Anafranil - instructions for use, dose, side effects, contraindications

active ingredient - clomipramine hydrochloride 25 mg, and also auxiliary substances: lactose, corn starch, silicon dioxide, colloid anhydrous, stearic acid, talc, magnesium stearate, glycerol (85%), hydroxypropylmethylcellulose, vinyl pyrrolidone / vinyl acetate copolymer, titanium dioxide, sucrose crystalline, polyvinylpyrrolidone KZO, disperse yellow 15093 ansted (iron oxide yellow [EEC 172] 5 % + titanium dioxide 95% [EEC171]), polyethylene glycol
8000 (macrogol 8000), microcrystalline cellulose.

Description:Pills covered shell 25 mg: light yellow colors, toburrs, biconvex pills, covered with sugar shell.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

Clomipramine

Pharmacodynamics:

Anaphranil acts on the depressive syndrome in general, including such typical manifestations as psychomotor inhibition, 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) action in obsessive-compulsive disorders.

The action of Anafranil in chronic pain syndromes, both conditioned and not caused by somatic diseases, is probably associated with the relief of nerve impulse transmission mediated by serotonin and noradrenewhetherbutm

Pharmacokinetics:

Suction

Clomipramine is completely absorbed from the gastrointestinal tract (GIT). Systemic bioavailability of unchanged clomipramine is about 50%. This decrease in bioavailability is due to the effect of "first passage" through the liver to form an active metabolite N-desmethylclomipramine. The intake of food does not significantly affect the bioavailability of clomipramine. Perhaps only a slight slowing of its absorption and, consequently, an increase in the time to reach the maximum concentration in the blood plasma (FROM mOh). Anafranil and Anafranil CP are bioequivalent. When taking the drug inside at a constant daily dose, the equilibrium concentrations Clomipramine in plasma significantly varies in different patients.With daily administration of the drug at a dose of 75 mg / day, the equilibrium concentration of clomipramine in Plasma is set in the range from 20 to 175 ng / ml. The values of the equilibrium concentration of the active metabolite of N-desmethylclomipramine is 40-85% higher than the concentration clomipramine.

Distribution

The association of clomipramine with plasma proteins is 97.6%. Apparent volume
distribution is about 12-17 l / kg body weight. Concentrations of clomipramine in
The cerebrospinal fluid is about 2% of its concentrations in the blood plasma.
Clomipramine penetrates into the mother's milk, where it is determined in concentrations close to plasma concentrations of bloodand.

Metabolism

Clomipramine is metabolized mainly by demethylation to form an active metabolite N-desmethylclomipramine. Several cytochrome P450 isoforms participate in this reaction, but mostly CYP3A4, CYP2C19 and CYP1A2. Clomipramine and N-desmethylclomipramine are hydroxylated to 8-hydroxyclomipromine or 8-hydroxy-N-desmethylclomipramine. The activity of 8-hydroxymetabolites in vivo not determined.
Clomipramine is also hydroxylated at position 2; N-desmethylclomipramine may subsequently be demethylated to didesmethylclomipramine. 2- and 8-hydroxymetabolites are excreted mainly in the form of glucuronides with urine. Elimination of two active components: clomipramine and N-desmethylclomipramine by the formation of 2- and 8-hydroxyclomipramine is catalyzed CYP2D6.

Excretion After a single dose of Anaphranil, about 2/3 of clomipramine is excreted as
water-soluble conjugates with urine and about 1/3 - with feces. Unchanged in the urine, about 2% of the dose of clomipramine and about 0.5% of desmethylclomipramine are excreted. The half-life of plasma (T1 / 2) Clomipramine averages on average 21 hours (range from 12 up to 36 hours), T1 / 2 desmethylclomipramine - an average of 36 hours.

PharmatoOKandnetitobut in individual patient groups

In elderly patients due to reduced metabolic rate
Clomipramine concentrations in plasma are higher than in younger patients, regardless of the dose of Anafranil used. Data on the effects of violations of the liver and kidneys on the pharmacokinetic parameters of clomipramine have not been obtained to date.

Indications:

Adults

- Treatment depressive states different etiology, ongoing from various symptomatology:

=> 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 illness;

=> Depressive mood disorders are reactive, neurotic, or
psychopathic nature.

