Clomipramine - instructions for use, doses, side effects, contraindications

auxiliaryьthe matter: microcrystalline cellulose - 37.75 mg, lactose monohydrate - 9.05 mg, croscarmellose sodium - 1,875 mg, magnesium stearate - 1,125 mg, silicon colloid dioxide 0.2 mg, film sheath: hydroxypropylmethylcellulose (hypromellose) - 1.6 mg, polyethylene glycol (macrogol) 0.4 mg, titanium dioxide (E 171) 0.97 mg, iron oxide yellow (E 172) - 0.03 mg.

Description:

Round, biconvex tablets covered with a film coat of pale yellow color. On one side is engraved "25", the other side is smooth.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

Clomipramine

Pharmacodynamics:

Clomipramine is a tricyclic antidepressant from a group of non-selective inhibitors of neuronal capture of monoamines. ABOUTblada expressed timoanalepticheskim action, refers to antidepressant balanced action (a combination of psycho-stimulating and anxiolytic, sedative actions). The mechanism of antidepressant action of clomipramine is associated with the ability to inhibit re-uptake norepinephrine and serotonin with appropriate neurons (the reverse capture of serotonin decreases more than in the case of other tricyclic antidepressants).

Antidepressant effect manifests itself in the first week of use.

Possesses expressed central and peripheral alpha-adrenoblocking, as well as M-cholin-blocking, H₁-gastamine-blocking action. Has a central analgesic, anti-bulimic action, is effective in bedwetting.

Clomipramine is characterized by a wide range of other pharmacological actions: alpha₁-adrenolitic, anticholinergic, antihistamine and antiserotonergic (blockade of 5-HT-receptors).

Clomipramine affects the depressive syndrome in general, including especially on such typical manifestations as psychomotor retardation, depressed mood and anxiety.Clinical effect is usually observed after 2-3 weeks of treatment.

Clomipramine also has a specific effect Pri obsessively-compulsive disorder, which is different from its antidepressant effect.

The action of Clomipramine in chronic pain syndromes, caused or not caused by somatic diseases, is associated with the relief of transmission of a nerve impulse mediated by serotonin and norepinephrine.

Psychostimulating effect is expressed to a lesser degree, than in imipramine, and the sedative is weaker than that of amitriptyline.

Pharmacokinetics:

Absorption - fast, practically 100 %, bioavailability is about 50%(the effect of "first passage" through the liver). After a single ingestion of 50 mg the maximum concentration in the blood (Tcmax) of clomipramine is 4 hours, and its desmethylated metabolite (which is a powerful inhibitor of norepinephrine reuptake) 4 - 24 h.

In patients who received Clomipramine in a dose of 25 mg 3 times a day, the equilibrium concentration of the drug in the plasma is created by the end of the first week of treatment and is: for clomipramine and desmethylclomipramine - 113 and 184 ng / ml, respectively, and in patients taking 75 mg once day in the evening, respectively, 70 and 81 ng / ml.

The connection with plasma proteins is 97.6 %.

The volume of distribution is 12 - 17 l / kg. Concentration in spinal fluid - 2% of that in plasma, in mother's milk - similar to plasma.

Half-life (T1/ 2) - 21 hours. In patients with depression, lengthening is possible T1 /2 to 36 hours. The kidneys are taken out 2/3 in the form of water-soluble compounds, about 1/3 - through the intestine. The amount of unchanged Clomipramine and its active metabolite, secreted by the kidneys, is no more than 1% of the dose, the rest is excreted as hydroxylated metabolites.

FarmakokinNoandspecific groups of patients

In elderly patients, regardless of the doses Clomipramine, due to a decrease in the intensity of the metabolism of Clomipramine, its concentration in the plasma is higher than in patients of a younger age. Influence of violations of the liver and kidneys on the pharmacokinetics of clomipramine has not been studied.

Indications:

Treatment of depressive conditions of different etiology, taking place with different symptoms:

- endogenous, reactive, neurotic, organic, masked, involutional forms of depression;

- Depression in patients with schizophrenia and psychopathies;

- Depressive syndromes arising in old age, caused by chronic pain fromindroma or chronic medical conditions;

- Depressive mood disorders of reactive, neurotic or psychopathic nature.

