Anafranil, 30 pcs., 25 mg, film-coated tablets

Anafranil tablet p/o 25 mg N30 (Novartis)

It is known that tricyclic antidepressants reduce the threshold for 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 occurrence of convulsive syndrome, for example, brain damage of any etiology, while using antipsychotic drugs, during the period of withdrawal from alcohol or withdrawal from drugs that have anticonvulsant properties (for example, benzodiazepines). It is believed that the occurrence of seizures while taking Anafranil depends on the dose of the drug. In this regard, you should not exceed the recommended daily dose of Anafranil. Anafranil should be prescribed with extreme caution to patients with cardiovascular diseases, especially cardiovascular failure, intracardiac conduction disorders (for example, AV block I-III degrees) or arrhythmias. In such patients, as well as in elderly patients, it is necessary to regularly monitor heart function and ECG. Before starting Anafranil therapy, it is recommended to measure blood pressure, since patients with orthostatic hypotension or lability of the cardiovascular system may experience a sharp decrease in blood pressure. Because the drug has anticholinergic properties, it should be used with extreme caution in patients with a history of increased intraocular pressure, angle-closure glaucoma, or urinary retention (for example, due to prostate disease). Due to the anticholinergic action characteristic of tricyclic antidepressants, there may be a decrease in tear production and accumulation of mucous secretion, which can lead to damage to the corneal epithelium in patients using contact lenses. Caution is necessary when treating patients with severe liver disease with tricyclic antidepressants, as well as in patients with tumors of the adrenal medulla (for example, pheochromocytoma, neuroblastoma), since in this case these drugs can provoke the development of a hypertensive crisis. It is known that patients with cyclic affective disorders taking tricyclic antidepressants may develop manic or hypomanic states during the depressive phase. In such cases, it may be necessary to reduce the dose of Anafranil or discontinue it and prescribe antipsychotic therapy. After relief of these conditions, if indicated, treatment with Anafranil in low doses can be resumed. In predisposed patients and elderly patients, tricyclic antidepressants can provoke the development of drug-induced delirious psychoses, mainly at night. After discontinuation of the drug, these disorders disappear within a few days.

Anafranil®

Contraindicated drug interactions

MAO inhibitors (linezolid, furazolidone, etc.)

Clomipramine should not be used for at least 2 weeks after discontinuation of MAO inhibitors due to the risk of developing conditions such as hypertensive crisis, fever, and symptoms of serotonin syndrome: myoclonus, agitation, seizures, delirium and coma. The same rule should be followed if a MAO inhibitor is used after previous treatment with clomipramine. In any of these cases, the initial doses of clomipramine or MAO inhibitors should be low and increased gradually, with constant monitoring of the drug's effects.

Current experience shows that clomipramine can be prescribed no earlier than 24 hours after discontinuation of reversible MAO A inhibitors such as moclobemide. But if a reversible MAO A inhibitor is used after discontinuation of the drug Anafranil®, the duration of the break should be at least 2 weeks.

Linezolid

(which is a non-selective MAO inhibitor of reversible action) should not be used simultaneously with clomipramine.

Medicines not recommended for simultaneous use

Antiarrhythmic drugs (eg, quinidine and propafenone)

should not be used simultaneously with tricyclic antidepressants, as they are potent inhibitors of the CYP2D6 isoenzyme.

Diuretic drugs.

Diuretics may cause hypokalemia, which in turn increases the risk of QTc prolongation and varicose veins. Correction of hypokalemia should be carried out before starting drug therapy. It may be necessary to correct other fluid and electrolyte imbalances, such as hypomagnesemia, before starting drug therapy.

Selective serotonin reuptake inhibitors (such as fluoxetine, paroxetine, or sertraline)

inhibit the CYP2D6 isoenzyme, other drugs of this group (for example, fluvoxamine) also inhibit the CYP1A2, CYP2C19 isoenzymes, which can lead to an increase in the concentration of clomipramine in the blood plasma and the development of corresponding undesirable effects. A 4-fold increase in the equilibrium concentration of clomipramine was observed when taken simultaneously with fluvoxamine (the concentration of N-desmethylclomipramine decreased by 2 times).

When clomipramine is used concomitantly with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors

,
tricyclic antidepressants and lithium preparations
, the development of serotonin syndrome is possible.

If necessary, use fluoxetine

, it is recommended to take a two to three week break between the use of clomipramine and fluoxetine - stop using fluoxetine 2-3 weeks before starting clomipramine therapy or start fluoxetine therapy 2-3 weeks after finishing clomipramine treatment.

Concomitant use of Anafranil® with selective serotonin reuptake inhibitors may lead to increased effects on the serotonin system.

