Anafranil (Clomipramine) tablets - Instructions for Use, Dosage, Side Effects, Reviews

Synonyms: Anafranil, Atenual, Ausentron, Clomip, Clomipramin, Clonil, Depnil, Ocifril, Ocifril-XR, Praminex, Syconil, Anafranil, Anafranil retard, Anafranil SR, Anafril, Apo-Clomipramine, Chemmart Clomipramine, Clofranil, Clomi, Clomicalm (veterinary use), Clomidep, Clomine, Clomipramin-CT, Clomipramine (chlorhydrate) Mylan, Clomipramine HCl Actavis, Clomipramine HCl CF, Clomipramine HCl Mylan, Clomipramine HCl PCH, Clomipramine HCl ratiopharm, Clomipramine HCl Sandoz, Clomipramine Hydrochloride, Clomipramine Mylan, Clomipramine Sandoz, Clomipramine Teva, Clomipramine, Clomipraminhydrochlorid 2care4, Clomipramin-neuraxpharm, Clomipramin-neuraxpharm retard, Clomipramin-ratiopharm, Clopran, Clowin, CO Clomipramine, Cosinic, Equinorm, For-You, GenRX Clomipramine, Gromin, Hydiphen, Klomipramin Merck NM, Klomipramin Mylan, Klomipramin, Maronil, Pashin, Placil, Promil, Terry White Chemists Clomipramine, Trianil.

Active substance: Clomipramine.

ATC - N06AA04 clomipramine

Pharmacological group - Antidepressants.

Nosological classification (ICD–10)

F32 Depressive episode;

F40.0 Agoraphobia;

F42 Obsessive-compulsive disorder;

F44 Dissociative [conversion] disorders;

G47.4 Narcolepsy and cataplexy;

R32 Urinary incontinence, unspecified;

R52.2 Other constant pain.

Anafranil Composition, structure and packing

Anafranil (25 mg): Coated tablets pale yellow sugar; round, biconcave.

Excipients: lactose, corn starch, colloidal silicon dioxide, stearic acid, talc, magnesium stearate, glycerol 85%, hydroxypropyl methylcellulose, vinylpyrrolidone/vinyl acetate, titanium dioxide, crystalline sucrose, polyvinylpyrrolidone K30, disperse yellow 15093 ansted (iron oxide yellow (EES172) + 5% titanium dioxide (EES171) 95%), polyethylene glycol 8000 (Macrogol 8000), microcrystalline cellulose.

Anafranil SR (75 mg): Sustained-release tablets, film-coated pink capsules, biconcave, with Valium on both sides, one side embossed “C/G”, on the other - “G/D”.

Other ingredients: calcium hydrogen phosphate dihydrate, polyacrylate dispersion 30%, calcium stearate, colloidal silicon dioxide, hydroxypropyl cellulose, talc, titanium dioxide, polyoxyl 40 hydrogenated castor oil, iron oxide red.

Pharmacological action

Tricyclic antidepressant, an inhibitor of the reuptake of norepinephrine and serotonin. It is believed that the therapeutic action is carried Anafranil due to its ability to inhibit neuronal noradrenaline (NA) and serotonin (5-HT), released into the synaptic cleft, and the most important is the inhibition of serotonin reuptake.

Anafranil furthermore inherent in a wide variety of other pharmacological activities: alpha 1-adrenolytic, anticholinergic, antihistaminic and anti-serotoninergic (blockade of 5-HT-receptors).

Anafranil works on the depressive syndrome as a whole, including especially in its typical symptoms such as psychomotor retardation, depressed mood and anxiety. The clinical effect is usually observed after 2–3 weeks of treatment.

In addition, Anafranil has a specific (different from its antidepressant effect) effect in obsessive-compulsive disorders.

Action Anafranil for chronic pain syndromes, as due and not due to physical illness, probably due to relief transmission of nerve impulses, mediated by serotonin and noradrenaline.

Pharmacokinetics

Absorption

After oral clomipramine completely absorbed from the gastrointestinal tract. Systemic bioavailability of unchanged clomipramine is about 50%. Such a reduction in bioavailability due to the effect of “first pass” through the liver to the active metabolite of N-dezmethylclomipramine. Food intake does not significantly affect the bioavailability of clomipramine. Perhaps only a slowing its absorption and hence increase the time to reach C max in the blood plasma. Anafranil (coated tablets) and Anafranil SR (sustained-release tablets, coated tablets) is bioequivalent.