Obsessive-compulsive syndromes.
Chronic pain syndrome.
Phobias and panic disorders (attacks).
Cataplexy accompanying narcolepsy.
Nocturnal enuresis (only in patients over 10 years of age and subject to exclusion of organic causes of the disease).

Contraindications:

- Hypersensitivity to Clomipramine.

- Hypersensitivity (incl. To dibenzazepine derivatives).

- Acute poisoning with alcohol, hypnotics, sedatives and other psychotropic drugs, as well as analgesics and means for general anesthesia.

- Heart failure in the stage of decompensation.

- Acute and recovery period of myocardial infarction.

- Violations of the conduction of the heart muscle,

- Severe arterial hypertension.

- Acute liver and kidney disease, with severe impairment of functions.

- Diseases of the blood.

- Stomach ulcer and 12- the intestine in the stage of exacerbation.

- Hypertrophy of the prostate.

- Atony of the bladder.

- Pylorosthenosis, paralytic obstruction of the intestine.

- Simultaneous administration of MAO inhibitors and 2 weeks before and after the use of inhibitors, including selective MAO inhibitors of reversible action (see "Interaction with other drugs"means").

- Congenital lengthening syndrome of QT.

- Pregnancy, the period of breastfeeding.

- Children under 10 years.

Carefully:

Clomipramine should be used with a particular aboutwatchfulness in patients with epilepsy, and in the presence of other predisposing to the occurrence of a convulsive syndrome of factors, for example, brain damage of any etiology, simultaneous use of neuroleptic drugs, in the period of alcohol withdrawal or withdrawal of drugs with anticonvulsant properties (eg, benzodiazepines).

It is believed that the onset of seizures during the administration of clomipramine zdepending on the amount of the drug. In this regard, do not exceedthe recommended daily dose of Clomipramine.

FROM extreme cautionьYu should be appointed Clomipramine patients with cardiovascular diseases, first of all, with cardiovascular insufficiency, violations of intracardiac conduction (for example, atrioventricular blockade I-III degree) or arrhythmias. In such patients, as well as in patients elderly, it is necessary to regularly monitor blood pressure, function cardiovascular system and ECG.

Because the drug has anticholinergic properties, it should be used with extreme caution in patients who have a history of increased intraocular pressure, angle-closure glaucoma, or urinary retention (eg, due to diseases prostate gland).

Caution is necessary in the treatment of tricyclic antidepressants in patients with severe liver disease, as well as in patients with tumors of the adrenal medulla (for example, pheochromocytoma, neuroblastoma), as in this case, these drugs can provoke the development of hypertensive crisis.

Many patients with panic attacks at the beginning of Clomipramine treatment increase anxiety.This paradoxical increase in anxiety is most pronounced in the first days of therapy and usually subsides within two weeks.

In patients with schizophrenia receiving tricyclic antidepressants, sometimes there is an activation of psychosis. It is known that in patients with cyclical affective disorders, taking tricyclic antidepressants, during the depressive phase may develop manic or hypomanic states. In such cases, there is a need to reduce the dose of Clomipramine or in its abolition and administration of an antipsychotic. After stopping these conditions, if there are indications, treatment with clomipramine in low doses can be resumed. Before starting Clomipramine therapy, it is recommended to measure the arteriesabecause in patients with orthostatic hypotension or lability of the vascular system may aboutthere is a sharp decline blood pressure.

Because of possible cardiotoxic effects, it is necessary to observe caution in the treatment of patients with hyperthyroidism or patients receiving drugs of thyroid hormones.

In patients with liver disease, periodic monitoring of hepatic enzyme activity is recommended.

Although the changes in the level of leukocytes during the treatment with clomipramine reported only in selected cases, it is recommended that periodic study of the composition of peripheral blood and attention to symptoms such as fever and sore throat, especially in the early months of therapy or during long-term use of the drug.

Clomipramine, as well as other tricyclic antidepressants, is prescribed in combination with electroconvulsive therapy only under the condition of careful medical observation.

