Ludiomil

Ludiomil – the tetracyclic psychotropic drug of well balanced antidepressive action improving mood, eliminating excitement, uneasiness and psychomotor block.

Form of release and structure

• Tablets, film coated, 10 mg: round, with slanted edges, slightly biconvex, light yellow color, a kernel – white; on one of the parties an engraving of "CG", on another – "CO" (on 10 pieces in blisters, 5 blisters in a cardboard pack);
• Tablets, film coated, 25 mg: round, with slanted edges, slightly biconvex, gray-orange color, a kernel – white; on one of the parties an engraving of "CG", on another – "DP" (on 10 pieces in blisters, 3 or 10 blisters in a cardboard pack);
• Concentrate for preparation of solution for infusions: transparent colourless liquid (on 5 ml in ampoules, 10 ampoules in a cardboard pack).

Structure of 1 tablet, film coated:

• Active ingredient: Maprotilinum a hydrochloride – 10 or 25 mg;
• Auxiliary components: lactoses monohydrate, starch prezhelatinizirovanny corn, calcium phosphate, silicon dioxide colloid anhydrous, magnesium stearate, talc, stearic acid;
• Cover: gipromelloza, talc, polysorbate, titanium dioxide, dye ferrous oxide yellow; in addition as a part of tablets of 25 mg – dye ferrous oxide red.

Structure of 1 ml of a concentrate for preparation of solution for infusions:

• Active ingredient: Maprotilinum Methansulfonas natricum – 5 mg;
• Auxiliary components: metansulfonovy acid, Mannitolum, water for injections.

Indications to use

• Depressions: involutional and endogenous, reactive, psychogenic and neurotic (including an exhaustion depression), masked, somatogenic, and also a menopauzny (climacteric) depression;
• The depressive disturbances of mood which are characterized by a dysphoria, irritability or uneasiness;
• Condition of apathy (especially for patients of advanced age);
• Complaints of somatic or psychosomatic character at patients with uneasiness and/or a depression.

Contraindications

• The expressed disturbances of work of kidneys;
• The expressed disturbances of work of a liver;
• Urination delay (for example, as a result of prostate diseases);
• The pathologies which are followed by a reduced threshold of convulsive readiness or a convulsive syndrome (alcoholism, brain injuries of any origin);
• Closed-angle glaucoma;
• Endocardiac blockade, acute (second) stage of a myocardial infarction;
• Simultaneous therapy by monoamine oxidase inhibitors (MAO);
• Acute intoxication somnolent, psychotropic substances or alcohol;
• Hypersensitivity to medicine components;
• Cross hypersensitivity to tricyclic antidepressants.

At pregnancy Ludiomil is applied when the estimated advantage of therapy considerably exceeds risks for a fruit. At purpose of drug pregnant women need to cancel it at least in 7 weeks prior to possible delivery (if it allows a condition of the pregnant woman) to avoid development in newborns of an asthma, a lethargy, irritability, tachycardia, arterial hypotension, spasms, nervous excitement and a hypothermia.

Due to the hit of Maprotilinum in breast milk, at a lactation it is necessary to stop either use of drug, or breastfeeding.

Route of administration and dosage

Ludiomil the patient needs to be in process of therapy under observation of the doctor.

The mode of dosing is selected individually, taking into account a condition of the patient and his reaction to Maprotilinum. For example, it is allowed to raise an evening dose due to simultaneous decrease day, or to appoint all daily dose to 1 reception in the afternoon.

After registration of essential decrease in degree of manifestation of symptoms it is possible to try to reduce a drug dose. But if the condition of the patient because of it worsens, the dose should be raised to initial immediately.

Pill is taken inside, swallowing entirely and washing down with enough liquid.

The recommended dosing mode:

• Depressions of average and moderate degree of manifestation (generally at out-patient treatment): on 25 mg 1-3 times a day or 25-75 mg of 1 times a day, depending on symptomatology and efficiency of treatment;
• The expressed depressions (generally at treatment in a hospital): on 25 mg 3 times a day or 75 mg of 1 times a day; in case of need the daily dose is recommended to be raised gradually to maximum – 150 mg, taken for 1 time or divided into several receptions, depending on efficiency of treatment and portability of drug;
• Other depressive disturbances of mood, and also for children, teenagers and patients of advanced age: on 10 mg 3 times a day or 25 mg of 1 times a day; in case of need a daily dose it is possible gradually (with each reception at a small size) to raise to 25 mg 3 times a day or to 75 mg of 1 times a day, depending on efficiency of treatment and portability of drug.