After oral administration in a constant daily dose of clomipramine Css in plasma varies greatly from patient to patient.

With daily administration of 75 mg/day Css of clomipramine in the plasma is established in the range from 20 to 175 ng/ml. C ss values of the active metabolite of N-dezmethylclomipramine at 40–85% higher than that of clomipramine.

Distribution

Clomipramine binding to plasma proteins is 97.6%. The apparent Vd is about 12–17 L/kg of body weight. Concentrations of clomipramine in the cerebrospinal fluid is approximately 2% of its level in blood plasma. Clomipramine penetrates into breast milk, where it is determined at concentrations similar to the concentrations in the blood plasma.

Metabolism

Clomipramine is metabolized mainly by demethylation to the active metabolite N-decmetilklomipramina. In this reaction involves several cytochromeP–450 isozymes, but mainly CYP3A4, CYP2C19 and CYP1A2. Clomipramine and N-dezmethylclomipramine hydroxylated to 8 hydroxyclomipramine and 8-hydroxy-N-dezmethylclomipramine. Activity of hydroxy-metabolite in vivo is not defined. Clomipramine also hydroxylated in position 2; N-dezmethylclomipramine can be further demethylated to dezmethylclomipramine. 2 and 8-hydroxy metabolites are excreted predominantly in the urine as glucuronides. The elimination of the two active components - clomipramine and N-dezmethylclomipramine by forming 2 and 8 hydroxyclomipramine catalyzed CYP2D6.

Excretion

Approximately 2/3 of a single dose of clomipramine is output as the water-soluble conjugates in urine and approximately one third dose - feces. Unchanged in the urine output of about 2% of the dose of clomipramine and about 0.5% dezmethylclomipramine. T 1/2 plasma clomipramine averaging 21 hours (range of variation from 12 to 36 hours) and dezmethylclomipramine - average 36 hours.

Pharmacokinetics in special clinical situations

In elderly patients, regardless of the dose used Anafranil, due to the reduction of metabolic rate in the plasma concentration of clomipramine higher than in younger patients.

Data on the effect of functional disorders of the liver and kidneys on the pharmacokinetic parameters of clomipramine has not yet been received.

Clomipramine (Anafranil) Dosage

Doses were selected individually, taking into account the patient’s condition. The goal of treatment is to achieve an optimal effect on the background of the lowest possible doses of the drug, as well as their gentle increase, especially in elderly patients and adolescents, which are generally more sensitive to Anafranil than those of intermediate age groups.

Before therapy should eliminate hypokalemia.

In depression, obsessive-compulsive syndrome and phobias initial daily dose is 75 mg (25 mg 2–3 times/day) or Anafranil 75 mg 1 time/day Anafranil Wed Then, during the first week of treatment, the dose was gradually increased, e.g., 25 mg every several days (depending on tolerance) to achieve the daily dose is 100–150 mg. In severe cases, the daily dose may be increased to a maximum of 250 mg. Once improvement is achieved, the patient is transferred to a maintenance dose of the drug, is 50–100 mg (2–4 tablets. Anafranil or 1 tab. Anafranil SR).

For panic disorder, agoraphobia, the initial dose is 10 mg/day. Then, depending on the tolerability Anafranil, the dose was increased to achieve the desired effect. The daily dose varies considerably and may range from 25 mg to 100 mg. When necessary, may increase the dose to 150 mg/day. It is recommended not to stop the treatment for at least 6 months, slowly decreasing during this time a maintenance dose of the drug.

When cataplexy accompanying narcolepsy, a daily dose of 25–75 mg Anafranil.

In chronic pain syndromes Anafranil dose should be adjusted individually. The daily dose varies considerably and may range from 10 mg to 150 mg. It should take into account the concomitant analgesics and the ability to reduce the use of the latter.

In elderly patients, the initial dose is 10 mg/day. Then slowly, for about 10 days, the daily dose is increased to an optimum level which is 30–50 mg.