Obsessive-compulsive syndromes.

Chronic pain syndrome.

Phobias and panic attacks.

Cataplexy concomitant with narcolepsyand.

Children and teens

Obsessive-compulsive syndromes.

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

Before the initiation of therapy with anaphranil at night enuresis in children and adolescents, the relationship between potential benefit and risk for the patient should be assessed. Consider the possibility of alternative therapiesand.

At present, there is insufficient evidence of the efficacy and safety of clomipramine in children and adolescents in the treatmentdepressive states of various etiology, taking place with various symptoms, phobias and panic attacks, cataplexy, concomitant narcolepsy and chronic pain syndrome. Therefore, the use of Anafranil in children and adolescents (0-17 years) with these indications is not recommended.

Contraindications:

Hypersensitivity to clomipramine or any other ingredient in the drug, a cross-sensitivity to tricyclic antidepressants from the dibenzazepine group.

Simultaneous use of monoamine oxidase inhibitors (MAO), as well as a period of less than 14 days before and after their use. Contraindicated also the simultaneous use of selective MAO-A inhibitors of reversible action, such as moclobemide.

Recently suffered myocardial infarction. Congenital syndrome of prolongation of the QT-interval.

Do not recommend the use of the drug during pregnancy and during breastfeeding (see the section "With caution"). Ppenapat are not recommended for use in children under 5 years of age (see section "C
caution ").

Carefully:

It is known, that in patients with cyclical affective disorders receiving tRycyclic entIdeperefromsants, in PThe period of depressive phase can develop manic or hypomanic states. In such cases, it may be necessary to reduce the dose of Anafranil or in its cancellation and administration of antipsychotic therapy. After stopping these states, if there are indications, treatment with anaphranil in low doses can be resumed.
In predisposed patients and elderly patients, tricyclic
antidepressants can provoke the development of medicinal delirious psychoses,
mainly at night. After the drug is discontinued, these disorders take place within a few days.

With extreme caution, Anafranil should be prescribed to patients with cardiovascular disease, primarily with cardiovascular failure, impaired intracardiac conduction (eg, atrioventricular blockade I-III degree) or arrhythmias. In such patients, as well as in elderly patients, it is necessary to regularly monitor cardiac and ECG performance.

Before starting therapy with anaphranil, it is recommended to measure blood pressure, as patients with orthostatic hypotension or lability of the cardiovascular system may experience a sharp decrease in blood pressure.

It is known that tricyclic antidepressants reduce the threshold of convulsive readiness, therefore Anafranil should be used with extreme caution in patients with epilepsy, as well as in the presence of other factors predisposing to the onset of convulsive syndrome, for example, brain damage of various etiologies, simultaneous use of neuroleptics, from alcohol or withdrawal of drugs,
possessing anticonvulsant properties (for example, benzodiazepines). It is believed that the occurrence of seizures in the background of the use of Anafranil depends on the dose of the drug. In this regard, do not exceed the recommended daily dose of Anafranil.
Because the drug has anticholinergic properties, it should be used with extreme caution in patients who have a history of increased intraocular pressure, angle-closure glaucoma, or urinary retention (eg, due to prostate disease).

Due to the anticholinergic action characteristic of tricyclic antidstressors,
possibly reducing tearing and accumulation of mucous secretions, which can lead to damage to the corneal epithelium in patients using contact lenses.
Caution is required when treating tricyclic antidepressants in patients with severe hepatic impairment, as well as in patients with adrenal medulla tumors (eg, pheochromocytoma, neuroblastoma), since in this case, these drugs can provoke the development of a hypertensive crisis.

Care should be taken when treating patients suffering from hyperthyroidism or receiving thyroid hormone medications that may have cardiotoxic effects.

Caution is necessary when using Anafranil in patients with chronic constipation. Tricyclic antidepressants can cause a paralytic intestinal
obstruction, mainly in elderly patients or in patients,
forced to comply with bed rest.

Although changes in the level of leukocytes during the treatment with anaphranil have been reported only in selected cases, periodic study of the composition of peripheral blood and attention to symptoms such as fever and sore throat are recommended, especially in the first months of therapy or with prolonged use of the drug.

