Clofranil, tablets 25 mg 50 pcs

Clofranil is a tricyclic antidepressant from the group of non-selective inhibitors of neuronal takeover of monoamine. It has a pronounced thymoanaleptic effect, belongs to the antidepressants of balanced action (combination of psychostimulant and anxiolytic, sedative action). The mechanism of antidepressant action of clomipramine is related to its ability to inhibit reuptake of noradrenaline and serotonin by the corresponding neurons (serotonin reuptake is reduced to a greater extent than with other tricyclic antidepressants). With long-term use it reduces the functional activity of beta-adreno- and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems that are disturbed in depressed states.

It has a pronounced central and peripheral alpha-adrenoblocking, as well as M-cholinoblocking, H1-histamine-blocking action. It has a central analgesic, antibulemic effect, and is effective for nocturnal urinary incontinence. The psychostimulant effect is less pronounced than that of imipramine, and the sedative effect is weaker than that of amitriptyline. The antidepressant effect is already seen in 1 week of use.

Pharmacokinetics.

Absorption is fast, almost 100%, bioavailability is about 50% (effect of “first passage” through the liver). After a single oral administration of 50 mg of the drug, Cmax of clomipramine is reached within 4 hours, and of its desmethylated metabolite (which is a potent inhibitor of noradrenaline reuptake) – within 4-24 hours.

In patients receiving clomipramine at a dose of 25 mg three times daily, the plasma Csp is established 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 binding to plasma proteins is high – 97.6%.

The volume of distribution is 12-17 l/kg. Concentration in cerebrospinal fluid is 2% of that in blood plasma, in mother’s milk – similar to plasma. T1/2 is 21 hours. T1/2 may be prolonged to 36 hours in depressed patients. The kidneys excreted 2/3 as water-soluble compounds and about 1/3 – through the intestine. The amount of unchanged clomipramine and its active metabolite excreted by the kidneys is not more than 1% of the taken dose, the rest is excreted as hydroxylated metabolites.

Indications

Adults:

– treatment of depressive conditions of different etiology, proceeding with different symptomatology: endogenous, reactive, neurotic, organic, masked, involutionary forms of depression; depression in patients with schizophrenia and psychopathies: Depressive syndromes occurring in old age, due to chronic pain syndrome or chronic somatic 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 (OCS);

– nocturnal enuresis (only in patients over 5 years of age and if organic causes of the disorder are excluded).

Active ingredient

Clomipramine

Composition

1 coated tablet contains clomipramine hydrochloride 25 mg.

Associated substances:

Lactose,

Corn starch,

Microcrystalline cellulose, <

colloidal silica,

purified talc,

magnesium stearate,

brilliant blue,

sodium carboxymethyl starch,

titanium dioxide,

Hypromellose 2910 (Metocel E5),

MacroGol 6000,

Dye diamond blue.

How to take, the dosage

Appoint orally (during or after meals).

The doses are set individually. For depression, OCS, phobias, start with 75 mg (25 mg 2-3 times a day). During the first week, the dose is gradually increased to 150 mg/day (in severe depression, resistant to therapy, the dose is increased to 300 mg), divided into 2-3 doses. After marked improvement, the patient is transferred to a maintenance dose of 100 mg (25 mg 2-4 times a day).

In elderly patients, the initial daily dose is 10 to 12.5 mg (1/2 tablet); gradually, over 10 days, the dose is increased to 30-50 mg/day.

In cataplexy, concomitant narcolepsy, 25-75 mg/day. In chronic pain syndromes – orally, at a dose of 10-150 mg/day, taking into account the concomitant prescription of analgesics to the patient, as well as the possibility of reducing the administered dose of the latter. Panic attacks, agoraphobia: initial dose 10-12.5 mg per day. Then, depending on tolerance, the dose is increased until the desired effect is achieved. The daily dose may be from 25 mg to 100 mg. If necessary, the dose may be increased to 150 mg per day. It is recommended that treatment not be discontinued for at least 6 months, slowly reducing the maintenance dose of the drug during this time.