Children and adolescents

For obsessive-compulsive syndromes, the initial dose is 25 mg/day. During the first 2 weeks the dose was gradually increased, as tolerated, until a daily dose of 100 mg, or the calculated rate of 3 mg/kg body weight, depending on whether the dose is less. Over the next several weeks of dosage continuing to gradually increase until reaching a daily dose of 200 mg, or the calculated rate of 3 mg/kg body weight, depending on whether the dose is less.

When nocturnal enuresis initial daily dose of Anafranil for children aged 5–8 years is 20–30 mg; for 9–12 year olds - 25–50 mg; for children over 12 years - 25–75 mg. The use of higher doses indicated for patients who have no clinical effect complete after 1 week of treatment. Usually, all the daily dose administered in one go after dinner, but when involuntary urination noted in the early hours of the night, the dose prescribed Anafranil before - in 16 hours. After achieving the desired effect of treatment should be continued for 1–3 months, gradually reducing the dose of Anafranil.

Anafranil Overdose

Symptoms developing in overdose Anafranil, are similar to those described in cases of overdose of other tricyclic antidepressants. The main complications are violations of the activity of the heart and neurological disorders. Children welcome random drug at any dose should be considered as inside a very serious and threatening fatal event.

Symptoms usually appear within 4 hours after administration and reaches a maximum expression after 24 hours. Due depot (anticholinergic drug action), a prolonged half-life and hepato-enteric recycling of active substance, the time period during which the patient remains in the “risk zone” is 4–6 days.

CNS: drowsiness, stupor, coma, ataxia, restlessness, agitation, increased reflexes, muscle rigidity, horeoatetoidnye movement, convulsions. In addition, there may be manifestations of serotonin syndrome (fever, myoclonus, delirium, coma).

Cardio-vascular system: marked reduction in blood pressure, tachycardia, prolongation of the interval QT c, arrhythmia (including ventricular arrhythmias such as “pirouette”) breach of intracardiac conduction, shock, heart failure; in very rare cases - cardiac arrest.

Other: possible respiratory depression, cyanosis, vomiting, fever, mydriasis, sweating, oliguria or anuria.

Treatment: No specific antidote does not exist, the treatment is mainly symptomatic and supportive. If you suspect an overdose of Anafranil, especially in children, the patient should be hospitalized and closely monitored for a minimum of 72 hours.

If the patient is conscious, you should as soon as possible to gastric lavage or induce vomiting. If the patient is unconscious, before the start of gastric lavage for the prevention of aspiration should be performed tracheal intubation using a tube with a cuff; vomiting in this case do not cause. These measures are recommended in case of overdose has passed since 12 hours and even more, since anticholinergic effects Anafranil may slow gastric emptying. To slow the absorption of the drug is useful to use activated carbon.

Treatment is based on the application of modern methods of intensive therapy with constant monitoring of heart function, gas composition, and blood electrolytes, as well as on the application, if necessary urgent measures such as anticonvulsant therapy, mechanical ventilation and resuscitation techniques. Since then, as it was reported that physostigmine may cause severe bradycardia, asystole, and seizures, use of this drug for the treatment of overdose Anafranil is not recommended. Hemodialysis and peritoneal dialysis are not effective because clomipramine concentration in plasma is low.

Drug Interactions

Pharmacodynamic interaction

Anafranil can reduce or completely eliminate the antihypertensive effect guanethidine, betanidina, reserpine, clonidine and alpha-methyldopa. Therefore, in cases where both the reception Anafranil requires treatment of hypertension, it is necessary to use other classes of drugs (e.g., vasodilators and beta blockers).

Tricyclic antidepressants, including Anafranil may potentiate the effect of anticholinergic agents (eg, phenothiazines, antiparkinson drugs, atropine, biperiden, antihistamines) on the organ of vision, central nervous system, intestines and bladder.

Tricyclic antidepressants may potentiate the effects of ethanol and other agents having a depressing effect on the central nervous system (eg, barbiturates, benzodiazepines or anesthetic drugs).