In predisposed patients and elderly patients, tricyclic antidepressants can provoke the development of drug psychoses, mainly at night. After the abolition of the drug the above disorders occur within a few days.

Depression is characterized by a risk of suicidal actions, which can persist until a significant remission is achievedand.

In this regard, at the beginning of treatment, a combination of Clomipramine with drugs from the benzodiazepine group or with neuroleptic drugs can be indicated.There are reports that against the background of Clomipramine reception there are fewer deaths due to overdose than with the use of other tricyclic antidepressants.

Caution is necessary when using Clomipramine in patients with chronic constipation. Tricyclic antidepressants can cause paralytic intestinal obstruction, mainly in elderly patients or in patients who are forced to comply with bed rest.

Before conducting general or local anesthesia should be warned An anesthesiologist that the patient is taking Clomipramine.

It was reported on the increase in dental caries during long-term treatment with tricyclic antidepressants. Therefore, in the case of prolonged therapy Clomipramine recommended regular examination of the patient's dentalgth.

Due to the anticholinergic effect of tricyclic antidepressants, tearing can be reduced and a relative increase in the amount of mucus in the composition of the tear fluid, which can lead to damage to the corneal epithelium in patients using contact lenses. Clomipramine should be avoided drastically, as this can lead to adverse reactions.

Pregnancy and lactation:The experience with clomipramine during pregnancy is limited. Since there are known individual reports of a possible association between the use of tricyclic antidepressants with developmental disorders of the fetus, Clomipramine should be avoided during pregnancy, except when the expected effect of the treatment of the mother clearly exceeds the potential risk to the fetus. In cases where tricyclic antidepressants were used during pregnancy until the onset of labor, new withdrawal symptoms developed during the first few hours or days, manifested by dyspnea, drowsiness, colic, irritability, hypotension or hypertension, tremor, or spasmodic events. To avoid the development of this syndrome, Clomipramine should be, if possible, gradually canceled, at least 7 weeks before the expected delivery. Since the active substance of the drug penetrates into breast milk, you should either stop breastfeeding, or gradually cancel.

Dosing and Administration:The dosage of the drug and the route of administration are selected individually, taking into account the patient's condition. The tactic of treatment is to achieve the optimal effect against the background of the use of as small as possible doses of the drug, as well as in their careful increase, especially in elderly patients and adolescents, who are generally more sensitive to Clomipramine than patients of intermediate age groups.

Assign inside (during or after eating) without chewing the tablets.

The course of treatment with clomipramine, depending on the indications, lasts from 1 to 6 months.

Depression, obsessive-compulsive syndromes and phobias

Treatment begins with the appointment of 1 tablet, coated with a shell containing 25 mg of clomipramine, 2-3 times a day. Then, during the first week of treatment, the dose of the drug is gradually increased, for example, by 25 mg every few days (depending on tolerability), until a daily dose of 4-6 tablets of 25 mg.In severe cases, the daily dose can be increased to the maximum, which is 250 mg. Once a clear improvement, select the maintenance dose of the drug, component 2-4 tablets of 25 mg.

Panic disorder, agoraphobia

Treatment begins with the use of 1 tablet containing 10 mg clomipramine, per day, possibly in combination with a drug from the benzodiazepine group. Then, depending on the tolerability of Clomipramine, its dose is increased to achieve the desired effect; after this, the drug is gradually withdrawn from the benzodiazepine group. The daily dose of Clomipramine required in these cases varies greatly from patient to patient and ranges from 25 up to 100 mg, if necessary, it can be increased to 150 mg. Recommended do not stop the course for at least 6 months, slowly reducing during this time a maintenance dose of the drug.

Cataplexy accompanying narcolepsy

The daily dose of Clomipramine is 25 to 75 mg.

Chronic Pain Syndromes

The dose of Clomipramine should be selected individually (10-150 mg in day), taking into account the concomitant use of analgesics (and taking into account the possibility of reducing their use).