Children and adolescents. Obsessive-compulsive syndromes: the starting dose is 12.5 mg. During the first 2 weeks, the dose is gradually increased, taking into account tolerance, until the daily dose is either 100 mg. or calculated at 3 mg/kg – whichever is less. Over the next few weeks, the dose continues to be gradually increased until it reaches a daily dose of either 200 mg or calculated at 3 mg/kg, whichever is lower.

Nighttime 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 over 12 years, 25-75 mg. The use of higher doses is indicated for those patients who have no clinical effect after 1 week of treatment. Usually the whole daily dose of the drug is administered in one dose after dinner, but in cases when involuntary urination is observed in early night hours, a part of Clofranil dose is administered earlier – at 4 pm. After achieving the desired effect, treatment should be continued for 1-3 months, gradually reducing the dose of Clofranil.

Interaction

Klofranil increases CNS depressant effects of the following drugs: neuroleptics, sedatives and hypnotics, anticonvulsants, narcotic analgesics, general anesthetics, alcohol; it shows synergism in interaction with other antidepressants.

In co-administration of Clofranil with neuroleptics (phenothiazines), benzodiazepines, and/or anticholinergic drugs, febrile temperature reaction and paralytic ileus may occur.

Clofranil increases the hypertensive effects of catecholamines and other adrenostimulants, which increases the risk of cardiac rhythm disturbances, tachycardia, marked increase in blood pressure: but inhibits the effects of drugs affecting noradrenazine release.

Clofranil may decrease the antihypertensive effect of guanethidine and drugs with a similar mechanism of action, and also weaken the effect of anticonvulsants.

In concomitant use of Clofranil and anticoagulants – coumarin derivatives or Indandion – the anticoagulant activity of the latter may increase.

Concomitant use of Clofranil and cimetidine may increase the plasma concentration of clomipramine with possible development of toxic effects.

The inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin) decrease plasma concentrations of clomipramine.

Clofranil increases the effect of antiparkinsonian drugs and other drugs that cause extrapyramidal reactions.

Hinidine slows down 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 glucocorticosteroid-induced depression; coadministration with thyrotoxicosis medications increases the risk of agranulocytosis.

The simultaneous use of Clofranil with MAO inhibitors may be fatal. A break in treatment between MAO inhibitors and tricyclic antidepressants should be at least 14 days!

Special Instructions

Before therapy with Clofranil for nocturnal enuresis in children and adolescents is initiated, the balance of potential benefit and risk to the patient should be assessed. Consideration should be given to the possibility of alternative therapy.

The risk of suicidal behavior is inherent in depression and may persist until substantial remission is achieved. Clofranil may exacerbate anxiety disorders, especially at the beginning of therapy. Therefore, a combination with benzodiazepines or neuroleptics and constant medical supervision (entrusting trusted persons with the storage and dispensing of the drug) may be indicated at the beginning of treatment.

Clofranil may lower the seizure threshold, so the possibility of seizures in patients with a history of seizures, and in that category of patients who are predisposed to it because of age or trauma should be considered. During the treatment period it is necessary to control peripheral blood because of risk of agranulocytosis development, as well as blood pressure control.

The treatment with Clofranil in the elderly should be done under close monitoring of liver and cardiovascular function and, with the use of minimal doses of the drug, increasing them gradually to avoid the development of delirium disorder, hypomania and other complications.

Patients with a depressive phase may progress to a manic phase.

Before general or local anesthesia, the anesthesiologist should be warned that the patient is taking Clofranil.

Alcohol should not be taken while taking Clofranil.

Impact on driving and operating machinery

Driving, operating machinery and other types of work requiring increased concentration, and taking alcohol are prohibited while taking Clofranil.