The maximum daily dose (150 mg) cannot be exceeded.

The concentrate for preparation of solution for infusions Ludiomil can be appointed at insufficient effect of administration of drug inside, or at a depression, refractory to peroral therapy. In the form of intravenous infusions Maprotilinum is recommended in a daily dose from 25 mg to 100 mg.

For preparation of infusion solution of 25-50 mg of Maprotilinum (from 5 to 10 ml of a concentrate (1-2 ampoules)) part in 250 ml of glucose or isotonic solution of sodium of chloride, infusion time – 1,5-2 hours; for higher dose of-75-150 mg of Maprotilinum (from 15 to 30 ml of a concentrate (3-6 ampoules)) part in 500 ml of glucose or isotonic solution of sodium of chloride, infusion time – 2-3 hours.

On reaching sure positive dynamics of symptoms, as a rule, for 1-2 weeks, it is necessary to pass to a peroral form of medicine.

The initial dose of 25 mg (1 ampoule) divorced in 250 ml of glucose or normal saline solution, introduction time – is recommended 1,5-2 hours to elderly patients (60 years are more senior) for infusion. At further therapy, in case of need, depending on reaction to treatment and portability of drug, a daily dose about 50-75 mg (2-3 ampoules) divorced in 250-500 ml of glucose or normal saline solution, introduction time – are allowed to increase 2-3 hours gradually.

In case of a sharp dose decline or sudden drug withdrawal development of undesirable side reactions, including a withdrawal is possible.

Clinical experience of use of Ludiomil in children's age is limited therefore the mode of dosing needs to be considered as approximate recommendations. Teenagers if necessary are allowed to use drug in the same dose, as well as the adult.

Side effects

Side effects characteristic both for Ludiomil, and for other tricyclic antidepressants:

• Mental status (central and peripheral nervous system): often – feeling of fatigue, drowsiness; sometimes – concern, increase in appetite, drowsiness in the afternoon, feeling of tension, feeling of alarm, a maniacal state, aggression, a hypomaniacal state, memory disturbances, sleeplessness, sleep disorders, nightmares, disturbances of concentration of attention, strengthening of a depression; seldom – confusion of consciousness, a delirium, nervousness, hallucinations (it is preferential at advanced age); in some cases – depersonalization, activation of symptoms of psychosis;
• Neurologic status (central and peripheral nervous system): often – a headache, slight dizziness, a myoclonus, a melkorazmashisty tremor; sometimes – a dysarthtia, paresthesias (feeling of a pricking, numbness), muscular weakness, dizziness; seldom – an ataxy, spasms, an akathisia; in some cases – dyskinesia, changes of indicators of the electroencephalogram, an ataxia;
• Anticholinergic reactions: often – dryness in a mouth; sometimes – perspiration, inflows, a lock, misting of sight, disturbance of an urination, accommodation disturbance; in some cases – caries, stomatitis;
• Cardiovascular system: sometimes – heartbeat, sinus tachycardia, orthostatic hypotension, clinically insignificant changes of an ECG (an interval of ST or a tooth of T) at the patients who earlier did not have deviations from heart; seldom – increase in arterial pressure, arrhythmia; in some cases – faints, disturbances of endocardiac conductivity (blockade of legs of a ventriculonector, expansion of the QRS complex, change of an interval of PQ);
• Alimentary system: sometimes – discomfort in a stomach, nausea, vomiting; seldom – increase in level of liver enzymes (transaminases, alkaline phosphatases), diarrhea; in some cases – hepatitis with jaundice or without;
• Dermatological reactions: sometimes – a photosensitization, allergic skin answers (urticaria, rash), occasionally with fever; in some cases – a purpura, hypostases (the general or local), an itch, a skin vasculitis, a multiformny erythema, an alopecia;
• Endocrine system and metabolism: sometimes – increase in body weight, disturbance of a potentiality and libido; in some cases – a galactorrhoea, increase in mammary glands, a syndrome of inadequate secretion of vasopressin;
• Respiratory system: in some cases – a bronchospasm, an allergic alveolitis with an eosinophilia or without;
• System of a hemopoiesis: in some cases – an agranulocytosis, an eosinophilia, a leukopenia, thrombocytopenia;
• Sense bodys: in some cases – disturbances of flavoring feelings, a sonitus, a nose congestion;
• Another: sometimes owing to sudden cancellation or a bystry dose decline – abdominal pains, nausea, vomiting, diarrhea, feeling of alarm, a headache, sleeplessness, irritability, strengthening of a depression or depressive disturbances of mood concerning which treatment was carried out (usually effects it is passing, are poorly expressed and are not always accurately connected with a dose of drug and its level in a blood plasma, pass after the termination of reception of Maprotilinum or a dose decline; it is often difficult to distinguish side reactions from symptoms of a depression, such as sleep disorders, general weakness, nervousness, feeling of alarm, dryness in a mouth, a lock).

