Fevarin

General characteristics. Structure:

Active agent: fluvoksamina maleate of 50 or 100 mg

Excipients: Mannitolum — 152 or 303 mg; starch corn — 40 or 80 mg; starch prezhelatinizirovanny — 6 or 12 mg; sodium of a stearil fumarates — 1,8 or 3,5 mg; silicon dioxide colloid anhydrous — 0,8 or 1,5 mg  

Cover: a gipromelloza — 4,1 or 5,6 mg; macrogoal of 6000 — 1,5 or 2 mg; talc — 0,3 or 0,4 mg; titanium dioxide (E171) — 1,5 or 2,1 mg.

Pharmacological properties:

Pharmacodynamics. Selectively inhibits the return serotonin reuptake by neurons of a brain and it is characterized by the minimum influence on noradrenergichesky transfer. Феварин® the m - cholinergic, dofaminergichesky or serotonergic receptors has not expressed ability to communicate with alpha and beta and adrenergic, gistaminergichesky.

Pharmacokinetics. At intake it is completely soaked up from a GIT. Cmax is reached in 3–8 h, equilibrium concentration — in 10–14 days. Absolute bioavailability makes 53% after primary metabolism in a liver. The concomitant use of Fevarina® with food does not influence pharmacokinetics.
Linkng with proteins of a blood plasma — about 80%. Distribution volume — 25 l/kg.
Metabolism of Fevarina® happens mainly in a liver. Though the isoenzyme 2D6 of P450 cytochrome is the basic in metabolism of a fluvoksamin, concentration of drug in a blood plasma at persons with reduced function of this isoenzyme is not much higher, than at persons with normal metabolism. The average T1/2 from a blood plasma making for a single dose of 13-15 h increases a little at multiple dose (17–22 h), and equilibrium concentration in a blood plasma is, as a rule, reached in 10–14 days.

Феварин® is exposed to biotransformation in a liver (mainly by oxidizing demethylation) at least to 9 metabolites which are removed through kidneys. 2 main metabolites have insignificant pharmacological activity. Other metabolites probably pharmacological are inactive. Fluvoksamin considerably inhibits P450 1A2 cytochrome, moderately inhibits tsitokhroma of P450 2C and P450 3A4, is insignificant — P450 2D6 cytochrome.

The pharmacokinetics of a fluvoksamin is identical at healthy people, elderly and patients with a renal failure. Metabolism is reduced at patients with liver diseases.
The established concentration of a fluvoksamin in plasma at children at the age of 6–11 years — are twice higher, than at teenagers (12–17 years). Concentration of drug in a blood plasma of teenagers are similar to those at adults.

Indications to use:

- depressions of various genesis;
- obsessivno-compulsive frustration.

Route of administration and doses:

Inside, without chewing and washing down with a small amount of water.

Depressions. The recommended starting dose makes 50 or 100 mg (once, in the evening). Gradual increase in a starting dose to level effective is recommended. The effective daily dose making usually 100 mg is selected individually, depending on reaction of the patient to treatment. The daily dose can reach 300 mg. Daily doses over 150 mg should be distributed on several receptions. According to official WHO recommendations, treatment by antidepressants should be continued, at least, within 6 months of remission after a depressive episode. For prevention of a recurrence of a depression about 100 mg of Fevarina® are recommended to accept once a day.

Obsessivno-kompulsivnye frustration. It is recommended to begin with a dose 50 mg of Fevarina® a day within 3–4 days. The effective daily dose makes, as a rule, from 100 to 300 mg. Doses should be raised gradually to achievement of an effective daily dose which should not exceed 300 mg at adults. Doses to 150 mg can be accepted in the form of one-time, it is desirable in the evening. Daily doses over 150 mg are recommended to be distributed on 2 or 3 receptions.

Doses for children are more senior than 8 years and teenagers: initial — 25 mg/days on 1 reception, supporting — 50–200 mg/days. The daily dose should not exceed 200 mg. Daily doses over 100 mg are recommended to be distributed on 2 or 3 receptions.

