KLOFRANIL

Active material: Clomipramine
When ATH: N06AA04
CCF: Antidepressant
When CSF: 02.02.01
Manufacturer: Sun Pharmaceutical Industries Ltd. (India)

Pharmaceutical form, composition and packaging

Pills, covered shell blue, round, with dividing risk on the one hand.

Excipients: lactose, starch, microcrystalline cellulose, colloidal silicon dioxide, sodium methylparaben, talc, magnesium stearate, Diamond blue, sodium starch glycolate, polyethylene glycol, Eudrahit E100, sodium lauryl.

10 PC. – packings Valium planimetric (5) – packs cardboard.

DESCRIPTION OF ACTIVE SUBSTANCES

Pharmacological action

Antidepressant from a group of tricyclic compounds. The effect of the drug is associated with the stimulation of adrenergic and serotonergic mechanisms in the central nervous system due to the oppression of the reverse neuronal seizure of mediators. More affects the capture of serotonin; This, apparently, its effectiveness is due to the treatment of intrusive and compulsive disorders. The antidepressant effect occurs relatively quickly (at the first week of treatment). It has adrenal -locking (Mostly alpha₁), holin -locking and antihistamine activity.

The psychostimulating effect of clomipromin is less expressed, than Imipramin, A sedative effect – weaker, than amitriptylin.

Pharmacokinetics

After administration orally or in/m, the introduction is absorbed quickly and completely. C_max plasma achieved through 1.5-4 hours after ingestion. Plasma protein binding – 97.6%. V_d – 12 l. Subjected to intensive metabolism with the formation of an active metabolite of desmethyllomipramine.

T_1/2 in the final phase of 21 no. Displayed with urine in the form of metabolites and unchanged substance, through the intestine – as metabolites.

Testimony

Depressive states of various etiologies (incl. Endogenous, reactive, neurotic, Organic, masked and involutionary depression); Depressive syndrome for schizophrenia and personality disorders; Preight and Senile Depression; Depressive states with prolonged pain syndrome and chronic somatic diseases; Depressive reactive disorders, neurotic and psychopathic nature, including their somatic equivalents in children; obsessive-compulsive syndromes (phobia), Panic attacks of fear, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic diseases, atypical facial pain, postgerpeticheskaya neuralgia, Posttraumatic neuropathy, Diabetic or others. perifericheskaya neuropathy), Narcolepsy, accompanied by a cataplexion; headache; prevention of migraine

Dosage regimen

Inside adults – by 25-50 mg 2-3 times / day; children depending on age – 25-50 mg / day. Adults in/m 25-100 mg / day, / drip 50-75 mg 1 time / day.

The maximum dose: When administering inside adults is outpatient – 250 mg / day, in hospital – 300 mg / day; older children 10 years – 3 mg / kg / day, but not more 200 mg / day.

Side effect

CNS: often – dizziness, fatigue, tremor, headache, myoclonus, visual impairment; rarely – dysgeusia, feeling the heat, midriaz, disorientation, hallucinations (most likely in elderly patients and in Parkinson's disease), anxiety state, ažitaciâ, sleep disorders, craze, hypomania, aggressiveness, memory impairment, depersonalization, zevota, nightmares, increased depression, impaired concentration, delirium, speech disorders, paresthesia, Muscular tone disorders, noise in ears, convulsions, ataxia; in some cases – Strengthening psychotic symptoms, glaucoma.

Cardio-vascular system: rarely – postural hypotension, sinus tachycardia, ECG changes, palpitation, Arrhythmia, increased blood pressure; in some cases – EEG changes, cardiac conduction disorders.

From the digestive system: often – nausea, dry mouth, constipation; rarely – vomiting, abdominal discomfort, diarrhea, anorexia, increase in transaminases; in some cases – hepatitis, jaundice.

From the hematopoietic system: in some cases – leukopenia, agranulocytosis, thrombocytopenia, eozinofilija, trombotsitopenicheskaya purpura.

Metabolism: often – increased appetite, weight gain.

On the part of the endocrine system: often – disorders of libido and potency, galactorrhea, An increase in the pectoral glands; in some cases – syndrome of inappropriate secretion of ADH, swelling.

Dermatological reactions: rarely – photosensitivity.

Allergic reactions: rarely – skin rash, itch.

Other: often – increased sweating; in some cases – fever.

Contraindications

Recent myocardial infarction, Blockade of the conductive myocardial system, Arrhythmia, craze, severe liver failure, zakrыtougolynaya glaucoma, urinary retention, I trimester of pregnancy, lactation, Increased sensitivity to clomipramine and other tricyclic antidepressants from the group of dibenzoazepine derivatives.