At development of serious side effects, for example, from the central and peripheral nervous system, Ludiomil is required to be cancelled.

Special instructions

By standard classification of mental diseases in the diagnostic and statistical guide to mental diseases – DSM-IV and the international statistical classification of diseases – MKB-10, states listed in the section "Indications" are determined as follows: depressive episode, recurrent depressive frustration or big depression.

At patients with schizophrenia against the background of treatment by tricyclic antidepressants the psychotic symptomatology can become aggravated, also at cyclic bipolar disorders in a depressive phase of a disease (against the background of therapy by tricyclic antidepressants) maniacal or hypomaniacal episodes were noted. At development of such complications Maprotilinum dose decline can be required, up to cancellation, and purpose of neuroleptics.

The increased probability of suicide actions in case of heavy depressions can remain before considerable remission. Both at children, and at adults, at a depression the suicide behavior and/or strengthening of a depression, and also other psychopathological symptoms irrespective of can be observed, they receive antidepressants or not. By results of short-term researches of patients of children's and teenage age for which the depression and other psychiatric disturbances was diagnosed, it was revealed that reception of antidepressants can increase risk of suicide behavior and suicide thoughts. Occasionally antidepressants can be the cause of an aggravation of suicide tendencies (intentions).

At all stages of therapy careful monitoring of the patients accepting drug on any of indications is required. Also it is necessary to study a clinical picture regarding an aggravation of symptoms, suicide actions and other psychopathological symptoms, especially at the beginning of a course or at dosing correction. It is necessary to consider the possibility of change of the mode of therapy, up to Ludiomil cancellation, especially, if such changes appeared suddenly, are brightly expressed or were not noted before administration of drug.

The main objective at Ludiomil use – achievement of therapeutic effect with use of drug in the smallest effective dose. It is especially significant for teenagers, 18 years at incomplete processes of growth are more senior than patients and elderly people. At these categories of patients the autonomic nervous system is usually unstable and reaction to Maprotilinum is more expressed.

Electroconvulsive therapy during use of Ludiomil can be carried out only under careful medical observation.

There are separate data on change in peripheral blood of number of leukocytes at therapy by Ludiomil in this connection periodic control of this indicator is necessary, the special attention concerning such symptoms as pharyngalgias or fever is also required. Implementation of these recommendations in the first months of therapy is the most urgent and at long treatment during which in addition it is necessary to make control of indicators of function of kidneys and a liver.

In the presence in the anamnesis of data on the increased intraocular pressure, heavy chronic locks or a delay of outflow of urine, especially in case of a prostatauxe, Maprotilinum is recommended to be applied with care. As drug exerts some impact inherent to tricyclic antidepressants which can promote, for example, development of paralytic intestinal impassability (especially at advanced age or at patients of a hospital), it needs to be applied with care, and at formation of a lock it is necessary to take the appropriate measures. It is impossible to exclude anticholinergic influence inherent in tricyclic antidepressants: reduction of a slezootdeleniye and relative increase in amount of slime in the lacrimal liquid that can promote damage of an epithelium of a cornea when carrying contact lenses.

At a hyperthyroidism, and also to the patients accepting drugs of hormones of a thyroid gland because of a possibility of increase in frequency of side effects from cardiovascular system, it is necessary to use drug with care.

Long therapy by antidepressants can be the cause of caries of teeth therefore in the course of treatment Ludiomil recommends to undergo systematically sanitation at the stomatologist.