Possible drug interactions

Drug interactions that enhance the therapeutic effects of Anafranil®

Concomitant use with inhibitors of the CYP2D6 isoenzyme

may result in up to a three-fold increase in concentrations of both active components in individuals with the rapid debrisoquine/sparteine ​​metabolizer phenotype. At the same time, in these patients, metabolism decreases to a level characteristic of individuals with a poor metabolizer phenotype.

It is assumed that simultaneous use with inhibitors of the isoenzymes CYP1A2, CYP2C19 and CYP3A4

may lead to an increase in the concentration of clomipramine and a decrease in the concentration of N-desmethylclomipramine, which generally does not affect the pharmacological parameters.

When using the drug Anafranil® simultaneously with the antifungal drug terbinafine

(a potent inhibitor of the CYP2D6 isoenzyme) in oral form may increase the exposure and accumulation of clomipramine, as well as its N-demethylated metabolite. When clomipramine is used together with terbinafine, a dose adjustment of clomipramine is required.

Concomitant use with the H1-histamine receptor blocker cimetidine

(which is an inhibitor of some cytochrome P450 isoenzymes, including CYP2D6 and CYP3A4 isoenzymes) may lead to an increase in plasma concentrations of tricyclic antidepressants, which requires a reduction in the dose of the latter.

There is no evidence of interaction between clomipramine (at a dose of 25 mg per day) and oral contraceptives

(15 or 30 mcg ethinyl estradiol per day) with constant use of the latter. There is no evidence that estrogens are inhibitors of the CYP2D6 isoenzyme, the main isoenzyme involved in the elimination of clomipramine, so there is no reason to expect their interaction. Although, with the simultaneous use of the tricyclic antidepressant imipramine and estrogens in high doses (50 mcg per day), in some cases, worsening side effects and an increase in the therapeutic effect of the antidepressant have been reported. It is unknown whether these data are significant with respect to the concomitant use of clomipramine and low-dose estrogens. With the simultaneous use of tricyclic antidepressants and estrogens in high doses (50 mcg per day), it is recommended to monitor the therapeutic effect of antidepressants and, if necessary, adjust the dosage regimen.

Concomitant use of antipsychotics

(for example, phenothiazine derivatives) may lead to increased plasma concentrations of tricyclic antidepressants, a decrease in the seizure threshold and the occurrence of seizures.

Combination with thioridazine

may lead to the development of severe heart rhythm disturbances.

Methylphenidate

may increase plasma concentrations of tricyclic antidepressants, possibly by inhibiting their metabolism. In this case, it may be necessary to reduce the dose of the latter.

With simultaneous use of valproic acid

and clomipramine may inhibit the CYP2C isoenzyme and/or uridyl diphosphate glucuronyl transferase, which may lead to increased plasma concentrations of clomipramine and desmethylclomipramine.

Drug interactions that reduce the therapeutic effects of Anafranil®

Concomitant use of clomipramine with inducers of CYP3A and CYP2C isoenzymes

, such as
rifampicin
or anticonvulsants (for example,
barbiturates (phenobarbital), carbamazepine and phenytoin
, which are inducers of cytochrome P450 isoenzymes, namely CYP3A4 CYP2C19), can lead to an acceleration of metabolism, a decrease in the concentration of clomipramine in the blood plasma and a decrease in the effectiveness of the drug Anafranil®.

Inducers of the CYP1A2 isoenzyme

(for example, nicotine/other components of cigarette smoke) reduce the concentrations of drugs with a tricyclic structure in the blood plasma. The steady-state concentration of clomipramine in patients who smoke cigarettes is 2 times lower than that in non-smokers (the concentration of N-desmethylclomipramine did not change).

With simultaneous use of ion exchange resins

(for example,
cholestyramine
or
colestipol
), a decrease in the concentration of clomipramine in the blood serum may occur. It is recommended to use clomipramine at least 2 hours before or 4-6 hours after applying resins.

St. John's wort

may lead to decreased plasma concentrations of clomipramine when used concomitantly.

Drug interactions that do not affect Anafranil®

Tricyclic antidepressants can potentiate the effect of drugs that have an anticholinergic effect (for example, phenothiazine derivatives, antiparkinsonian drugs, atropine, biperiden, H1-histamine receptor blockers

) on the organ of vision, central nervous system, intestines and bladder. In addition, with the simultaneous use of the above drugs, there is a risk of developing hyperthermia.

Clomipramine may reduce or completely eliminate the antihypertensive effects of guanethidine, betanidine, reserpine, clonidine and methyldopa

. Therefore, in cases where treatment of arterial hypertension is required simultaneously with clomipramine, drugs of other classes (for example, vasodilators or beta-blockers) should be used.

Tricyclic antidepressants may enhance the effects of ethanol

and other drugs that have a depressant effect on the central nervous system (for example,
barbiturates, benzodiazepines or anesthetics
).