Pregnancy and lactation

Contraindicated for use in the I trimester of pregnancy. Do not use in the 2nd and 3rd trimesters of pregnancy, except in cases of emergency. Adequate and well -controlled studies of the safety of the use of clomipromin during pregnancy in humans were not carried out.

Klomipramine in a small amount is released with breast milk, Therefore, if it is necessary to apply the issue of stopping breastfeeding during lactation..

Cautions

Caution is used in patients with a reduced convulsive threshold; In severe liver diseases or kidneys; during treatment with steroid hormones; with pheochromocytoma and neuroblastoma due to the risk of developing hypertensive crisis; in hyperthyroidism; diabetes (Correction of the dosing of hypoglycemic drugs is required).

Before starting treatment, blood pressure control is necessary, During the treatment period, it is recommended to control the picture of peripheral blood, long-term therapy – Control of the functions of the heart and liver.

Clomipramine can be used no earlier than through 14 days after discontinuation of MAO inhibitors, Starting therapy with a minimum dose. Should not be used simultaneously with sympathomy, incl. with epinephrine, ephedrine, isoprenalin, norepinephrine, phenylephrine, fenilpropanolaminom; with quinidine -like antiarrhythmic drugs. With the simultaneous use of clomipromin with alprazolam or disulfiram, a reduction in the dose of clomipromin is required.

Patients with a tendency to suicide in the initial period of treatment need constant medical control.

The use of electric shock against the background of the use of clomipramine is possible only according to strict indications and with a careful observation of a doctor.

With a sudden cessation of treatment, it is possible to develop cancellation syndrome.

During treatment, avoid alcohol.

It is not recommended for oral administration to children to the age of 6 years, parenterally – Children up to 12 years.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment should refrain from potentially hazardous activities, requiring attention and quick emotional reactions.

Drug Interactions

In an application with drugs, have a depressing effect on the central nervous system, possibly significant strengthening of oppressive action on the central nervous system, gipotenzivnogo actions, respiratory depression.

If you are applying with tools, having anticholinergic activity, it is possible to strengthen anticholinergic action.

With the simultaneous use of clomipromin, it can reduce or completely eliminate the antihypertensive effect of anti -adreno., affecting the neuronal transmission of excitation (guanethidine, ʙetanidina, reserpine, clonidine and alpha-methyldopa).

While the use of antipsychotics (neuroleptics) it is possible to increase the level of bloodupomine in blood plasma, reduction of the threshold of convulsive readiness and the development of seizures. Combination with thyoridazin can lead to severe arrhythmias.

It is possible to reduce the concentration of clomipromin in blood plasma due to the induction of microsomal liver enzymes under the influence of barbiturates.

Together with the use of MAO inhibitors are possible hypertonic Kriz, hyperpyrexia, myoclonus, generalized seizures, delirium and coma.

With the simultaneous use of selective inhibitors of the reverse capture of serotonin (incl. Fluoxetine and Fluoxamine) it is possible to strengthen the action on the serotonin system. Fluoxetine and fluvkamin can increase the concentration of bloodupomine in blood plasma, which is accompanied by the development of appropriate side effects.

Klomipramine can enhance the effect on the cardiovascular system of adreno- and sympathomimetic agents (epinephrine, norepinephrine, isoprenaline, Ephedrine and phenylefrin), including, When these substances are included in a combination with local anesthetics.

With simultaneous use with ademetionine, the case of the development of serotonin syndrome is described; with sodium valproate – The case of increasing the concentration in the blood plasma of clomipromin and its metabolite is the desecrathyllomiprammin plasma.

There is a message about increasing the concentration in the blood plasma of clomipramine and its main metabolite (Desmethyllomipramine) With simultaneous use with carbamazepine.

With simultaneous use with paroxetin, the concentration of the bloodpramine of its metabolite S-dezethyllomipramine in the blood plasma of the blood, apparently, In connection with the inhibiting of the isoenzyme CYP2D6 .

With simultaneous use with cimetidin, it is possible to increase the concentration of clomipromin in blood plasma due to the inhibiting of microsomal liver enzymes under the influence of cimetidine.

The case of increasing the concentration of clomipromin in blood plasma is described, What is due to the inhibiting of cyp3a3/4 isoenzymes under the influence of erythromycin.

With simultaneous use with estrogens, a violation of the metabolism of clomipromin is possible.

It is possible to strengthen ethanol, especially during the first few days of therapy with clomipramine.