Nocturnal enuresis

Initial dose of clomipramine in children aged 10-12 years is 1-2 tablets of 25 mg; in older children - 1-3 tablets of 25 mg. The use of higher doses is indicated for those patients in whom there is no clinical effect after 1 week of treatment. Usually the whole daily dose of the drug is prescribed in one session after dinner, but in cases when involuntary urination is noted in the early hours of the night, part of the dose of clomipramine is prescribed earlier, at 16 o'clock. After achieve the desired effect of treatment should continue for 1-3 months, gradually reducing the dose of clomipramine.

Elderly patients

Treatment begins with the appointment of 1 tablet Pabout 10 mg per day. Then gradually, approximately for 10 days, the daily dose of the drug is raised to the optimal level, which is 25-50 mg, and retained her On this level of before the end of treatment.

Side effects:From the nervous system

Headache, dizziness, weakness, insomnia, fear, anxiety, agitation, aggressiveness, paresthesia, small tremor, slurred speech, ataxia, hallucinations, confusion, disorientation, decreased concentration, delirium, in patients in the depressive phase may develop mania. Less often: convulsive seizures, myoclonia, extrapyramidal disorders.

From the psychic sphere: often - drowsiness, general weakness, anxiety, increased appetite; sometimes - confusion, disorientation, confusion, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, agitation, sleep disorders, manic state, hypomanic condition, aggressiveness, memory impairment, depersonalization, increased depression, attention deficit disorder , insomnia, nightmares, yawning; rarely - activation of symptoms of psychosis.

From the neurological sphere: often - dizziness, tremor, headache, myoclonus; sometimes - delirium, speech disorders, paresthesia, muscle weakness, increased muscle tone; rarely - convulsions, ataxia; in some cases - changes on the electroencephalogram, hyperpyrexia.

Anchorandnegroandeffects: often - dry mouth, sweating, constipation, accommodation disorders, blurred vision, urination disorders; sometimes - tides, mydriasis; to the departmentьcases - glaucoma.

From the sense organs: paresis of accommodation, blurred vision (blurred vision), taste change, tinnitus.

From the digestive system: dry mouth, stomatitis, glossitis, dental caries, nausea, vomiting, diarrhea, changes in functional hepatic samples, hepatitis, jaundice, often - discomfort in the abdomen, constipation.

From the side of the cardiovascular system: sometimes - sinus tachycardia, palpitation, orthostatic hypotension, clinically insignificant change on the ECG (eg, interval ST or prong T) in patients not suffering from heart disease; rarely - arrhythmias, increased blood pressure; to the departmentьcases - violations of intracardiac conduction (eg, expansion of the QRS complex, changes in the interval PQ, blockade of the legs of the bundle.

On the part of the organs of hematopoiesis: Thrombocytopenia, thrombocytopenic purpura, rarely - agranulocytosis. Ochenь rarely - leukopenia, eosandnophilia.

From the endocrine system: hyperprolactinemia, hypertrophy breast cancer, galactorrhea, gynecomastia. Ochenь rarely - Syndrome of inadequate secretion of ADH.

From the genitourinary and urinary system: decreased potency, decreased libido, dysmenorrhea, urinary retention.

From the side of metabolism: increased appetite, decreased appetite, increase or decrease in body weight, sweating, swelling, hypo- and hyperglycemia.

Allergic reactions: itching, photosensitivity, "tides" of blood to the skin face, a feeling of heat or cold, hyperpyrexia.

Other: petechiae, alopecia.

With long-term treatment, especially in high doses, with a sharp stoptreatment, it is possible to develop a withdrawal syndrome: headache, nausea, vomiting, diarrhea, as well as irritability, sleep disturbance with bright, unusual dreams, increased excitability.

Overdose:

Symptoms and complaints that develop with an overdose of Clomipramine, taken inward, are similar to those described in the overdose of other tricyclic antidepressants. The main complications are violations of the heart and neurological disorders. In children, a random intake of the drug inside should be regarded as a very serious and fatal accident, regardless of the magnitude of the dose taken.

Complaints and Symptoms

Symptoms usually appear within 4 hours after taking the drug and reach the maximum expression after 24 hours.Due to delayed absorption (anticholinergic action of the drug), prolonged half-life and gepoententeric recirculation of the active substance, the period of time that the patient remains in the "risk zone" is 4-6 days.