Anafranil should not be administered for at least 2 weeks after discontinuation of MAO inhibitors because of the risk of such severe symptoms and conditions such as hypertensive crisis, increased body temperature, as well as the symptoms of serotonin syndrome: myoclonus, agitation, seizures, delirium and coma. The same rule should be followed in the event that an MAO inhibitor is administered after previous treatment of Anafranil. In any of these cases, the initial dose or Anafranil MAO inhibitors should be low, they should increase gradually under constant drug effects.

The existing experience shows that Anafranil may be appointed not earlier than 24 hours after discontinuation of MAO inhibitors type A reversible actions (such as moclobemide). However, if MAO inhibitor type A is assigned after the abolition of Anafranil, recess should be at least 2 weeks.

The combined use of Anafranil with selective serotonin reuptake inhibitors may lead to increased action on the serotonin system.

With simultaneous use of Anafranil with selective serotonin reuptake inhibitors or serotonin reuptake inhibitors and noradrenaline (norepinephrine), tricyclic antidepressants and lithium therapy may develop serotonin syndrome with symptoms such as fever, myoclonus, agitation, convulsions, delirium, and coma.

The appointment of fluoxetine is recommended to do a two-week break between the use of Anafranil and fluoxetine - finish fluoxetine to 2–3 weeks prior to initiation of therapy with Anafranil or assign fluoxetine 2–3 weeks after completion of treatment of Anafranil.

Anafranil may potentiate the cardiovascular system sympathomimetics (epinephrine, norepinephrine, isoprenaline, phenylephrine and ephedrine), including: and when these materials are part of local anesthetics.

Pharmacokinetic interactions

The active ingredient of the drug Anafranil - clomipramine - mainly excreted as metabolites. The main metabolic pathway - demethylation to the active metabolite of N-dezmethylclomipramine followed by hydroxylation and conjugation of N-dezmethylclomipramine with clomipramine. In demethylation involves several cytochromeP–450, mainly CYP3A4, CYP2C19 and CYP1A2. The elimination of two active components by hydroxylation is catalyzed by CYP2D6.

Co-administration with inhibitors of CYP2D6 isoenzyme may lead to increased concentrations of both active ingredients to three times the value of the phenotype in patients with rapid metaboliser debrisoquine/sparteine. In this case, the metabolism in these patients is reduced to the level typical for people with poor metabolizer phenotype.

It is assumed that co-administration with inhibitors of CYP1A2, CYP2C19 and CYP3A4 may lead to increased concentrations of clomipramine and lower concentrations of N-dezmethylclomipramine.

MAO inhibitors (eg moclobemide) are contraindicated when taking klomipamina because in vivo, they are potent inhibitors of CYP2D6.

Antiarrhythmic drugs (eg quinidine and propafenone) should not be used in conjunction with tricyclic antidepressants, since they are potent inhibitors of CYP2D6.

Selective serotonin reuptake inhibitors (such as fluoxetine, paroxetine, or sertraline) inhibit CYP2D6, other preparations of this group (e.g. fluvoxamine) also inhibit CYP1A2, CYP2C19, which may lead to an increase in the plasma concentration of clomipramine and development of relevant adverse effects. There was a 4-fold increase in the equilibrium concentration of clomipramine during coadministration with fluvoxamine (the concentration of N-dezmethylclomipramine decreased 2-fold).

The combined use of neuroleptics (eg phenothiazines) may increase the plasma concentrations of tricyclic antidepressants reduce seizure threshold and cause seizures. Combination with thioridazine may lead to the development of severe cardiac arrhythmias.

Combined use of histamine H2-receptor cimetidine (which is an inhibitor of some cytochromeP–450, including CYP2D6 and CYP3A4) may result in increased plasma concentrations of tricyclic antidepressants, and therefore requires a dose reduction of the latter.

There are no data confirming interaction between of Anafranil (25 mg/day) and oral contraceptives (15 or 30 mg of ethinyl estradiol/day) at constant reception latter. There is no evidence that estrogens are inhibitors of CYP2D6 - the main isoenzyme involved in the elimination of clomipramine, so there is no reason to expect their interaction. Although concomitant use of tricyclic antidepressant imipramine and estrogen in high doses (50 mg/d) in some cases reported worsening of side effects and enhancing the therapeutic effect of an antidepressant. It is not known whether these findings are significant in relation to the simultaneous use of clomipramine and estrogen in low doses. In joint use of tricyclic antidepressants and high doses of estrogen (50 mg/day) recommended monitoring therapeutic effect of antidepressants and, if necessary, correction mode.