At the good answer to drug treatment can be continued in individually picked up daily dose. If improvement is not reached in 10 weeks of treatment, флувоксамин it is necessary to cancel. Still system researches which could answer a question of how treatment fluvoksaminy can long be carried out were not organized, however obsessivno-compulsive frustration have chronic character and therefore it is possible to consider expedient extension of treatment of Fevarinom® over 10 weeks at the patients who well answered this drug. Selection of the minimum effective maintenance dose has to be carried out with care in an individual order. Some clinical physicians recommend carrying out the accompanying psychotherapy at the patients who well answered pharmacotherapy.

Treatment of the patients having a liver or renal failure should be begun with the smallest doses under strict medical control.

Due to the lack of clinical experience of Fevarin® it is not recommended to apply to treatment of depressions at children.

Features of use:

During treatment drug does not recommend alcohol intake.

The patients having a depression have, as a rule, a high probability of attempt of a suicide which can remain before achievement of sufficient remission. Such patients have to be under observation.

Treatment of the patients having a liver or renal failure should be begun with minimum effective doses of Fevarina® under strict medical control. In rare instances treatment of Fevarinom® can lead to the increase in level of hepatic transaminases most of which often is followed by the corresponding clinical symptoms. In these cases of Fevarin® it has to be cancelled.

Control of glucose level in blood, especially at early stages of treatment can be broken. Correction of a dosage of anti-diabetic drugs can be required.

It is necessary to show care at purpose of drug the patient with spasms in the anamnesis. It is necessary to avoid purpose of Fevarina® the patient with unstable epilepsy, and patients with stable epilepsy have to be under strict medical control. Treatment of Fevarinom® has to be stopped in case of development of epileptic seizures or increase in their frequency.

Exceptional cases of development of a serotonergic syndrome or state, similar to a malignant antipsychotic syndrome which can be connected with reception of a fluvoksamin, in a combination with other serotonergic antidepressants and neuroleptics are described. As these syndromes can lead to potentially life-threatening states, the shown hyperthermia, muscle tension, a myoclonus, lability of an autonomous nervous system with possible fast changings of the vital parameters, changes of the mental status, including an acrimony, agitation, confusion of consciousness, delirious frustration and a coma — treatment fluvoksaminy has to be stopped. If necessary it is necessary to begin the corresponding treatment.

As well as at use of other selective inhibitors of the return serotonin reuptake, in rare instances against the background of reception of a fluvoksamin emergence of a hyponatremia which is exposed to involution after drug withdrawal is possible. Some cases were caused by a syndrome of insufficient secretion of antidiuretic hormone. Generally these cases were observed at elderly patients.

There are messages on such intradermal hemorrhages as an ecchymoma and a purpura, and also on the hemorrhagic manifestations (for example gastrointestinal bleeding) observed at use of selective inhibitors of the return serotonin reuptake. It is necessary to show care at purpose of these HP at the elderly patients and patients who are at the same time receiving the drugs operating on platelet function (atypical antipsychotic means and fenotiazina, many tricyclic antidepressants, aspirin, NPVS) or the drugs increasing risk of development of bleedings and also at patients with bleedings in the anamnesis and inclined to bleedings (for example at patients with thrombocytopenia).

At a combination therapy with fluvoksaminy concentration of a terfenadin, astemizol or tsizaprid in a blood plasma can increase, increasing risk of lengthening of an interval of QT. Therefore флувоксамин it is not necessary to appoint with these drugs.

The data obtained at treatment of patients of advanced age and younger patients confirm lack of clinically significant distinctions between the daily doses which were usually applied at them. Nevertheless, increase in doses of drug at elderly patients has to be carried out always more slowly and with бóльшей care. Феварин® can lead to insignificant decrease in ChSS (on 2–6 beats per minute).

Due to the lack of clinical experience of Fevarin® it is not recommended to apply to treatment of depressions at children.

Феварин®, appointed to healthy volunteers in doses to 150 mg did not influence or exerted insignificant impact on ability to driving of the car or to control of cars. At the same time there are messages on the drowsiness noted during treatment by drug. In this regard it is recommended to be careful before final definition of the individual answer to drug.