It is necessary to warn the anesthesiologist before carrying out local or general anesthesia about Ludiomil use. Continuation of a course of therapy by Maprotilinum more safely in comparison with those problems which can arise because of sharp drug withdrawal just before operation. Relatives and trustees, both children, and the adults accepting antidepressants (irrespective of indications), it is necessary to warn that for patients constant observation because of risk of other psychopathological symptoms, including suicide behavior on which it is necessary to inform the attending physician immediately is required.

Medicinal interaction

• Monoamine oxidase inhibitors (MAO) – there is a probability of the expressed medicinal interactions leading to development of a hyper pyrexia, tremor, generalized clonic spasms, a delirium, up to a lethal outcome (it is important to observe an interval at least of 2 weeks between use of MAO inhibitors and Ludiomil);
• The substances exerting impact on transfer of excitement in adrenergic synapses: бетанидин, Reserpinum, гуанетидин, a clonidine and alpha Methyldopum – Maprotilinum can reduce or even completely to block their anti-hypertensive action (if along with therapy by Ludiomil it is necessary to treat arterial hypertension, it is necessary to use substances/drugs of other type (vazodilatator, diuretics or β-adrenoblockers)))))))))), not undergoing the expressed biotransformation; besides, it must be kept in mind that the sudden refusal of reception of Ludiomil can provoke the expressed arterial hypotension);
• Sympathomimetics: noradrenaline or Norepinephrinum, adrenaline or Epinephrinum, ephedrine, изопреналин and Phenylephrinum (including cases when they are a part of the local anesthetics, for example, which are applied in stomatology, or a thaw in a nose) – Maprotilinum can exponentiate cardiovascular reactions (the monitoring of patients including control of arterial pressure and a cordial rhythm, and also careful selection of a dose is necessary);
• Anticholinergic drugs: fenotiazina, antiparkinsonichesky means, atropine, Biperidinum, antihistamines – potentiation of their action on an eye pupil, the central nervous system, a bladder and intestines is possible;
• Antiarrhytmic means (quinidine, etc.) – their anticholinergic action can be synergistic to Maprotilinum with the expressiveness depending on doses (such combination is not recommended);
• The main groups of tranquilizers – increase in plasma of concentration of Maprotilinum, reduction of the threshold of convulsive readiness and development of spasms is possible; Maprotilinum with thioridazine can cause development of heavy arrhythmias;
• The medicinal drugs / substances activating microsomal enzymes of a liver: carbamazepine, oral contraceptives, barbiturates – strengthening of metabolism of Maprotilinum and, respectively, decrease in efficiency of drug is possible (it is in case of need recommended to reconsider a dosage of the specified means); besides, increase in blood serum of concentration of carbamazepine or Phenytoinum, and increase of side effects inherent to them is possible that can demand correction of doses;
• Methylphenidate – can lead to increase in concentration of tricyclic antidepressants in a blood plasma and to strengthening of their action;
• β-adrenoblockers, characterized by considerable biotransformation (propranolol, etc.) – increase in a blood plasma of concentration of Maprotilinum is possible (in need of such combination important regularly to determine Maprotilinum level in plasma and to adjust its dose);
• Coumarinic derivatives – strengthening of anticoagulating action because of inhibition of their metabolism in a liver is possible (it is recommended to trace a prothrombin time, and in case of need – to lower an anticoagulant dose);
• Derivatives of sulphonylurea or insulin – potentiation of their hypoglycemic action is possible (patients with a diabetes mellitus need regular monitoring of level of glucose in blood, both at the beginning of a course of treatment, and after its termination);
• Fluoxetine or флувоксамин – can be led to essential increase in level of Maprotilinum in blood and to development of the corresponding side effects (because of a long elimination half-life of selective serotonin reuptake inhibitors these side effects can long remain);
• The alcohol, barbiturates and other means having the oppressing influence on TsNS – their influence on an organism can be more expressed;
• Benzodiazepines – their sedative action can amplify;
• Cimetidinum – inhibits metabolism of some tricyclic antidepressants owing to what their concentration in blood increases and the frequency of undesirable reactions increases (vision disorders, dryness in a mouth) (about similar interaction with Maprotilinum it was not reported, but it is impossible to exclude that at their simultaneous use reduction of a dose of Ludiomil can be required).

Terms and storage conditions

To store in the place unavailable to children, at a temperature not above 30 °C.

Period of validity – 5 years.