Methylphenidate may promote increased concentrations of tricyclic antidepressants, possibly by inhibiting their metabolism. In a joint application of these drugs may increase the concentration of tricyclic antidepressants in the blood plasma, while you may need to decrease the dose of the latter.

Some tricyclic antidepressants may increase the anticoagulant effect of coumarins (eg, warfarin), possibly by inhibiting their metabolism (CYP2C9). There is no evidence to prove the ability to inhibit the metabolism of clomipramine anticoagulants (warfarin). However, when using this class of drugs is recommended monitoring plasma concentration of prothrombin.

Co-administration with drugs Anafranil - inducers of cytochromeP–450, especially CYP3A4, CYP2C19 and/or CYP1A2 may increase the metabolism and reduce the effectiveness of Anafranil.

Co-administration with drugs Anafranil - inducers of CYP3A and CYP2C, such as rifampicin or anticonvulsants (eg, barbiturates, carbamazepine, phenobarbital and phenytoin), may lead to a decrease in the concentration of clomipramine in plasma.

Known inducers of CYP1A2 (for example, nicotine/other components of cigarette smoke) lower concentrations of tricyclic antidepressants in the blood plasma. The equilibrium concentration of clomipramine cigarette smokers persons 2 times lower than that of non-smokers (the concentration of N-dezmethylclomipramine not changed).

Clomipramine, as in vivo, or in vitro, inhibits CYP2D6 (sparteine oxidation). Thus, clomipramine may increase the concentration of both of the drugs metabolized mainly involving CYP2D6, in patients with extensive metabolizer phenotype.

Pregnancy and lactation

Experience of using Anafranil in pregnancy is limited. Since there are anecdotal reports of a possible association between tricyclic antidepressants and impaired fetal growth, Anafranil should be avoided during pregnancy, except in cases where the expected effect of treatment of the mother clearly outweighs the potential risk to the fetus.

In cases where the tricyclic antidepressants used during pregnancy up until the birth, the newborn during the first few hours or days of developing the syndrome, which is manifested by shortness of breath, lethargy, colic, irritability, hypotension or hypertension, tremors, spastic phenomena or convulsions. To avoid the development of this syndrome Anafranil should be possible to gradually canceled at least 7 weeks prior to delivery.

Since the active ingredient of the drug is excreted in breast milk, you should either stop breastfeeding or gradually abolish Anafranil.

Anafranil Side effects

Adverse reactions are listed by frequency, beginning with the most common: occur very often (≥10%); often (≥1%, but <10%); sometimes (≥0.1%, but <1%); rarely (≥0.01%, but <0.1%); very rarely (<0.01%, including isolated cases).

CNS and peripheral nervous system. Mental status: very often - drowsiness, fatigue, restlessness, increased appetite; often - confusion, disorientation, hallucinations (especially in elderly patients and in patients with Parkinson’s disease), anxiety, agitation, insomnia, mania, hypomania state, aggression, memory impairment, depersonalization, increased depression, impaired concentration, insomnia, nightmares, yawning; sometimes - activation of psychotic symptoms. Neurological status: very often - dizziness, tremor, headache, myoclonus; often - delirium, speech disturbances, paresthesia, muscle weakness, increased muscle tone; sometimes - convulsions, ataxia; very rare - EEG changes, increased body temperature.

Effects due to the anticholinergic activity: very often - dry mouth, increased sweating, constipation, accommodation disturbances, blurred vision (“blurred vision”), voiding; often - flushing, mydriasis; very rare - glaucoma, urinary retention.

Cardio-vascular system: often - sinus tachycardia, palpitations, orthostatic hypotension, clinically insignificant changes in the ECG (eg, ST interval or tooth T) in patients without heart disease; sometimes - arrhythmias, increased blood pressure; very rarely - violation of intracardiac conduction (eg, expansion of the complex QRS, lengthening the interval QT, change the interval PQ, block bundle-branch block, ventricular tachycardia bidirectional fusiform/ventricular arrhythmias such as “pirouette” /), especially in patients with hypokalemia).

