
- Children and old age.
Dosing and Administration
Solution Melipramine is intended for intramuscular administration.
On the first day, 25 mg of imipramine is administered 3 times a day. Further, depending on the circumstances, the dose may be increased. The maximum permissible daily dose is 100 mg. From the 7th day of treatment, the dose is gradually reduced, replacing one injection with one tablet / tablet inside. By day 13, the patient should be fully transferred to oral administration of the drug in a dose of 25 mg 4 times a day. If a relapse of the disease occurs, it is possible to reappoint Melipramine intramuscularly.
Older people at the beginning of treatment prescribed lower doses.
Tablets and dragees Melipramin are inside. The doctor determines the specific dose and frequency of administration individually for each patient, depending on the type of disease, the nature and severity of symptoms. Treatment is always started with minimum doses, gradually increasing them until the smallest effective maintenance dose is selected. With special care, dose titration is performed by the elderly and patients under 18 years of age.
Recommended dosing regimens for treating depression:
- Patients aged 18-60 years undergoing outpatient treatment: 25 mg from 1 to 3 times per day. If necessary, the dose is gradually increased to 150-200 mg / day by the end of the first week of treatment. The average maintenance dose is 50-100 mg / day;
- Patients aged 18-60 years undergoing treatment in a hospital (i.e., with severe disease): the initial dose is 75 mg per day, if necessary, it is increased daily by 25 mg until the maximum daily dose of 200 mg is reached (in exceptional cases - 300 mg);
- Patients over the age of 60: treatment begins with the smallest possible dose, gradually increasing it (optimally within 10 days) to 50-75 mg / day. This dose is maintained throughout the entire treatment period.
Therapy of panic disorders begin with the lowest possible dose, because in this group of patients, an increased incidence of side effects was observed. In the future, the daily dose is gradually increased to 75-100 mg (in exceptional cases, to 200 mg). The duration of treatment is determined individually, but is not less than 6 months. In the event of anxiety at the beginning of the use of the drug, benzodiazepines are additionally prescribed - their dose is gradually reduced as the condition improves.
In case of bedwetting, the drug is prescribed to children not younger than 6 years old, only as an adjuvant therapy, and provided that organic pathologies are excluded.
Recommended daily doses depending on the age / weight of the child:
- 6-8 years / 20-25 kg - 25 mg;
- 9-12 years / 25-35 kg - 25-50 mg;
- Above 12 years old / more than 35 kg - 50-75 mg.
At the beginning of treatment, it is recommended to prescribe the lowest dose of the above ranges. Take the drug should be 1 time per day after meals before bedtime. If night enuresis occurs in the early evening hours, then the daily dose can be divided into 2 doses - during the day and at night. The maximum duration of treatment is 3 months. Exceeding these doses is possible only if after 1 week of treatment a satisfactory response is not observed.
The maximum allowable daily intake for children is 2.5 mg / kg.
Depending on the clinical picture of the disease, the maintenance dose may be reduced.
In all cases, after the end of the course of therapy, Melipramine is canceled gradually.
- Central nervous system: very often - tremor; often - delirious confusion (especially in elderly patients with Parkinson's disease), headache, dizziness, transition from depression to mania or hypomania, hallucinations, agitation, paresthesias, sleep disorders, fatigue, increased anxiety, insomnia, anxiety, orientation disorders, violations of potency and libido; infrequently - activation of psychotic symptoms, convulsions; rarely - aggressiveness, ataxia, myoclonus, extrapyramidal symptoms, speech disorders;
- Laboratory indicators: often - increased transaminase activity;
- Cardiovascular system: very often - changes on the electrocardiogram and sinus tachycardia without clinical significance (changes in the ST segment and T wave) in patients with normal cardiac activity, hot flashes, orthostatic hypotension; feeling of heartbeat, disturbance of conductivity (blockade of a bunch of Gis, expansion of an interval of PR and QRS), arrhythmias; rarely, increased blood pressure, cardiac decompensation, peripheral vasospastic reactions;
- Blood system: rarely - thrombocytopenia, leukopenia, purpura, agranulocytosis, eosinophilia;
- Endocrine system: rarely - inadequate secretion of antidiuretic hormone syndrome, galactorrhea, an increase in the mammary glands, a decrease or increase in plasma glucose concentration;
- Gastrointestinal tract: very often - dry mouth, constipation; often nausea and / or vomiting; rarely - indigestion, lesion of the tongue, stomatitis, paralytic ileus, hepatitis, not accompanied by jaundice;
- Urinary system: often - urination disorders;
- Metabolism and nutrition: very often - an increase in body weight; often - anorexia; rarely, weight loss;
- Skin: very often - increased sweating, often - allergic skin reactions (rash on the skin, urticaria); rarely - hair loss, itching, photosensitivity, petechiae, edema (local or generalized);
- The organ of vision and hearing: very often - blurred visual perception, disturbance of accommodation; rarely - mydriasis, glaucoma; frequency unknown - tinnitus;
- Other: rarely - allergic alveolitis (including with eosinophilia), weakness, hyperpyrexia, systemic anaphylactic reactions; in patients older than 50 years, an increase in the frequency of bone fractures.