Side effects:

The most often observed symptom connected using Fevarina® is the nausea which sometimes is followed by vomiting. This by-effect, as a rule, disappears in the first 2 weeks of treatment.

Some side effects observed when carrying out clinical tests often were connected with depression symptoms, but not with the carried-out treatment of Fevarinom®.

The general: often (1–10%) — an adynamy, a headache, an indisposition.

From cardiovascular system: often (1–10%) — heartbeat, tachycardia; sometimes (less than 1%) — postural hypotension.

From a GIT: often (1–10%) — an abdominal pain, anorexia, a lock, diarrhea, dryness in a mouth, dyspepsia; seldom (less than 0,1%) — an abnormal liver function (increase in level of hepatic transaminases).

From TsNS: often (1–10%) — nervousness, alarm, agitation, dizziness, sleeplessness or drowsiness, a tremor; sometimes (less than 1%) — an ataxy, confusion of consciousness, extrapyramidal disturbances, hallucinations; seldom (less than 0,1%) — spasms, a maniacal syndrome.

From skin: often (1–10%) — perspiration; sometimes (less than 1%) — skin reactions of hypersensitivity (rash, an itch, a Quincke's disease); seldom (less than 0,1%) — a photosensitization.

From skeletal and muscular system: sometimes (less than 1%) — an arthralgia, a mialgiya.

From a reproductive system: sometimes (less than 1%) — the slowed-down ejaculation; seldom (less than 0,1%) — a galactorrhoea.

Others: seldom (less than 0,1%) — change of body weight; serotonergic syndrome, state, similar to an antipsychotic malignant syndrome, hyponatremia and syndrome of insufficient secretion of antidiuretic hormone; very seldom — paresthesias, an anorgazmiya and a food faddism.

At the termination of reception of a fluvoksamin development of symptoms of cancellation — dizziness, paresthesias, a headache, nausea, alarm is possible (the majority of symptoms are expressed poorly and are stopped independently). At drug withdrawal the gradual dose decline is recommended.

Hemorrhagic manifestations — ecchymomas, a purpura, gastrointestinal bleedings.

Interaction with other medicines:

Феварин® it is impossible to apply in combination with MAO inhibitors.

Fluvoksamin — powerful inhibitor of P450 1A2 cytochrome, and to a lesser extent — P450 2C and P450 3A4. Drugs which are considerably metabolized by these isoenzymes are removed and can have higher concentration in a blood plasma in case of co-administration with fluvoksaminy more slowly. It is especially important for drugs which are characterized by the small width of therapeutic action. Patients need careful observation, if necessary correction of doses is recommended.

Fluvoksamin has the minimum inhibiting effect on P450 2D6 cytochrome and probably does not influence not oxidizing metabolism and renal excretion.

P450 1A2 cytochrome. At simultaneous use of Fevarina® increase in earlier stable levels of tricyclic antidepressants (кломипрамин, Imipraminum, amitriptyline) and neuroleptics (clozapine, olanzapine) which are substantially metabolized by P450 1A2 tsitokhroma was observed. In this regard the dose decline of these drugs can be recommended.

The patients who are at the same time accepting флувоксамин and the drugs which are characterized by the small width of therapeutic action, metabolized P450 1A2 cytochrome (such as такрин, theophylline, methadone, мексилетин) have to be under careful observation. If necessary it is necessary to modify dosages of these drugs.

At use in a combination with warfarin significant increase in concentration of warfarin in a blood plasma and lengthening of PV was observed.

It was reported about isolated cases of cardiotoxicity at simultaneous use of a fluvoksamin with thioridazine.

In the researches devoted to studying of interactions of Fevarina® increase in concentration of propranolol after introduction of Fevarina® was noted. In this regard it is possible to recommend a propranolol dose decline in case of additional purpose of Fevarina®.

During reception of a fluvoksamin caffeine level in plasma can increase. Therefore at consumption of large numbers of the drinks containing caffeine and at development of such adverse effects of caffeine as a tremor, heartbeat, nausea, concern, sleeplessness, it is necessary to reduce consumption of caffeine for reception of a fluvoksamin.

