Composition, form of production and packaging
The tablets covered with a cover of blue color, round, with delicate risk on one side.
clomipramine hydrochloride 25 mg
Auxiliary substances: lactose, corn starch, microcrystalline cellulose, colloidal silicon dioxide, talcum purified, magnesium stearate, brilliant blue, sodium carboxymethyl starch, titanium dioxide, hypromellose 2910 (metocel E5), macrogol 6000, brilliant blue dye.
10 pieces. - Strips aluminum (5) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Clofranil is a tricyclic antidepressant from a group of non-selective inhibitors of neuronal capture of monoamines. Has a pronounced timoanaleptic effect, refers to antidepressants of balanced action (a combination of psychostimulating and anxiolytic, sedative action). The mechanism of antidepressant action of clomipramine is associated with the ability to inhibit the reuptake of norepinephrine and serotonin by the corresponding neurons (the reverse capture of serotonin decreases more than in the case of other tricyclic antidepressants). With prolonged use reduces the functional activity of beta-adrenergic and serotonin receptors of the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems, disturbed in depressive states.
Has a pronounced central and peripheral alpha-adrenoblocker, as well as M-cholinoblocking, H1-histamine-blocking action. Has a central analgesic, anti-bulimic action, is effective in bedwetting. The psychostimulatory effect is less pronounced than that of imipramine, and the sedative effect is weaker than that of amitriptyline.Antidepressant effect is manifested as early as 1 week of use.
Absorption - fast, almost 100%, bioavailability - about 50% (the effect of "first passage" through the liver). After a single oral administration, 50 mg of the drug C maxclomipramine is reached in 4 hours, and its desmethylated metabolite (which is a potent inhibitor of noradrenatin reuptake) - for 4-24 hours. In patients treated with clomipramine 25 mg 3 times a day, Css in plasma is formed 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 a day in the evening, respectively, 70 and 81 ng / ml. The connection with plasma proteins is high - 97.6%.The volume of distribution is 12-17 l / kg. Concentration in the cerebrospinal fluid - 2% of that in the blood plasma, in the mother's milk - is similar to plasma. T 1/2 - 21 hours. In patients with depression, the elongation of T 1/2 up to 36 hours is possible. The kidneys are taken out 2/3 in the form of water-soluble compounds and 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.
- treatment of depressive conditions of various etiologies, taking place with various symptoms: endogenous, reactive, neurotic, organic, masked, involutional forms of depression; depression in patients with schizophrenia and psychopathies: depressive syndromes arising in old age due to chronic pain syndrome or chronic physical diseases; Depressive mood disorders of reactive, neurotic or psychopathic nature;
- obsessive-compulsive syndromes;
- chronic pain syndrome;
- phobias and panic attacks;
cataplexy accompanying narcolepsy.
Children and adolescents:
- obsessive-compulsive syndrome (ACS);
- nocturnal enuresis (only in patients over the age of 5 years and with the exception of organic causes of the disease).
Assign inside (during or after eating).
Doses are set individually. With depression, ACS, phobias begin with 75 mg (25 mg 2-3 times / day). During the first week, the dose is gradually increased to 150 mg / day (with severe depression resistant to therapy, the dose is increased to 300 mg), divided into 2-3 doses. After a marked improvement, the patient is transferred to a maintenance dose of 100 mg (25 mg 2-4 times / day).
In elderly patients, the initial daily dose is 10 - 12.5 mg (1/2 tablet); gradually, within 10 days, the dose is increased to 30-50 mg / day.
With cataplexy, concomitant narcolepsy - 25-75 mg / day. In chronic pain syndromes - inside, at a dose of 10-150 mg / day, taking into account the concomitant use of the patient with analgesics, as well as the possibility of reducing the administered dose of the latter. Panic attacks, agoraphobia: an initial dose of 10-12.5 mg per day.Then, depending on the tolerance, the dose is increased to achieve the desired effect. The daily dose can be from 25 mg to 100 mg. If necessary, it is possible to increase the dose to 150 mg per day. It is recommended not to discontinue treatment for at least 6 months, slowly reducing during this time a maintenance dose of the drug.