Pregnancy and lactation:

Experience of applyingeAnafranil withelimited. Because there are separate messages about the possibleMr.th relationship between Ptricyclic antidepressants and Mr.fetal development disorders, Anafranil should be avoided during pregnancy, unless the expected benefit to the mother clearly exceeds the potential risk to the fetus.

In those cases when the mother took tricyclic antidepressants during pregnancy until the onset of labor, in newborns during the first few hours or days of life, withdrawal syndrome developed, dyspnea, drowsiness, intestinal colic, increased nervous excitability, marked increase or pronounced
lowering blood pressure, tremors, spasms or seizures. To avoid the development of this syndrome, Anafranil should, if possible, be gradually canceled, at least 7 weeks before the expected delivery.

Since the active substance of the drug penetrates into breast milk, you should either stop breastfeeding, or gradually cancel Anafranil.

Dosing and Administration:

Before starting therapy, hypokalemia should be eliminated (see "With caution").

The dosage regimen and the way of using the drug are set individually, taking into account the patient's condition. The goal of the treatment is to achieve the optimal effect when using the lowest possible doses of the drug and carefully increasing them. Special care should be taken with increasing doses in elderly patients and adolescents, who are generally more sensitive to anaphranil than patients in intermediate age groupsP.

Depression, obsessive-compulsive syndromes and phobias

The initial daily dose is 75 mg; prescribe Anafranil 25 mg 2-3 times a day or Anafranil CP 75 mg once a day (preferably in the evening). Then, during the first week of treatment, the dose of the drug is gradually increased, for example, by 25 mg every few days (depending on tolerability), until a daily dose of 100-150 mg. In severe cases, the daily dose can be increased to a maximum of 250 mg. After the improvement is achieved, the patient is transferred to a maintenance dose of 50-100 mg (2-4 tablets Anafranil or 1 tablet Anafranila CP).

Panic attacks, agoraphobia

The initial dose of Anafranil is 10 mg per day. Then, depending on the tolerability of Anafranil, its dose is increased to achieve the desired effect. The daily dose of Anafranil varies greatly and can range from 25 mg to 100 mg. If necessary, a dose increase up 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.

Cataplexy accompanying narcolepsy

The daily dose of Anafranil is 25-75 mg.

Chronic Pain Syndromes

The dosage regimen is set individually. The daily dose of Anafranil varies greatly and can range from 10 mg to 150 mg. In this case, the concomitant use of analgesic drugs and the possibility of reducing the use of the latter should be considered.

Elderly patients

The initial dose is 10 mg per day. Then gradually, approximately for 10 days, the daily dose of the drug is raised to the optimal level, which is 30-50 mg.

Children and teens

The obsessive-toaboutmpulseandsyndromes

The initial dose is 25 mg / day. During the first 2 weeks, the dose is gradually increased,
taking into account tolerability, until a daily dose is reached or equal 100 mg, or calculated at 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 Anafranil is prescribed earlier - in 16 hours. After the desired
effect treatment should continue for 1-3 months, gradually reducing the dose of Anafranil.

Side effects:

The observed adverse events are usually mild and transitory, occur during the continuation of treatment or after a reduction in the dose of Anafranil.They do not always correlate with the concentration of the active substance in the blood plasma or with the dose of the drug. Some undesirable phenomena, such as fatigue, sleep disorders, agitation, anxiety, constipation, dry mouth, are often difficult to distinguish from manifestations of depression.

In case of serious reactions from the nervous system or mental status Anafranil should be canceled.

Elderly people are particularly sensitive to the action of Anafranil on the nervous system, cardiovascular system, the effect of the drug on mental status, and also on the anticholinergic effect of Anafranil.

Metabolism and excretion of drugs at this age can be slowed down, which leads to an increase in the concentration of drugs in the blood plasma when using therapeutic doses.

Undesirable reactions are listed by frequency, starting with the most frequentx: emerging
"Often" - ≥ 1/10, "often" - ≥1/100-<1/10, "sometimes" - 1 / 1000- <1 /100, "rarely" - 1 / 10000- <1 /1000, "very rarely" - <1 /10000, including individual cases.