The following complaints and symptom may be observeds:

From the central nervous system drowsiness, stupor, coma, ataxia, anxiety, agitation, increased reflexes, rigidity muscles, choreoathetoid movements, convulsions.

From the cardiovascular system: hypotension, tachycardia, arrhythmias, intracardiac conduction disorders, shock, heart failure; in very rare cases - cardiac arrest.

In addition, respiratory depression, cyanosis, vomiting, fever, mydriasis, sweating, oliguria, or anuria are possible.

Treatment

There is no specific antidote, the treatment is mainly symptomatic and supportive, When suspected of an overdose of Anafranil, especially in children, the patient should be hospitalized and closely monitor for at least 72 hours.

If the patient is conscious, promptly wash the stomach or induce vomiting.If the patient is unconscious, before starting the gastric lavage should be to intubate the trachea with a tube with a cuff to prevent aspiration; Vomiting in this case does not cause. These activities are recommended at tIn the event that 12 hours or more have passed since the overdose, since the anticholinergic action of Clomipramine may slow the emptying of the stomach. It is useful to use activated carbon to slow the absorption of the drug.

Treatment is based on the use of modern methods of intensive therapy with continuous monitoring of heart functions, gas composition and blood electrolytes, as well as the application, if necessary, of such urgent measures as anticonvulsant therapy, artificial ventilation and resuscitation methods. Since the reports appeared that physostigmine can cause a pronounced bradycardia, asystole and seizures, it is not recommended to use this drug to treat an overdose of Clomipramine. Hemodialysis and peritoneal dialysis are not effective, as Clomipramine concentrations in the blood plasma are low.

Interaction:

Inhibitors MAO: do not do it assign Clomipramine during, at least 2 weeks after the abolition of MAO inhibitors (there is risk development of of such heavy symptoms and conditions, such as hypertensive crisis, hyperpyrexia, myoclonus, generalized convulsions, delirium and coma). The same rule should be followed If the MAO inhibitor is administered after the previous treatment with clomipramine. In either of these cases, the initial dose Clomipramine or MAO inhibitors should be small, they should be increased gradually, under the constant control of the effects of the drug.

The existing experience shows that Clomipramine may be appointed earlier than 24 hours after the withdrawal of MAO-A inhibitors of reversibility, such as moclobemide. But, if such a drug is prescribedAfter the withdrawal of Clomipramine, the duration of the break should be at least 2 weeks.

Antandadrenergicandcheskie preparations: Influencing neuronal transmission of excitation. Clomipramine can reduce or completely eliminate the antihypertensive effects of guanethidine, betanidine, reserpine, clonidine and alphamethyldopa.Therefore, in those cases when simultaneouslywith the admission of Clomipramine requires the treatment of arterial hypertension, Other medications should be used (for example, diuretics, vasodilators or beta-adrenoidsblthe rotors).

TOlonedin intensifies the inhibitory effect on the central nervous system.

Increases the frequency and severity of expyramidal effects, medicinal means that can cause such reactions.

Clomipramine in admission with alpha-adrenostimulatorsand for intranasal administration or for use in ophthalmology (with significant systemic absorption) may enhance vasoconstrictor deffect the latter.

Atropine increases the risk of paralytic obstruction.

Sympathomimetic drugs: Clomipramine can enhance the effect on the cardiovascular system of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (even when these substances are included in the local anesthetics).

The drugs that oppress the central nervous system: tricyclic antidepressants may increase the effect of alcohol and other drugs that have a depressing effect effects on the central nervous system (eg, barbiturates, benzodiazepines or agents for anesthesia).When combined with holinoblokatorami, phenothiazines, benzodiazepines, sedative and central cholinoblocking effects are increased, the risk of epileptic seizures increases. Phenothiazines can increase the risk of neuroleptic malignant syndrome.

Anticonvulsant medications can enhance the depressing effect on the central nervous system, reduce the threshold of convulsive activity, and reduce the effectiveness of these drugs.