From the digestive system: very often - nausea; often - vomiting, abdominal discomfort, diarrhea, anorexia, increased transaminase levels; rarely - hepatitis with jaundice or without it.

Dermatological reactions: often - allergic skin reactions (rash, urticaria), photosensitivity, pruritus; very rare - edema (local or general), hair loss.

Part of the endocrine system and metabolism: very often - an increase in body weight, disturbances of libido and potency; often - galactorrhea, increase in the mammary glands; very rarely - a syndrome of inappropriate secretion of antidiuretic hormone.

Hypersensitivity reactions: rarely - allergic alveolitis (pneumonitis) with or without eosinophilia, systemic anaphylactic/anaphylactoid reactions, including hypotension.

Hematopoietic system: rarely - leukopenia, agranulocytosis, eosinophilia, thrombocytopenia, purpura.

From the senses: common - a violation of taste, tinnitus.

Other: after abrupt withdrawal or rapid dose reduction Anafranil often experience the following symptoms: nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, irritability, anxiety.

The observed adverse events were usually mild and transient, are in the continuation of treatment or after dose reduction Anafranil. They do not always correlate with the concentration of the active drug substance in the blood plasma or its dose. Some adverse events such as general weakness, sleep disturbances, agitation, anxiety, constipation, dry mouth, it is often difficult to distinguish from depression.

In case of serious side effects from the nervous system or mental status Anafranil should be abolished.

The elderly are particularly susceptible to the action of Anafranil on the nervous system, cardiovascular system, and the effect of the drug on mental status, as well as anticholinergic effects Anafranil. Metabolism and excretion of drugs in this age may slow down, which leads to higher drug concentrations in blood plasma, even when used in high therapeutic doses.

Indications

Adults

The treatment of depressive states of different etiology, occurring with varying symptoms as endogenous, reactive, neurotic, organic, masked, involutional forms of depression; depression in patients with schizophrenia and psychopathy; depressive syndromes that occur in old age due to chronic pain or chronic physical illness; depressive disorders mood reactive, neurotic or psychopathic nature;

Obsessive-compulsive syndromes;

Chronic pain syndrome;

Phobias and panic attacks;

Cataplexy, accompanying narcolepsy.

Children and adolescents

Obsessive-compulsive syndromes;

Nocturnal enuresis (only in patients over the age of 5 years and subject to the exclusion of organic causes of disease).

Prior to initiating therapy with Anafranil nocturnal enuresis in children and adolescents should assess the value of the potential benefits and risks for the patient. Should consider the possibility of alternative therapy.

Currently not received sufficient evidence of efficacy and safety of clomipramine in children and adolescents for the treatment of depressive states of various etiology, occurring with varying symptoms, phobias and panic attacks, cataplexy accompanying narcolepsy and chronic pain. Therefore the use of Anafranil in children and adolescents (0–17 years) for these indications is not recommended.

Contraindications

Hypersensitivity to clomipramine and other ingredients, cross-hypersensitivity to tricyclic antidepressants from the group dibenzazepine;

Simultaneous use of MAO inhibitors, and the period of less than 14 days before and after use;

Simultaneous use of selective inhibitors of MAO-A reversible actions (such as moclobemide);

Recent myocardial infarction;

Congenital syndrome prolongation of the interval QT.

Do not use the drug during pregnancy and breastfeeding.

The drug is not recommended for use in children under the age of 5 years. Cautions

It is known that tricyclic antidepressants reduce seizure threshold, so Anafranil should be used with extreme caution in patients with epilepsy, as well as the presence of other predisposing to seizures of factors, such as traumatic brain injury of any etiology, the simultaneous use of antipsychotics during the period of refusal alcohol or drug withdrawal, with anticonvulsant properties (eg, benzodiazepines). It is believed that the occurrence of seizures while taking Anafranil depends on the dose of the drug. In this regard, should not exceed the recommended daily dose Anafranil.

Special care should be given to patients with Anafranil cardiovascular diseases, especially cardiovascular insufficiency, intracardiac conduction disturbances (eg, AV-blockade of I-III degree) or arrhythmias. In these patients, as well as in elderly patients, it is necessary to regularly monitor the performance of the heart and ECG.