Children and teenagers. Obsessive-compulsive syndromes: the initial dose is 12.5 mg. During the first 2 weeks, the dose is gradually increased, taking into account tolerability, to a daily dose of either 100 mg. or calculated from the calculation of 3 mg / kg - depending on which dose is less. Over the next few weeks, the dose is gradually increased to a daily dose of either 200 mg or calculated at 3 mg / kg, whichever is lower .
Nocturnal enuresis: the initial daily dose of Anafranil for children aged 5-8 years is 20-30 mg; for children aged 9-12 years - 25-50 mg; for children older than 12 years - 25-75 mg. The use of higher doses is indicated for those patients who have completely 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 Clofranil is prescribed earlier - at 16 hours. After achieving the desired effect, treatment should be continued for 1-3 months, gradually reducing the dose of Clofranil.
From the side of the nervous system: headache, dizziness, asthenia, drowsiness or insomnia, fear, anxiety, psychomotor agitation, aggressiveness, paresthesia, small tremor, hypertonic muscle, speech disturbance, ataxia, hallucinations, confusion, disorientation, depersonalization, , delirium, in patients in the depressive phase may develop manic disorders, "nightmarish" dreams, less often - convulsive seizures, myoclonia. extrapyramidal disorders, agitation.
From the sense organs: paresis of accommodation, blurred vision (veil before the eyes), taste change, tinnitus.
From the digestive system: dryness in the mouth. anorexia. nausea, vomiting, diarrhea, changes in functional hepatic samples, hepatitis, jaundice, constipation, increased appetite.
From the cardiovascular system: orthostatic hypotension, sinus tachycardia, changes on the ECG, very rarely - violation of intracardiac conduction, incl. expansion of the QRS complex, extension of the QT interval, change of the PQ interval. blockade of the bundle legs, ventricular tachycardia (such as "torsadesdepoints"), especially against hypokalemia, increased blood pressure.
On the part of the organs of hematopoiesis : very rarely - leukopenia, agranulocytosis, eosinophilia, thrombocytopenia, purpura.
On the part of the endocrine system: very often - weight gain, violation of libido and potency, dysmenorrhea; often - galactorrhea, enlarged mammary glands; very rarely - the syndrome of inadequate secretion of ADH.
From the urinary system: urinary retention.
Allergic reactions: itching, photosensitivity, "tides" of blood to the skin of the face, sensation of heat or cold, hyperpyrexia.
Other: petechiae, alopecia, increased incidence of dental caries. With prolonged treatment, especially in high doses, with a sudden cessation of treatment, the development of withdrawal syndrome is possible: headache, abdominal pain, nausea, vomiting, diarrhea, as well as irritability, sleep disturbance with bright, unusual dreams, increased excitability.
- Hypersensitivity to clomipramine or any other ingredients of the drug, cross-sensitivity to tricyclic antidepressants from the dibenzazepine group;
- simultaneous use of monoamine oxidase inhibitors (MAO), and also a period of less than 14 days before and after their use. The simultaneous use of selective MAO-A inhibitors of reversible action, such as moclobemide, is also contraindicated;
- recently transferred myocardial infarction;
- congenital lengthening syndrome of QT-interval;
- pregnancy, the period of breastfeeding;
- Children under 5 years.
With caution: convulsive syndrome (including in the anamnesis), schizophrenia (possibly exacerbation of productive symptoms), organic brain diseases, advanced age, simultaneous administration of neuroleptics, hr. alcoholism, substance abuse, cardiovascular diseases (chronic heart failure, intracardiac conduction disorders, including AV blockade of the I-III st., arrhythmia), intraocular hypertension, angle-closure glaucoma, urinary retention, severe liver disease, brain tumors adrenal glands (including pheochromocytoma, neuroblastoma), hyperthyroidism or simultaneous administration of thyroid hormone drugs, chronic constipation, suppression of bone marrow hematopoiesis.
PREGNANCY AND LACTATION
Contraindicated in pregnancy, during breastfeeding.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: severe liver disease.
APPLICATION FOR CHILDREN
Contraindicated in children under 5 years. Use in children older than 5 years is possible according to the dosing regimen.
APPLICATION IN ELDERLY PATIENTS
With caution: the elderly.