Contraindications

– hypersensitivity to clomipramine or any other ingredients of the drug, cross-sensitivity to tricyclic antidepressants from the dibenzazepine group;

– concurrent use of monoamine oxidase inhibitors (MAOIs), as well as less than 14 days before and after their use. Concomitant use of selective MAO-A reversible inhibitors, such as moclobemide, is also contraindicated;

– recently suffered myocardial infarction;

– congenital QT-interval prolongation syndrome;

– pregnancy, breastfeeding;

– children under 5 years of age.

With caution: convulsive syndrome (including in anamnesis), schizophrenia (aggravation of productive symptoms is possible), organic brain diseases, elderly age, concurrent use of neuroleptics, chronic alcoholism, psychoactive substance abuse, cardiovascular diseases (chronic heart failure, atrial conduction disorders, including AV block of degree I-III, arrhythmia), intraocular hypertension, closed-angle glaucoma, urinary retention, severe liver diseases, tumors of adrenal medulla (including pheochromocytoma, neuroblastoma), hyperthyroidism or concomitant use of thyroid hormone products, chronic constipation, suppression of medullary hematopoiesis.

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Side effects

Nervous system disorders: Headache, dizziness, asthenia, somnolence or insomnia, fear, anxiety, psychomotor agitation, aggressiveness, paresthesias, fine tremor, hypertonicity of muscles, speech impairment, ataxia, hallucinations, confusion, disorientation, depersonalization, decreased concentration, delirium, patients in the depressive phase may develop manic disorders, “nightmare” dreams, less frequently – seizures, myoclonias. Extrapyramidal disorders, agitation.

Sense organs: accommodation paresis, blurred vision (shroud before eyes), change in taste, tinnitus.

Digestive system disorders: dry mouth. anorexia. nausea, vomiting, diarrhea, changes in functional liver function tests, hepatitis, jaundice, constipation, increased appetite.

Cardiovascular system: orthostatic hypotension, sinus tachycardia, ECG changes, very rarely – intracardiac conduction disorders, including dilation of QRS complex, prolongation of QRS time. dilated QRS complex, prolongation of Q-T interval, change of P-Q interval, Gis pedicle block, ventricular tachycardia (torsades-depoints type), especially against the background of hypokalemia, increased arterial pressure.

Hematopoietic organs: very rarely leukopenia, agranulocytosis, eosinophilia, thrombocytopenia, purpura.

Endocrine system disorders: very frequently – weight gain, libido and potency disorders, dysmenorrhea; frequently – galactorrhea, enlarged mammary glands; very rarely – syndrome of inadequate secretion of ADH.

Urinary system disorders: urinary retention.

Allergic reactions: itching, photosensitization, “rushes” of blood to the face, feeling of heat or cold, hyperpyrexia.

Others: petechiae, alopecia, increased incidence of dental caries. With long-term treatment, especially in high doses, if treatment is stopped abruptly, withdrawal syndrome may develop: headache, abdominal pain, nausea, vomiting, diarrhea, as well as irritability, sleep disorders with vivid, unusual dreams, increased excitability.

Overdose

Symptoms: somnolence, stupor, coma, ataxia, insomnia, agitation, hyperreflexia, muscle rigidity, choreoathetosis, seizures, BP decrease, tachycardia, arrhythmias, intraventricular blockade, AV blockade, cardiac insufficiency, cyanosis, body temperature increase, mydriasis, oliguria, anuria, respiratory center depression, respiratory arrest. Symptoms develop 4 hours after overdose, reach their maximum after 24 hours and last for 4-6 days.

Treatment: gastric lavage, symptomatic treatment. Injection of physostigmine is contraindicated because of increased risk of seizures. Hemodialysis is not effective. Cardiovascular monitoring (ECG) for 5 days is indicated, as relapse may occur after 48 hours or later. Hemodialysis and forced diuresis are ineffective.

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Pregnancy use

It is contraindicated in pregnancy, during breastfeeding.

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