Before therapy of Anafranil recommended to measure blood pressure, as in patients with orthostatic hypotension or lability of the cardiovascular system may be a sharp decline in blood pressure.

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

Because of the anticholinergic actions characteristic of tricyclic antidepressants may reduce tearing and accumulation of mucus secretion, which can result in damage to the corneal epithelium in patients who use contact lenses.

Caution is needed in the treatment of tricyclic antidepressants in patients with severe liver disease, and in patients with tumors of the adrenal medulla (eg, pheochromocytoma, neuroblastoma), t. To., In this case, these drugs can provoke the development of hypertensive crisis.

It is known that in patients with cyclic affective disorders receiving tricyclic antidepressants, during the depressive phase may develop manic or hypomanic state. In such cases it may be necessary to decrease the dose Anafranil or its cancellation and antipsychotic therapy. After the relief of these conditions, if there are indications, treatment of Anafranil in low doses may be resumed.

In predisposed patients and elderly patients, tricyclic antidepressants can provoke the development of drug delirious psychosis, mainly at night. After discontinuation these disorders resolve within a few days.

Caution should be exercised when treating patients with hyperthyroidism, or receiving thyroid hormone drugs, which may have cardiotoxic effects.

Although changes in the level of white blood cells during treatment of Anafranil reported only in individual cases, it is recommended periodic study of peripheral blood and attention to symptoms such as fever and sore throat, especially in the first months of therapy or long-term use of the drug.

Caution is needed when using Anafranil in patients with chronic constipation. Tricyclic antidepressants may cause paralytic ileus, mainly in elderly patients or in patients who have to comply with bed rest.

In the application of Anafranil at doses higher than average therapeutic, or if the concentration of clomipramine in plasma exceeds the average therapeutic, there is a risk of QTc and QT c occurrence of ventricular tachycardia bidirectional spindle (ventricular arrhythmias such as “pirouette”). This is observed in the case of co-administration with selective serotonin reuptake inhibitors or serotonin reuptake inhibitors and norepinephrine. In this regard, it is necessary to avoid sharing clomipramine and preparations causing its cumulation. You should also avoid co-administration with drugs that cause lengthening of the interval QT c. Diuretics can lead to hypokalemia. Established that hypokalaemia is a risk factor for QT c interval prolongation and the occurrence of ventricular tachycardia bidirectional spindle (ventricular arrhythmias such as “pirouette”). Therefore, hypokalemia should be corrected before initiating therapy of Anafranil. Anafranil should be used with caution in conjunction with selective serotonin reuptake inhibitors or serotonin reuptake inhibitors and norepinephrine, as well as a diuretic.

Due to the risk of serotonin toxicity should follow the recommended dose and increase the dose with caution if Anafranil is used in conjunction with serotonergic drugs.

With simultaneous use of Anafranil with serotonergic drugs such as selective serotonin reuptake inhibitors, serotonin reuptake inhibitors and norepinephrine, tricyclic antidepressants or lithium, may develop serotonin syndrome with symptoms such as fever, myoclonus, agitation, convulsions, delirium, and coma. The appointment of fluoxetine, it is recommended to do a two-week break between the use of Anafranil and fluoxetine.

Many patients with panic disorder at baseline of Anafranil enhanced anxiety. Such a paradoxical increased anxiety is most pronounced in the first days of therapy and usually subsides within two weeks.

In patients with schizophrenia receiving tricyclic antidepressants, sometimes marked activation of psychosis.

In patients with liver disease is recommended periodic monitoring of liver enzymes.

Anafranil, as well as other tricyclic antidepressants administered in combination with electroconvulsive therapy only with careful medical supervision.

Severe depression peculiar risk of suicidal acts, which may persist until remission reliable. Patients with depression in adults and children, there may be increased depression and/or suicidal behavior or other psychiatric symptoms, regardless of whether they receive antidepressant medication or not. Antidepressants increased the risk of suicidal thoughts and suicidal behavior in short-term studies in children and adolescents with depression and other psychiatric disorders.