From the central and peripheral nervous system. Mental status: very often - drowsiness, a sense of fatigue, anxiety,increased appetite; often confusion, disorientation, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, agitation, sleep disorders, manic state, hypomanic state, aggressiveness, memory impairment, depersonalization, increased depression, attention deficit disorder, insomnia, nightmares, yawning; sometimes: the activation of the symptoms of psychosis.

Neurological status: very often - dizziness, tremor, headache, myoclonus;
often - delirium, speech disorders, paresthesia, muscle weakness, increased muscle tone;
sometimes - cramps, ataxia; very rarely - changes in the electroencephalogram, increase in body temperature.

AnTikhoninergic effects: very often - dry mouth, excessive sweating, constipation, disruption of accommodation, blurred vision ("vein before the eyes "), urination disorders, often - hot flashes, mydriasis, very rarely - glaucoma, urinary retention.

From the cardiovascular system: often - sinus tachycardia, palpitations, orthostatic hypotension, clinically insignificant changes on the ECG
(e.g., an interval ST or T wave) in patients without a pathology of the heart; sometimes - arrhythmias, increased blood pressure; very rarely - violations of intracardiac conduction (for example, the expansion of the complex QRS, lengthening the interval QT, interval changes PQ, bundle branch blockade, bi-directional spindle-shaped ventricular tachycardia ("torsade de points"), especially in patients with hypokalemia).

From the gastrointestinal tract (FTOT): very often - nausea; often - vomiting, abdominal discomfort, diarrhea, anorexia.

From the side of the liver: often - increased levels of transaminases; very rarely, hepatitis with or without jaundice.

Dermatological reactions: often - allergic skin reactions (rash, urticaria), photosensitization, pruritus; very rarely - swelling (local or general), hair loss.

From the endocrine system and metabolism: very often - weight gain, libido and potency disorders; often - galactorrhea, enlarged mammary glands; very rarely - the syndrome of inadequate secretion of antidiuretic hormone.

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

On the part of the hematopoiesis system: very rarely - leukopenia, agranulocytosis, eosinophilia, thrombocytopenia, purpura.

From the sense organs: often - the violation of taste sensations, noise in the ears.

The withdrawal syndrome: after sudden withdrawal or rapid dose reduction Anafranil often have the following symptoms: nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, irritability, anxiety.

Overdose:

Symptoms that develop with an overdose of Anafranil are similar to those described in an overdose of other tricyclic antesidstressorat. The main complications are heart disorders and neurological disorders.

In children, the occasional intake of any dose of the drug inside should be regarded as a very serious and fatal event.

Symptoms

Symptoms usually PAppear within 4 hours after taking the drug and reach maximum severity after 24 hours. Due to delayed absorption (anticholinergthe effect of the drug), a long half-life andPatoeMr.therial recirculation of the active substance, the period of time during which the patient remains in the "risk zone" is 4-6 days.

The following symptoms may occur.

From the side of tseMr.tropicMr.th nervous system:
drowsiness, stupor, coma, ataxia, becalmness, agitation, strengtheningeflexes, rigidity of muscles, choreoathetoidse movement, convulsions. In addition, there may be manifestations fromepfromninovoth syndrome (increased tbody temperature, myoclonus, delirium, coma).

From the side of thedVascular system: marked decrease in blood pressure, tachycardia, lengthening QT-Interval, arrhythmias (including "torsade de points") violations of intracardiac conduction, shock, heart failure, in very rare cases - cardiac arrest.
Besides, possible respiratory depression, cyanosis, vomiting, fever, mydriasis, sweating, oliguria or anuria.

Treatment

There is no specific antidote, treatment is, in the main, symptomatic and supportive. If you suspect an overdose of Anafranil, especially in children, the patient should be hospitalized and monitored carefully for at least 72 hours.
If the patient is conscious, promptly wash the stomach or induce vomiting. If the patient is unconscious, before starting the gastric lavage, intubation of the trachea should be performed using a tube with a cuff to prevent aspiration; Vomiting in this case does not cause. These measures are recommended to be carried out even if 12 hours or more have passed since the overdose, since the anticholinergic action of Anafranil may slow down the emptying of the stomach. To reduce the absorption of the drug, it is useful to use activated carbon.

