2010/09/20

Anafranil

Composition, structure and packing

Solution for in / and / m the introduction of transparent, colorless.

1 ml. clomipramine hydrochloride 12.5 mg.

1 amp. clomipramine hydrochloride 25 mg.

Other ingredients: glycerol, water, d / and.

Clinico-pharmacological group: Antidepressants.

Pharmacological action

Antidepressant drug (tricyclic antidepressant). Also has some analgesic (of central genesis), H2-gistaminoblokiruyuschee and antiserotoninovoe action helps eliminate bed-wetting and reduces appetite. It has a strong peripheral and central anticholinergic effects associated with high affinity for m-cholinergic receptors, a strong sedative effect connected with affinity for the H1-histamine receptors, and alpha-adrenoceptor blocking action. Has the properties of anti-arrhythmic drugs subgroups Ia, like quinidine in therapeutic doses, slows ventricular conduction (in overdose can cause severe intraventricular block).

The mechanism of antidepressant action is associated with an increase in the concentration of noradrenaline in the synapses and / or serotonin in the CNS. The accumulation of these neurotransmitters is the result of inhibition of reuptake of presynaptic membranes of neurons (reuptake of serotonin is reduced to a greater extent than on the background of other tricyclic antidepressants).

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 are impaired in depressive states. Eliminates psychomotor retardation, depressed mood, anxiety. Has analgesic action, which is believed to be associated with changes in concentrations of monoamines in the CNS, especially serotonin, and the impact on the endogenous opioid system.

The mechanism of anxiolytic action associated with a decrease in the rate of excitation of locus ceruleus by regulating the functions of alpha2-and beta-adrenergic receptors and norepinephrine turnover.

The mechanism of action for bulimia nervosa is unclear (perhaps similar to those with depression). Revealed a distinct effect of the drug in patients with bulimia as without depression, and if available, to the reduction of bulimia may occur without a concomitant weakening of the most depressed.

Antidepressant effect is already at 1 week of application.

Psychostimulant action is expressed to a lesser extent than imipramine, and sedative - weaker than amitriptyline. In attacks narcoleptic sleepiness effect is weak or absent.

Statement
depressive states of various etiologies and with various symptoms (endogenous, reactive, neurotic, organic, masked and involutional depression);
depressive symptoms in schizophrenia and personality disorders;
presenile and senile depression;
depression during long-term pain syndrome and chronic somatic diseases;
reactive depressive disorders, neurotic and psychopathic nature, including their somatic equivalents in children;
obsessive-compulsive syndromes (phobia), panic panic attacks, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic diseases, atypical facial pain, postherpetic neuralgia, posttraumatic neuropathy, diabetic or other peripheral neuropathy), the narcolepsy is accompanied by catalepsy;
headache, migraine (prevention).

Dosage regimen

Inside, during or immediately after a meal (to reduce the irritation of the gastric mucosa) in / m in / in. If possible, seek the appointment of the drug as possible at lower doses, especially in the treatment of elderly patients and adolescents with depression.

Depression, obsessive-compulsive syndromes and phobias - inside, and 25 mg 2-3 times daily or 1 tablet of long-acting (75 mg) 1 times a day, preferably in the evening. Within 1 week of treatment the daily dose gradually increased to 100-150 mg (2 tablets retard 75 mg).

If necessary, you can assign and large doses.

After reaching effect in the prescribed maintenance dose on average 50-100 mg or 1 tablet 75 mg. V / m: initial dose - 25-50 mg, then every day should be administered at 25 mg more, until the dose reaches 100-150 mg / day.

After improving gradually reduce the number of injections, and then transferred to oral maintenance dose.

In / in the introduction begin with a single drop infusion during 1.5-3 h 50-75 mg (contents of dissolved and thoroughly mixed with 250-500 ml 0.9% NaCl solution or 5% dextrose).

Given the daily fluctuations of the state of depressive patients, it is preferable to infusion in the morning. Outpatients after i / v infusion should be under strict supervision.

After achieving a noticeable effect (usually within the first 7 days) infusion continued for a further 3-5 days.

To maintain the achieved effect is necessary to continue ingestion. The gradual transition from / v injections to receive the inside can be facilitated by resorting to the intermediate phase in / m injection. In narcolepsy, accompanied by catalepsy, - inside, at a dose of 25-75 mg / day.