All patients taking Anafranil on any of the readings should be evaluated for clinical worsening, suicidal behavior and other psychiatric symptoms, especially in the initial phase of therapy or when changing the dose. These patients should be considered the possibility of changing therapy, including the possible removal of the drug, especially if such changes pronounced, appeared suddenly or have not been observed in patients initially.

Families and caregivers of patients (both children and adults) who take antidepressants for psychiatric or non-psychiatric indications, should be alerted about the need to monitor patients because of the risk of other psychiatric symptoms, including and suicidal behavior, and immediately report such symptoms to physicians.

When prescribing Anafranil should specify the minimum number of tablets to reduce the risk of overdose. It is necessary to observe adequate regimen.

There is evidence that in patients receiving Anafranil had fewer deaths due to overdose, than in patients receiving other tricyclic antidepressants.

Prior to the general or local anesthesia, the anesthetist should be warned that the patient is taking Anafranil.

Reported an increase in the incidence of dental caries in long-term treatment with tricyclic antidepressants. Therefore, in the case of long-term therapy of Anafranil recommended regular inspection of the patient’s dentist.

Diuretics can lead to hypokalaemia, in which the risk of QTc and QT c fusiform appearance bidirectional ventricular tachycardia (type “pirouette”). Prior to initiating therapy of Anafranil should be the correction of hypokalemia.

Avoid abrupt withdrawal Anafranil since This may lead to side reactions. If you decide to discontinue treatment, medication should be withdrawn gradually, as soon as it allows the clinical situation. Please keep in mind that the abrupt withdrawal of the drug may lead to the development of certain symptoms.

Film-coated tablets, 25 mg contain lactose and sucrose. Patients with rare hereditary diseases, such as galactose and fructose intolerance, severe lactase deficiency, sucrase-izomaltaznaya deficiency or glucose-galactose malabsorption should not take Anafranil tablets, coated tablets.

Keep in mind that alcohol may enhance the adverse effects of the CNS, such as blurred vision, drowsiness.

Use in Pediatrics

Experience with Anafranil in children under the age of 5 years are not available, it is not recommended to use the drug in children of this age group.

Effects on ability to drive vehicles and management mechanisms

Patients who during treatment with Anafranil arise drowsiness and other CNS side effects (including blurred vision), you should not drive a car, operate machinery, or engage in other activities that require attention and fast reaction.

Anafranil Review

Most excellent antidepressant, Anafranil inexpensive (packing - 30 tablets). I am a second time, "I go" to this drug, the first time "enough" for three years plus get rid of panic attacks (PA). I take three tablets at night (started with a ten-day course of injections).
From Side effects - tachycardia heart rate of 100-120 beats / min, blood pressure fluctuations (100-135 / 60-90). The first "approach" has been gaining weight (10 kg for 3 months), now weight gain absolutely not.

Anafranil decreased anxiety, a desire to do something, and all this after the third week of admission in tablet form, excluding the ten-day course of injections. I know people who for several years, "sit" on Anafranil and feel great.

Familiarity with Anafranil occurred in the hospital Alekseeva, where I got my horrible panic attacks. The first appointment was with no side effects, I am very easy on him, "the village" and as he became a great help. A year has passed without a panic attack treatment Anafranil was six months, in addition to him were antipsychotics, tranquilizers and correctors naturally. full nabor.all inclusive so to speak. When aggravation happened, I again began to take Anafranil. but something went wrong. the first tablet I started sausage as if I used some powerful drug. appearance corresponded to that feeling. Huge pupils, trembling hands, a lot of energy from a well, too bad, you do not know where to go, a terrible panic, tachycardia, and a state of the week for sure! A week side effects go and begins to act Anafranil. a month of reception you can feel the effect of this ancient antidepressant. good mood, there is no fear, a lot of positive energy, a lot of strength, up early, good night's sleep, a great performance. The drug actually helps, but to sustain these side effecrs during the week, or even two (I saw it once 5 courses and side effects was not only the first time, other times - horrible) is very difficult. That is, how did I- week at home, in bed, on half a tablet a day, then you can get out of bed. a week later on the whole, and then the doctor ordered, I drank 2 tablets per day. This is the only antidepressant that helped me (a lot of different generations of antidepressants has been tried), but had to abandon it, strength to endure the first week no longer.