There were reports of the occurrence of suicidal thoughts and behaviors during treatment with Melipramine and in the early stages of its withdrawal.
In case of abrupt discontinuation of therapy, withdrawal symptoms develop: extrapyramidal disorders, irritability, headache, insomnia, nausea, arrhythmia.
During treatment it is important to remember that the therapeutic effect is observed at least 1-3 weeks after the start of the drug. Maintenance dose should be taken at least 3 months.
Patients with suicidal tendencies in the initial period of therapy require careful medical supervision.
When prescribing Melipramine to patients with epilepsy, their condition should be carefully monitored, since in the first days of treatment, imipramine can cause an epileptic seizure.
At the start of panic disorder therapy, a paradoxical increase in psychomotor anxiety is possible. If this condition does not go away within 2 weeks, the use of drugs of benzodiazepine derivatives is necessary.
In the case of bipolar depression, imipramine may cause the patient to enter the manic phase.
The entire period of treatment is recommended to systematically carry out a general blood test, evaluate indicators of liver function, monitor the electrocardiogram and blood pressure.
Patients taking Melipramine are not allowed to drink alcohol, and at the beginning of therapy it is recommended to refrain from performing any potentially dangerous types of work, including driving a car. In the future, the degree of limitation is determined individually for each patient.
Melipramine should not be administered concomitantly with antiarrhythmic drugs, since such a combination can lead to impaired conductivity and arrhythmia.
Imipramine reduces the antihypertensive effect of adrenergic neuron blockers (betanidin, guanethidine, clonidine, reserpine, methyldopa). Therefore, if necessary, you should appoint a different type of antihypertensive drugs, for example, vasodilators, diuretics, or beta-blockers.
It is recommended to avoid combination of Melipramine with monoamine oxidase inhibitors (MAO), since these drugs have a synergistic effect, and their peripheral noradrenergic effects can reach toxic levels, leading to delirium, agitation, myoclonus, hyperpyrexia, seizures, hypertensive crisis and coma. For safety reasons, imipramine can be used no earlier than 3 weeks after discontinuation of MAO inhibitors (with the exception of the reversible MAO inhibitor, moclobemide, in this case, a break of 24 hours is sufficient). A similar period should be observed when prescribing an MAO inhibitor to a patient receiving imipramine. In this case, treatment should begin with small doses, gradually increasing them under the control of clinical effects.
In the application of Melipramin with the following drugs should be especially careful, because there is a possibility of undesirable interaction reactions:
- Inhibitors of microsomal liver enzymes: a decrease in metabolism and an increase in plasma concentration of imipramine are possible;
- Preparations of thyroid hormones: enhancement of the antidepressive effect of imipramine and its side effects on the part of the cardiovascular system;
- Estrogens, oral contraceptives: a decrease in the effectiveness of Melipramine and the development of toxic effects;
- Inductors of liver microsomal enzymes (including anti-epileptic drugs, barbiturates, meprobamate, nicotine, alcohol): increased metabolism, a decrease in the concentration of imipramine and its antidepressant effect;
- Drugs with m-anticholinergic properties (for example, bipredin, atropine, H1-histamine receptor blockers, drugs for the treatment of parkinsonism): increased antimuscarinic and side effects;
- Drugs that suppress the central nervous system (for example, barbiturates, narcotic analgesics, general anesthesia drugs, benzodiazepines): a marked increase in their action and side effects;
- Antipsychotic drugs: an increase in the concentration of imipramine in the blood plasma and the development of its side effects. When used with thioridazine, severe arrhythmias may develop;
- Sympathomimetics (mainly isoprenaline, norepinephrine, ephedrine, epinephrine, phenylephrine): enhancing their cardiovascular effects;
- Phenytoin: a decrease in its anticonvulsant action;
- Indirect anticoagulants: inhibition of their metabolism and an increase in the half-life, which leads to an increased risk of bleeding;
- Hypoglycemic drugs: changes in the concentration of glucose in the blood plasma.
Terms and conditions of storage
Keep out of reach of children, protected from light, at a temperature of 15-25 ºС.
The shelf life of the solution - 2 years, tablets and pills - 3 years.