In chronic pain syndromes - inside, at a dose of 10-150 mg / day, given the concurrent appointment of a patient analgesics, as well as the possibility of reducing the injected dose of the latter.

Panic attacks: an initial dose - 10 mg / day, possibly in combination with benzodiazepines. Depending on the tolerability of the drug dose is increased to obtain the desired result, gradually stop taking the benzodiazepine. Do not discontinue treatment earlier than 6 months. During this time, should gradually reduce the dose supportive.

Geriatrics: an initial dose - 10 mg / day. Gradually (over 10 days) dose increased to the optimum (30-50 mg / day) and stick to this dose until the end of treatment.

Pediatrics: initial dose - 10 mg per day, within 10 days of daily dose increased: in children aged 5-7 years - up to 20 mg, aged 8-14 years - up to 20-50 mg, and children over 14 years - to 50 mg and above.

Side effect

Anticholinergic effects: blurred vision ("a veil before the eyes), paresis of accommodation, mydriasis, increased intraocular pressure (only in the eyes of the local anatomic predisposition - a narrow angle of anterior chamber), tachycardia, dry mouth, confusion, delirium or hallucination, constipation, paralytic ileus, difficulty urinating, reduced sweating.

Of the nervous system: drowsiness, asthenia, anxiety, disorientation, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, agitation, restlessness, manic state, hypomanic state, aggression, memory impairment, depersonalization, increased depression , reduced ability to concentrate, insomnia, nightmares, dreams, yawning, fatigue, activation of the symptoms of psychosis, headache, myoclonus, dysarthria, tremor of small muscles, especially the hands, arms, head and tongue, peripheral neuropathy (paresthesias), myasthenia gravis , myoclonus, ataxia, extrapyramidal syndrome, increased seizures, EEG changes, hyperpyrexia.

From the CCC: sinus tachycardia, palpitations, dizziness, orthostatic hypotension, collapse, clinically insignificant ECG changes (ST interval and T wave) in patients not suffering from heart disease, arrhythmia, blood pressure lability (decreased or increased blood pressure), violation of intraventricular conduction (expansion of the complex QRS, change the interval PQ, bundle branch block feet, AV block).

On the part of the digestive system: nausea, rarely - hepatitis (including a change in the functional "liver" tests and cholestatic jaundice), indigestion, vomiting, stomachalgia, increased appetite and body weight, or decreased appetite and weight loss, stomatitis, glossitis, dental caries, a change of taste , diarrhea, darkening of the tongue.

On the part of the endocrine system: an increase in size (swelling) of testicles, gynecomastia, enlargement of the mammary glands, hyperprolactinemia, galactorrhea, decreased or increased libido, reduced potency, hypo-or hyperglycemia, hyponatremia (decreased production of vasopressin), a syndrome of inappropriate secretion of ADH.

From the side of hematopoiesis: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia. Allergic reactions: skin rash, itching, rash, photosensitivity, angioedema.

Other: hair loss, tinnitus, edema, petechiae, "tides" of blood to the skin of the face, sensation of heat or cold, urinary retention, frequent urination, hypoproteinemia, hyperpyrexia. Symptoms of the syndrome of "cancellation" (after the sudden cancellation of long-term treatment): nausea, vomiting, diarrhea, headache, malaise, sleep disturbances, unusual dreams, unusual excitement, with the gradual abolition after long-term care - irritability, restlessness, sleep disturbances, unusual dreams.

Local reaction to / in the introduction: thrombophlebitis, lymphangitis, burning sensation, allergic skin reactions.

Overdose.

Symptoms: developed 4 hours after the overdose, reach a maximum after 24 h and lasts 4-6 days. If you suspect an overdose, especially in children, the patient should be hospitalized.

From the CNS: drowsiness, stupor, coma, ataxia, insomnia, hallucinations, anxiety, psychomotor agitation, reduced ability to concentrate, confusion, hyperreflexia, muscular rigidity, choreoathetosis, seizures.

From the CCC: lowering blood pressure, tachycardia, arrhythmia, a violation of intracardiac conduction (intraventricular block, AV block), characteristic of tricyclic antidepressants intoxication, ECG changes (especially the QRS), shock, CH, in very rare cases - cardiac arrest.

Other: respiratory depression, apnea, cyanosis, apnea, vomiting, hyperthermia, mydriasis, increased sweating, oliguria or anuria.