Anticholinergics: tricyclic antidepressants may strengthen the anticholinergic effect of a number of drugs (eg, phenothiazines, antiparkinsonics, atropine, biperiden, antihistamines) on the organ of vision, the central nervous system, the intestines and the bladder.

Quinidine: tricyclic antidepressants should not be prescribed in combination with antiarrhythmic agents such as quinidine.

Selective serotonin reuptake inhibitors: a joint application of TOLomipramine with these agents may lead to an increased effect on the serotonin system. In addition, fluoxetine fluvoxamine can increase the concentration of clomipramine in plasma blood, which is accompanied by the development of appropriate adverse reactions.

Medicines that activate the monooxidase enzyme system of the liver: drugs that activate the system (for example, barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives), can increase the metabolism of Clomipramine and reduce the concentration it is in the blood plasma, which leads to a decrease in its effectiveness. Can an increase in the concentration of phenytoin or carbamazepine in the blood plasma, which is accompanied by corresponding adverse reactionsand. If these medicinal combinations are used, it may be necessary revision doses preparations.

Neuroleptics: joint use of these funds can lead to to an increase in the level of tricyclic antidepressants in plasma torovi, lowering the threshold of convulsive readiness and developing seizures.

M-holinoblokatory and antipsychotic drugs increase the risk of hyperpyrexia (especially in hot weather).

Clomipramine decreases the effectiveness phenitonin and alfa-adrenoblockers.

Anticoagulants: tricyclic antidepressants can enhance the anticoagulant effect of coumarin derivatives due to inhibition of their metabolism in the liver. In such cases, the prothrombin time should be carefully monitored.

Qimetidine, methylphenidate, estrogens: these medicines lead to increase concentration of tricyclic antidepressants in blood plasma, therefore, when they are used, it is recommended to lower the dose antidepressantat.

Clomipramine may increase the depression caused by GCS.

Cocaine, pimozide, probucol increase the risk of cardiac arrhythmias that is manifested in elongation of the Q-T inte- gral on the ECG.

Joint reception with thyroid hormones causes mutual reinforcement of the therapeutic effectfect and toxic effects onthe last (including cardiac arrhythmias and a stimulating effect on the central nervous system). Combination with thioridazine can lead to severe arrhythmias.

Drugs for treatment of thyrotoxicosis increase the risk development of granulocytosis.

Co-administration with disulfiram and other inhibitors of acetal dehydrogenase provokes an airspace.

It is possible to increase hematotoxicity when co-administered Clomipramine with hematotoxic lmedicines.

Special instructions:

Treatment of elderly patients

Treatment with clomipramine in old age should be under careful control of liver and cardiovascular function and with the use of minimal doses of the drug, increasing them gradually, in order to avoid the development of delirious disorders, hypomania and other complications.

Clomipramine can reduce the threshold of convulsive activity, so one should consider the possibility of seizures in patients with those in the history, and in the category of patients who are predisposed to this because of age or trauma. During the period of treatment, peripheral blood control is necessary, because of the risk of developing agranulocytosis.

Patients with MD depressive phaseP can go into a manic stage.

Effect on the ability to drive transp. cf. and fur:Patients receiving Clomipramine, should be warned that they may have blurred vision, drowsiness and other abnormalities on the part of the central nervous system, and that in such cases they should refuse to drive a car, work with mechanisms, and also engage in other activities that require increased attention and quick reaction. Patients should also be warned that, that the use of alcohol or other drugs can enhance these phenomena.

Form release / dosage:

Film-coated tablets, 25 mg.

Packaging:

For 30 tablets in a plastic bottle with a lid. 1 bottle each together with the instructions for use are placed in a cardboard box.

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. 3 contour cell packs together with instructions for use in a cardboard box.

Storage conditions:In a dry, protected from light at a temperature of 15 to 25 ° C
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:P N 013295/01

Date of registration:28.02.2008 / 14.01.2013

Expiration Date:Unlimited

The owner of the registration certificate:Apothec Inc.Apothec Inc. Canada

Manufacturer: & nbsp

APOTEX, Inc. Canada

Representation: & nbspVECTOR-MEDICA CJSC VECTOR-MEDICA CJSC Russia

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clomipramine (Clomipramine)