Treatment is based on the use of modern intensive care
permanent monitoring of cardiac function, gas composition and blood electrolytes, as well as the application, if necessary, of such urgent measures as anticonvulsant therapy, artificial ventilation and resuscitation methods. Since the reports that physostigmine can cause severe bradycardia, asystole and seizures, it is not recommended to use this drug to treat an overdose of Anafranil.
Hemodialysis and peritoneal dialysis are not effective,since clomipramine concentrations in the blood plasma are low.

Interaction:

Pharmatouniquelytotype of interaction

Blockers of adrenergic neuronal transmission.

Anaphranil can reduce or completely eliminate the antihypertensive effects of guanethidine, betanidine, reserpine, clonidine and athemethyldopa. Therefore, in cases when simultaneous administration of Anafranil requires the treatment of hypertension, other drugs should be used (eg, vasodilators or beta-blockers).

AnticholiMr.Ergic means. Tricyclic antidepressants can potentiate the action of anticholinergics (eg, phenothiazines, antiparkinsonics, atropine, biperiden, antihistamines) on the organ of vision, the central nervous system, the intestine and the bladder.

Means that depress the central nervous system. Tricyclic antidepressants can enhance the effects of alcohol and other drugs that have a depressing effect on the central nervous system (eg, barbiturates, benzodiazepines, or anesthesia drugs).

Inhibitors MAABOUT. He should be prescribed Anafranil for at least2 weeks after the abolition of MAO inhibitors because of the risk of developing such severe symptoms and conditions as hypertensive crisis, fever, as well as symptoms of serotonin syndrome: myoclomaMr.mustache, agitation, convulsions, delirium and coma. TThe same rule should be followed if the MAO inhibitor is given after the previous oneeAnafranil. In either of these cases Mr.Primary doses of Anafranil or MAO inhibitors should be low, they should be PTo overestimate gradually, under the constant control of effects of a preparation.

The existing experience shows that Anafranil can be prescribed not earlier than in 24 hours Pdonkey abouttmeMr.s andMr.bendthe resultMAO-Atnogo activitiesart.vija, takix as moxobemide. But, if the MAO-A inhibitor of reversible action is appointed after canceling Anafranil, the duration of the break should be at least 2 weeks.

Selective serotonin reuptake inhibitors.

The combined use of anaphranil with these agents may lead to an increased effect on the serotonin system.

Serotonergic agents. With simultaneous use of Anafranil with selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors, tricyclic antidepressants and lithium preparations, the development of serotonin syndrome with symptoms such as fever, myoclonus, agitation, convulsions, delirium and coma is possible. If it is necessary to prescribe fluoxetine, it is recommended to take a two-three-week break between the use of Anafranil and fluoxetine - to complete the use of fluoxetine 2-3 weeks before the initiation of Anaphranil therapy or to appoint fluoxetine 2-3 weeks after the end of Anafranil treatment.

Sympathomymethnictoth means.

Anaphranil can strengthen the effect on the cardio-vascular system of adrenaline, norepinephrine, isoprenaline, ephedrine and phenylephrine (even when these substances are part of local anesthetics).
Pharmacotoinethictotype of interaction

The active substance of the drug Anafranil - clomipramine - basically it is displayed in the form of metabololites. The main pathway of metabolism is demethylation to the active metabolite N-desmethylclomipramine, followed by hydroxylation and conjugation N-desmethylclomipramine with clomipramine. Several cytochrome P450 isoforms participate in the demethylation, mainly CYP3A4, CYP2C19 and CYP1A2. Elimination of both active components is carried out by hydroxylation, which is catalyzed CYP2D6. Joint administration with isoform inhibitors CYP2D6 may lead to an increase
concentrations of both active components to threefold in individuals with the phenotype of the rapid metabolizer of debrisoquine/sparteine. At the same time, in these patients, the metabolism decreases to a level characteristic for persons with the phenotype of a weak metabolizer. It is assumed that the joint administration with isoform inhibitors CYP1A2, CYP2C19 and CYP3A4 can lead to an increase in the concentration of clomipramine and a decrease in the concentration N-de-methyl-clomipramine.

MAO inhibitors (for example moclobemide) are contraindicated in taking clomipamine, since in vivo they are potent inhibitors CYP2D6.