Treatment: oral uptake - gastric lavage, the appointment of activated charcoal, symptomatic and supportive therapy, in severe anticholinergic effects (lowering of blood pressure, arrhythmias, coma, myoclonic epileptic seizures) - the introduction of cholinesterase inhibitors (application Physostigmine is not recommended because of the increased risk of convulsions ) maintenance of blood pressure and water and electrolyte balance. Showing the control functions of SSA (including ECG) within 5 days (relapse can occur after 48 h and later), anticonvulsant therapy, mechanical ventilation and other resuscitation. Hemodialysis and forced diuresis are ineffective.

Contraindications
hypersensitivity
used in conjunction with MAO inhibitors and for 2 weeks before treatment,
myocardial infarction (acute and subacute periods)
acute alcohol intoxication,
acute intoxication with hypnotics,
analgesic and psychoactive drugs,
-closure glaucoma,
severe conduction disturbances (bundle branch block feet, AV block II Art.)
lactation,
children's age (10 years - for obsessive states, up to 12 years - with depression).

C carefully. Chronic alcoholism, asthma, manic-depressive psychosis, depression of bone marrow hemopoiesis, pregnancy (especially the I term), diseases of the CAS (angina, arrhythmias, heart block, CHF, myocardial infarction, hypertension), stroke, gastrointestinal disturbances in motor function (the risk of paralytic ileus), intraocular hypertension, liver and / or renal failure, hyperthyroidism, prostatic hyperplasia, urinary retention, schizophrenia (possible activation of psychosis), epilepsy, old age.

Pregnancy and lactation

Drugs are taken with caution.

Cautions

Before treatment is necessary to monitor blood pressure (in patients with low or labile blood pressure, it can be reduced even more) during treatment - control peripheral blood (in some cases may develop agranulocytosis, and therefore it is recommended to monitor blood picture, especially when increase in body temperature, the development of influenza-like symptoms and sore throat), with long-term therapy - control functions of the SSA and the liver.

In elderly and patients with diseases of the SSA shows control of heart rate, blood pressure, ECG. The ECG may appear clinically insignificant changes (smoothing of the T wave, depression of segment ST, the expansion of the complex QRS).

Parenteral application is possible only in hospital under medical supervision, compliance with bed rest in the first days of therapy. Caution is necessary when a dramatic shift in the vertical position from the position of "lying" or "sitting". In the period of treatment should be excluded use of ethanol. Assign no earlier than 14 days after discontinuation of MAO inhibitors, beginning with small doses.

At the reception after the sudden cessation of long-term treatment may develop the syndrome of "cancellation". Dose-dependent manner lowers the threshold of convulsive readiness (used with caution in patients with epilepsy, as well as the presence of other predisposing factors, the emergence of convulsant disorders, such as traumatic brain injury of any etiology, the simultaneous use of antipsychotic drugs (neuroleptics) in the period of non-ethanol or cancel drugs with anticonvulsant properties, such as benzodiazepines). Pronounced depression of the peculiar risk of suicidal actions, which may persist until a substantial remission. In this regard, early treatment can be shown with a combination of drugs from the group of benzodiazepines, or antipsychotic drugs and constant medical control (charging proxies storage and issuing of drugs).

Many patients with panic attacks in the early treatment of increased anxiety. Such a paradoxical anxiety enhancement is most marked in the first days of therapy and usually subsides within 2 weeks. Patients with cyclic affective disorders during the depressive phase of the therapy may develop manic or hypomanic (required dose reduction or withdrawal of the drug and the appointment of antipsychotic drugs). After coping with these states, if there are indications, treatment at low doses can be reopened.

Because of the possible cardiotoxic effects need to be careful when treating patients with thyrotoxicosis or patients receiving thyroid hormone drugs. In conjunction with electroconvulsive therapy shall be appointed only with careful medical supervision.

In predisposed patients and elderly patients may provoke the development of drug psychoses, mainly at night (after the withdrawal of the drug are within a few days). Can cause paralytic ileus, mainly in patients with chronic constipation, elderly, or patients who are forced to comply with bed rest. Before general or local anesthesia should warn the anesthesiologist that the patient takes clomipramine. Because anticholinergic actions may reduce watery, and the relative increase in the number of mucus in the tear fluid, which can cause damage to the corneal epithelium in patients using contact lenses.

Prolonged use of an increase in the incidence of dental caries. The study of reproduction in animals showed adverse effects on the fetus, and adequate and strictly controlled studies in pregnant women has not been conducted.