Prior to the initiation of Clofranil therapy for nocturnal enuresis in children and adolescents, the relationship between potential benefit and risk to the patient should be assessed. Consider the possibility of an alternative therapy.
Depression is characterized by the risk of suicidal actions, which can persist until a significant remission is achieved. Clofranil may increase anxiety disorders, especially at the onset of therapy. In this regard, at the beginning of treatment, a combination with benzodiazepines or antipsychotics and permanent medical supervision (entrusting proxies with storage and dispensing of the drug) can be indicated.
Clofranil may reduce the threshold of seizure activity, therefore, one should consider the possibility of seizures in patients with those with a 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, as well as control of blood pressure.
Treatment with clofranil in old age should be under careful control of the liver and cardiovascular system and, with the use of minimal doses of the drug, increasing them gradually, to avoid the development of delirious disorders, hypomania and other complications.
Patients with a depressive phase can go into a manic stage.
Before conducting general or local anesthesia, an anesthetist should be warned that the patient is taking Clofranil.
During the reception of Clofranil, alcohol is not allowed.
Impact on the ability to drive vehicles and manage mechanisms
During the reception of Clofranil it is prohibited to drive vehicles, service mechanisms and other types of work that require increased concentration of attention, as well as alcohol intake.
Symptoms: drowsiness, stupor, coma, ataxia, insomnia, agitation, hyperreflexia, muscle rigidity, choreoathetosis, convulsions, lowering blood pressure, tachycardia, arrhythmias, intraventricular blockade, AV blockade, heart failure, cyanosis, fever, mydriasis, oliguria, anuria, depression of the respiratory center, respiratory arrest.Symptoms develop 4 hours after an overdose, peak at 24 hours and last 4-6 days.
Treatment: gastric lavage, symptomatic treatment. The introduction of physostigmine is contraindicated because of the increased risk of seizures. Hemodialysis is not effective. Monitoring of cardiovascular activity (ECG) for 5 days is shown, since relapse can occur after 48 hours and later. Hemodialysis and forced diuresis are ineffective.
Clofranil strengthens the depressing effect on the CNS of the following drugs: neuroleptics, sedatives and hypnotics, anticonvulsants, narcotic analgesics. means for general anesthesia, alcohol; shows synergism when interacting with other antidepressants.
With the combined use of clofranil with neuroleptics (phenothiazines), benzodiazepines, and / or anticholinergic drugs, a febrile temperature reaction may occur, paralytic intestinal obstruction.
Clofranil enhances the hypertensive effects of catecholamines and other adrenostimulants, which increases the risk of heart rhythm disturbances, tachycardia, marked increase in blood pressure: but it inhibits the effects of drugs acting on the release of noradrenazine.
Clofranil may reduce the antihypertensive effect of guanethidine and drugs with a similar mechanism of action, and also weaken the effect of anticonvulsants.
With the simultaneous use of clofranil and anticoagulants - derivatives of coumarin or Indanedione - an increase in anticoagulant activity of the latter is possible.
With the simultaneous administration of clofranil and cimetidine, an increase in the concentration in the plasma of clomipramine is possible with the possible development of toxic effects.
Inductors of microsomatic liver enzymes (barbiturates, carbamazepine, phenytoin) reduce plasma concentrations of clomipramine.
Clofranil enhances the action of antiparkinsonian agents and other drugs that cause extrapyramidal reactions.
Quinidine slows the metabolism of Clofranil. Methylphenidate increases plasma concentrations of clomipramine.
The combined use of clofranil with disulfiram and other acetaldehyde dehydrogenase inhibitors may provoke delirium.
Estrogen-containing oral contraceptives may increase the bioavailability of clofranil; pimozide and probucol may increase cardiac arrhythmias. Clofranil may increase depression caused by glucocorticosteroids; joint use with drugs to treat thyrotoxicosis increases the risk of agranulocytosis.
Simultaneous administration of clofranil with MAO inhibitors can lead to death . A break in treatment between taking MAO inhibitors and tricyclic antidepressants should be at least 14 days!
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
List B. In a dry, protected from light, out of reach of children, at a temperature of not more than +30 C.
Shelf life - 4 years. Do not use after the expiration date stated on the package.