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

Selective serotonin reuptake inhibitors (such as fluoxetine,
paroxetine or sertraline) inhibit CYP2D6, other preparations of the said group
(eg fluvoxamine) also inhibit CYP1A2, CYP2C19, which can lead to increase in the concentration of clomipramine in plasma and the development of appropriate
undesirable effects. A 4-fold increase in the equilibrium
concentrations of clomipramine when taken together with fluvoxamine (concentration
N-desmethylclomipramine was reduced 2-fold).

- Joint use of neuroleptics (for example,Mr.otiazines) can lead to an increase in plasma concentrations of tricyclic antidepressants, a decrease in the convulsive threshold and the occurrence of seizures. Combination with thioridazine may lead to the development of severe cardiac arrhythmiasumma.

- Joint application with histamine blocker (H2)receptors with cimetidine (which is an inhibitor of certain cytochrome P450 isoforms, including CYP2D6 and CYP3A4) can lead to an increase in plasma concentrations
tricyclic antidepressants, in connection with which a reduction in the dose of the latter is required.

- There is no evidence to support the interaction between anaphranil (at a dose of 25 mg per day) and oral contraceptives (15 or 30 μg ethinylestradiol per day) with a constant intake of the latter.There is no evidence that estrogens are inhibitors CYP2D6 - mainstream enzyme, of the participating at elimination of clomipramine, so there is no reason expect their interaction.

Although, with simultaneous application of tricyclic antidepressant imipramine and estrogens in high doses (50 μg per day), in some cases, reported worsening of side effects and increased therapeutic effect
antidepressant. It is not known whether these data are significant in relation to
simultaneous use of clomipramine and estrogens in low doses. When
combined use of tricyclic antidepressants and estrogens in high
doses (50 mcg per day), it is recommended to monitor the therapeutic effect
antidepressants, and, if necessary, correction of the dosing regimen.

Methylphenidate (Ritalin) can help increase the concentration
tricyclic antidepressants, possibly due to the suppression of their metabolism. When
joint use of these drugs may increase the concentration of
tricyclic antidepressants in blood plasma, it may be necessary
reduce the dose of the latter.

Some tricyclic antidepressants may increase anticoagulant
the action of coumarins (for example, warfarin), possibly by inhibiting them
metabolism (CYP2C9). There is no evidence to prove the ability of clomipromine
inhibit the metabolism of anticoagulants (warfarin). Nevertheless, with
use of this class of drugs is recommended monitoring
concentration of prothrombin in plasma.

Joint reception of Anafranil with drugs - inducers of cytochrome P450, especially CYP3A4, CYP2C19 and / or CYP1A2 can lead to increased metabolism and reduce the effectiveness of Anafranil.

Joint reception Anafranil with drugs - inducers CYP3A and CYP2C, such as rifampicin or anticonvulsant drugs (for example
barbiturates, carbamazepine, phenobarbital and phenytoin), can lead to a decrease
concentration of clomipramine in plasma.

Known inductors CYP1A2 (e.g., nicotine anddOther components of the cigarette
smoke) reduce the concentration of tricyclic antidepressants in blood plasma.
The equilibrium concentration of clomipramine in cigarette smoking people is 2 times lower than that
in non-smokers (the concentration of N-desmethylclomipramine did not change).

Clomipramine, as in vivo, and in vitro (Ki=2.2 microM), inhibits activity CYP2D6 (oxidation of sparteine). In this way, clomipramine can increase concentrations of concomitantly used drugs, metabolized mainly with participation CYP2D6, in individuals with a phenotype of a strong metabolizer.

Special instructions:

When Anaphranil is used in doses exceeding the average therapeutic dose, or if the clomipramine concentration in the plasma exceeds the average therapeutic level, there is a risk of lengthening QTc-interval and occurrence of bidirectional spindle-shaped ventricular tachycardia ("torsade de points") This is observed in the case of co-administration with selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors.Therefore, it is necessary to avoid the simultaneous administration of clomipramine and the drugs that cause its cumulation, and it is also necessary to avoid joint intake with drugs that cause lengthening QT-Interval. It has been established that hypokalemia is a risk factor for lengthening QT-interval and occurrence of bidirectional spindle-shaped ventricular tachycardia ("torsade de points"). Therefore, hypokalemia should be eliminated before therapy with anaphranil.
Because of the risk of developing serotonin toxicity and lengthening the interval QT should be
adhere to the recommended dosage and carefully increase the dose in a joint appointment with drugs that extend the interval QT, and serotonergic drugs.