Pregnant women should use the drug only if the intended benefits to the mother outweighs the potential risk to the fetus. Penetrates into breast milk and may cause drowsiness in infants. In order to avoid the development of the syndrome of "cancellation" in neonates (proyavlyaetya shortness of breath, drowsiness, intestinal colic, increased nervous excitability, hypotension or hypertension, tremor or spastic phenomena) receiving clomipramine gradually canceled at least 7 weeks prior to delivery.

Children compared with adults are more sensitive to acute overdosage, which should be considered dangerous and potentially lethal to them.

During the period of treatment must be careful when driving and other lesson potentially dangerous activities which require high concentration and speed of psychomotor reactions.

Drug Interactions

When the joint application of ethanol and drugs which depress the central nervous system (including other antidepressants, barbiturates, benzodiazepines and general anesthetics) may be a considerable increase in inhibitory action on the CNS, respiratory depression and hypotensive effect. Increases sensitivity to drinks containing ethanol. Increases anticholinergic effects of amantadine and other drugs with anticholinergic activity (eg phenothiazines, antiparkinsonian drugs, atropine, biperidena, antihistamine drugs), which increases the risk of side effects (from the central nervous system, eyes, intestines and bladder).

When combined with the use of antihistamine drugs, clonidine - increased inhibitory action on CNS, with atropine - increases the risk of paralytic ileus, with drugs causing extrapyramidal reactions - the severity and frequency of extrapyramidal effects.

With simultaneous application of clomipramine and indirect anticoagulants (coumarin derivatives or indadiona) may increase anticoagulant activity of the latter. Clomipramine may exacerbate depression caused by SCS.

When combined with the use of anticonvulsant drugs may be increased inhibitory action on the central nervous system, reducing the threshold of seizure activity (when used in high doses) and reduced the effectiveness of the latter. Drugs for the treatment of thyrotoxicosis increase the risk of agranulocytosis. Reduces the effectiveness of phenytoin and alpha-blockers. Inhibitors of microsomal oxidation (cimetidine), extend T1 / 2, increase the risk of toxic effects of clomipramine (may require dose reduction clomipramine 20-30%), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine, oral contraceptives) reduce the concentration in plasma and reduce the effectiveness of clomipramine. Fluoxetine and fluvoxamine increase the concentration of clomipramine in plasma (may require dose reduction clomipramine 50%).

In a joint application with holinoblokatorami, phenothiazines and benzodiazepines - are mutually reinforcing sedative and central anticholinergic effects and increased risk of epileptic seizures (threshold decrease seizure activity), phenothiazines, in addition, may increase the risk of neuroleptic malignant syndrome.

With simultaneous application of clomipramine with clonidine guanetidinom, betanidinom, reserpine and methyldopa - reduction of the hypotensive effect of the latter; with cocaine - the risk of cardiac arrhythmias. Estrogensoderzhaschie oral contraceptive drugs and estrogens may increase the bioavailability of clomipramine, antiarrhythmic drugs (such as quinidine) - the risk of arrhythmias (possibly slowing metabolism clomipramine).

Combined use of disulfiram and other inhibitors atsetaldegidrogenazy provokes delirium. Incompatible with MAO inhibitors (possible increase in the frequency of periods hyperpyrexia, severe convulsions, hypertensive crises, and the patient's death). Pimozid and probucol may increase cardiac arrhythmia, which is manifested by the lengthening of the QT interval on ECG. Enhances the effect of the SCA epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (including when these drugs are part of local anesthetics), and increases the risk of cardiac arrhythmia, tachycardia, severe hypertension.

Combined use of alpha-adrenostimulyatorov for intranasal administration, or for use in ophthalmology (with significant systemic absorption) can be amplified vasoconstrictor action of the latter.

In a joint reception with thyroid hormones - the mutual reinforcement of therapeutic effects and toxic effects (including cardiac arrhythmia and a stimulating effect on the CNS). M-holinoblokatory and antipsychotic drugs (neuroleptics) increase the risk of hyperpyrexia (especially during hot weather). Solution for injection is incompatible with diclofenac solution for injection.

At a joint appointment with other drugs may gain gematotoksichnymi gematotoksichnosti.

Terms and Conditions of storage

Store in a dark place at temperatures not above 30 ° C.

Shelf life 5 years