Clomipramine may increase the effects of epinephrine

on the cardiovascular system,
norepinephrine, isoprenaline, ephedrine and phenylephrine
(including when these substances are part of local anesthetics).

Some tricyclic antidepressants may enhance the anticoagulant effect of coumarin derivatives

(for example,
warfarin
), possibly by inhibiting their metabolism (CYP2C9 isoenzyme). There is no data proving the ability of clomipromine to inhibit the metabolism of anticoagulants (warfarin). However, when using this class of drugs, monitoring the concentration of prothrombin in the blood plasma is recommended.

In addition, clomipramine is in vitro

and
in vivo
inhibitor of the activity of the CYP2D6 isoenzyme (sparteine ​​oxidation). Thus, clomipramine may increase the concentrations of concomitantly used drugs that are metabolized primarily through the CYP2D6 isoenzyme.

Incompatibility

: solution of Anafranil® with
diclofenac
.

Composition and release form

10 pcs in blister; There are 2 or 3 blisters in a cardboard pack.

in ampoules of 2 ml; There are 10 ampoules in a cardboard pack.

Anafranil, 30 pcs., 25 mg, film-coated tablets

Hypokalemia should be corrected before starting therapy.

The dosage regimen and method of administration of the drug are determined individually, taking into account the patient’s condition. The goal of treatment is to achieve optimal effect by using the lowest possible doses of the drug and increasing them carefully. Particular caution should be exercised when increasing doses in elderly patients and adolescents, who are generally more sensitive to Anafranil® than patients in intermediate age groups.

Inside, intravenously (in the form of infusions), intramuscularly.

Depression, obsessive-compulsive syndromes and phobias

The initial daily dose is 75 mg; prescribe the drug Anafranil® 25 mg 2-3 times a day or Anafranil® SR 75 mg 1 time 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 is reached. In severe cases, the daily dose can be increased to a maximum of 250 mg. After improvement is achieved, the patient is transferred to a maintenance dose of the drug of 50–100 mg (2–4 tablets of Anafranil® or 1 tablet of Anafranil® CP).

Panic attacks, agoraphobia

The initial dose of Anafranil® is 10 mg/day. Then, depending on the tolerability of the drug Anafranil®, its dose is increased until the desired effect is achieved. The daily dose of Anafranil® varies greatly and can range from 25 to 100 mg. If necessary, the dose can be increased to 150 mg/day. It is recommended not to stop treatment for at least 6 months, slowly reducing the maintenance dose of the drug during this time.

Cataplexy associated with 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 analgesics and the possibility of reducing the use of the latter should be taken into account.

Elderly patients.

The initial dose is 10 mg/day. Then gradually, over about 10 days, the daily dose of the drug is increased to the optimal level, which is 30–50 mg.

Children and teenagers

Obsessive-compulsive syndromes

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 of either 100 mg or calculated at 3 mg/kg is reached, whichever is lower. Over the next few weeks, the dose continues to be gradually increased until a daily dose of either 200 mg or calculated at 3 mg/kg is reached, 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 over 12 years old - 25–75 mg. The use of higher doses is indicated for those patients who have no clinical effect after 1 week of treatment. Usually the entire daily dose of the drug is prescribed in one dose after dinner, but in cases where involuntary urination occurs in the early hours of the night, part of the dose of Anafranil® is prescribed earlier - at 16:00. After achieving the desired effect, treatment should be continued for 1-3 months, gradually reducing the dose of Anafranil®.

Injection

IM injections

Treatment begins with the introduction of 25–50 mg (contents of 1–2 amp.), then daily increase the dose by 25 mg (1 amp.) until a daily dose of 100–150 mg (4–6 amp.) is reached. After improvement is noted, the number of injections is gradually reduced, replacing them with maintenance therapy with oral forms of the drug.

IV infusion

Treatment begins with intravenous drip administration of 50–75 mg (contents of 2–3 amp.) 1 time per day. To prepare the infusion solution, use 250–500 ml of isotonic sodium chloride solution or glucose solution; the duration of the infusion is 1.5–3 hours. During the infusion, careful monitoring of the patient is necessary for the timely detection of possible adverse reactions. Particular attention should be paid to blood pressure control, because Orthostatic hypotension may develop. When a clear improvement is achieved, Anafranil® is administered intravenously for another 3–5 days. Then, to maintain the achieved effect, they switch to taking the drug orally; 2 tables 25 mg are usually equivalent to 1 amp. Anafranil® drug containing 25 mg. In order to gradually transition from infusion therapy to maintenance oral administration of the drug, you can first transfer the patient to IM administration.

The maximum therapeutic dose of the drug is 150 mg/day.