With the simultaneous use of anaphranil with serotonergic drugs, such
such as selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, tricyclic antidepressants or lithium preparations, possibly the development of serotonin syndrome with symptoms such as fever, myoclonus, agitation, convulsions, delirium and coma. If it is necessary to administer fluoxetine, it is recommended to take a two-three-week break between the use of anaphranil and fluoxetine (see section "Interaction with other drugs", serotonergic drugs).
In many patients with panic disorders at the beginning of treatment with anaphranil
anxiety increases. This paradoxical increase in anxiety is most pronounced in the first days of therapy and usually subsides for two weeks.

In patients with schizophrenia receiving tricyclic antidepressants, sometimes the activation of psychosis is noted.

In patients with liver disease, periodic monitoring of hepatic enzyme activity is recommended.

Anaphranil, as well as other tricyclic antidepressants, is prescribed in combination with electroconvulsive therapy only under the condition of careful medical supervision.
Depression is characterized by the risk of suicidal actions, which can
persist until a reliable remission is achieved. In patients with depression, both in adults and in children, depression and / or suicidal behavior or other psychiatric symptoms may increase, regardless of whether they receive antidepressant therapy 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 illnessesand.

All patients taking Anafranil for any of the indications should be examined for worsening clinical picture, suicidal behavior and other psychiatric symptoms, especially in the initial phase of therapy or when changing the dose of the drug.Such patients should consider the possibility of changing the regimen of therapy, including the possible withdrawal of the drug, especially if such changes are pronounced, suddenly or not observed in the patient initially.

Families and guardians of patients (both children and adults) who take antidepressant medications for psychiatric or non-psychiatric reasons should be warned about the need to monitor patients because of the risk of other psychiatric symptoms, including suicidal behavior, and immediately report such symptoms to the treating doctors.

When prescribing for Anafranil, the minimum number of tablets should be indicated to reduce the risk of overdose. In this case, an adequate treatment regimen should be observed. There is evidence suggesting that with the use of Anafranil, there are fewer deaths due to an overdose than with the use of other tricyclic antidepressants.

Before conducting general or local anesthesia, an anesthesiologist should be warned thatcentnersThe patient takes Anafranil.

An increase in the incidence of dental caries during prolonged treatment has been reported
tricyclic antidepressants. Therefore, in the case of prolonged therapy Anafranil recommended regular examination of the patient by the dentist.

The use of diuretics can lead to the development of hypokalemia, which increases the risk of lengthening QT-interval and occurrence of bidirectional spindle-shaped ventricular tachycardia ("torsade de points"). Before starting therapy Anafranyl should be corrected hypokalemia.

An abrupt withdrawal of Anafranil should be avoided, as this may lead to side effects
reactions. If a decision is made to discontinue treatment, the drug should be withdrawn gradually, as quickly as the clinical situation permits. It should be taken into account that the abrupt withdrawal of the drug may be accompanied by the development of certain fromof symptoms.

Anafranil, coated tablets, contains lactose and sucrose. Patients with rare hereditary diseases, such as intolerance to galactose and fructose, severe lactase deficiency, sucrose-isomaltase deficiency or malabsorption of glucose-galactose, do not take tablet coated Anafranil tablets.

Effect on the ability to drive transp. cf.and fur:Patients who experience drowsiness and other abnormalities from the CNS, including blurred vision, should not drive a car, operate machinery, or engage in other activities that require increased attention and quick response.

Form release / dosage:

The coated tablets are 25 mg.

Packaging:

For 10 tablets in a blister of PVC / PE / PVDC and foil aluminum.

2 or 3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

In the original packaging at a temperature not exceeding 25 ° CFROM.

The drug should be stored out of the reach of children.

Shelf life:

5 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011860 / 01

Date of registration:30.09.2011 / 11.09.2012

Expiration Date:Unlimited

The owner of the registration certificate:Novartis Pharma, LLC Novartis Pharma, LLC Russia

Manufacturer: & nbsp

Novartis Pharma, LLC Russia

Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC

Information update date: & nbsp01.09.2017

Illustrated instructions

Instructions

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