At a concomitant use of a fluvoksamin and a ropinirol concentration of the last in plasma can increase, thus increasing risk of development of its overdose. In such cases it is recommended to control a dosage of a ropinirol or to lower it for the period of treatment fluvoksaminy.

P450 2C cytochrome. The patients who are at the same time accepting флувоксамин and the drugs which are characterized by the small width of therapeutic action and exposed to metabolism by P450 2C cytochrome (Phenytoinum) have to be under careful observation, correction of dosages of these drugs is recommended.

P450 3A4 cytochrome. Terfenadin, астемизол, цизаприд — see. "Precautionary measures".

The patients who are at the same time accepting флувоксамин and the drugs which are characterized by the small width of therapeutic action and exposed to metabolism by P450 3A4 cytochrome (such as carbamazepine, cyclosporine), have to be under careful observation, correction of dosages of these drugs is recommended.

At co-administration with fluvoksaminy such benzodiazepines which are exposed to oxidizing metabolism as to triazoles, midazolam, to alprazola and diazepam, increase in their concentration in plasma is possible. The dosage of these benzodiazepines should be reduced by time of reception of a fluvoksamin.

Glyukuronization. Fluvoksamin does not exert impact on concentration of digoxin in plasma.

Renal excretion. Fluvoksamin does not exert impact on concentration of an atenolol in plasma.

Pharmakodinamichesky reactions. In case of the combined reception of a fluvoksamin with serotonergic drugs (триптанс, inhibitors of the return serotonin reuptake), tramadoly, serotonergic effects of a fluvoksamin can amplify (see. "Precautionary measures").

Fluvoksamin is applied with lithium drugs to treatment of the heavy patients who are badly answering pharmacotherapy. Lithium and, perhaps, tryptophane is strengthened by serotonergic effects of Fevarin ® and therefore treatment by such combination has to be carried out with care.

At a concomitant use of peroral anticoagulants and the fluvoksamina can increase risk of development of hemorrhages. Such patients have to be under observation of the doctor.

Contraindications:

- hypersensitivity to a fluvoksamin to a maleate or to one of the fillers which are a part of drug;
- concomitant use of a tizanidin and MAO inhibitors.

Treatment fluvoksaminy can be begun in 2 weeks after the termination of reception of the MAO irreversible inhibitor or next day after reception of the MAO reversible inhibitor. The period between the termination of reception of a fluvoksamin and the beginning of therapy by any MAO inhibitor has to make, at least, a week.

With care:
- liver and renal failure;
- spasms in the anamnesis, epilepsy;
- advanced age;
- patients with tendency to bleedings (thrombocytopenia);
- pregnancy.
It is not recommended to apply to treatment of a depression at children (there is no clinical experience).

Use at pregnancy and feeding by a breast
Data of a small number of observations did not reveal an adverse effect of a fluvoksamin on pregnancy. The potential risk is unknown. During pregnancy it is necessary to be careful. Separate cases of a withdrawal at newborns after use of a fluvoksamin were described during pregnancy.

Феварин® gets in small amounts into breast milk. In this regard it cannot be applied during breastfeeding.

Overdose:

Symptoms: the most characteristic — gastrointestinal frustration (nausea, vomiting and diarrhea), drowsiness and dizziness. Besides, there are messages on cardiovascular disturbances (tachycardia, bradycardia, arterial hypotension), abnormal liver functions, spasms and even a coma. So far over 300 messages on cases of deliberate overdose of Fevarina® arrived. The highest registered dose of Fevarina® received by one patient made 12 g; this patient was cured as a result of symptomatic therapy. More serious complications were observed in cases of deliberate overdose of Fevarina® against the background of the accompanying pharmacotherapy.

Treatment: a gastric lavage which has to be carried out as soon as possible after administration of drug, and also symptomatic therapy. Besides, multiple dose of absorbent carbon is recommended. The profound diuresis or dialysis are represented unjustified. The specific antidote does not exist.

Storage conditions:

In the dry, protected from a direct sunlight place, at a temperature not above 20 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

In piece blister 15 or 20; in a pack cardboard 1, 2, 3 or 4 blisters.