Expiration date: 04/2025

Structure and Composition: 

Film-coated tablets. 1 tablet contains fluvoxamine maleate 50 or 100 mg

Excipients: Mannitol - 152 or 303 mg maize starch - 40 or 80 mg pregelatinized starch - 6 or 12 mg Sodium stearyl fumarate - 1.8 or 3.5 mg anhydrous colloidal silica - 0.8 or 1.5 mg

sheath: hypromellose - or 4.1 mg Macrogol 6000 5.6 - 1.5 mg talc or 2 - 0.3, or 0.4 mg titanium dioxide (E171) - 1.5 or 2.1 mg

The product does not contain any lactose or sugar (E121).

in a blister pack of 15 pieces.

Description pharmaceutical form:

Tablets 50 mg: Round, biconvex tablets, coated white on one side of the tablet - the risk and marking "291" on both sides of the risks, on the other - "the S" over the icon 7.

Tablets 100 mg: oval, biconvex film-coated tablets in white on one side of the tablet - the risk and marking "313" on both sides of the risks, on the other - "the S" over the icon 7.

Pharmacokinetics:

If ingestion is completely absorbed from the gastrointestinal tract. Cmax achieved after 3-8 hours, the equilibrium concentration - 10-14 days. The absolute bioavailability is 53% following primary metabolism in the liver. Simultaneous reception Fevarin with food does not affect the pharmacokinetics.

Binding to plasma proteins - about 80%. The volume of distribution - 25 l / kg.

Fevarin metabolism occurs mainly in the liver. Although cytochrome P450 2D6 isoenzyme is the main fluvoxamine in metabolism, the drug concentration in blood plasma in patients with impaired function of this isoenzyme is not much higher than those with normal metabolism. The average T1 / 2 of the blood plasma constituting a single dose for 13-15 h, increases slightly with multiple admission (17-22 h), and the equilibrium concentration in plasma is usually achieved within 10-14 days.

Fevarin biotransformation in the liver (mainly by oxidative demethylation) at least 9 to metabolites that are excreted through the kidneys. 2 major metabolite have negligible pharmacological activity. Other metabolites may pharmacologically inactive. Fluvoxamine significantly inhibit cytochrome P450 1A2, moderately inhibits cytochrome P450 2C and P450 3A4, slightly - cytochrome P450 2D6.

The pharmacokinetics of fluvoxamine is the same in healthy people, the elderly and patients with renal insufficiency. Metabolism is reduced in patients with liver disease.

Steady-state plasma concentrations of fluvoxamine in children aged 6-11 years - twice as high as in adolescents (12-17 years). Drug concentrations in the blood plasma of adolescents are similar to those in adults.

Description of the pharmacological actions:

Selectively inhibits the reuptake of serotonin neurons in the brain and is characterized by a minimal effect on the noradrenergic transmission. Fevarin unexpressed has the ability to bind to alpha- and beta-adrenergic, histaminergic, m-cholinergic, dopaminergic or serotonergic receptors.

Testimony:

• Depression different genesis
  
• obsessive-compulsive disorders.
  

Contraindications:

• hypersensitivity to fluvoxamine maleate or one of the excipients included in the formulation
  
• concomitant use of tizanidine and MAO inhibitors.
  

Treatment with fluvoxamine can be initiated within 2 weeks after discontinuation of an irreversible MAO inhibitor, or the day after receiving a reversible MAO inhibitor. The time interval between the cessation and start receiving fluvoxamine therapy by any MAO inhibitor must be a minimum of a week.

Carefully:

• liver and kidney failure
  
• cramps in the history of epilepsy
  
• elderly age
  
• patients with a tendency to bleeding (thrombocytopenia)
  
• pregnancy.
  

Not recommended for use in the treatment of depression in children (no clinical experience).

Application of pregnancy and breastfeeding:

These few observations did not reveal any adverse effects of fluvoxamine on pregnancy. The potential risk is unknown. During pregnancy should be careful. some cases of neonatal withdrawal of fluvoxamine after use during pregnancy were described.

Fevarin penetrates in small quantities in breast milk. Therefore it can not be applied during breastfeeding.

Side effect:

The most frequently observed symptom associated with the use of Fevarin is nausea, sometimes accompanied by vomiting. This side effect is usually disappears within the first 2 weeks of treatment.

Some side effects observed in clinical trials, have often been associated with depressive symptoms, rather than the treatment conducted Fevarin.

General: common (1-10%) - asthenia, headache, and malaise.

Since the cardiovascular system: often (1-10%) - palpitations, tachycardia occasionally (less than 1%) - postural hypotension.

On the part of the digestive tract: common (1-10%) - abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia rare (less than 0.1%) - abnormal liver function (elevated liver transaminases).

CNS: often (1-10%) - nervousness, anxiety, agitation, dizziness, insomnia or drowsiness, tremors occasionally (less than 1%) - Ataxia, confusion, extrapyramidal disorders, hallucinations rarely (less than 0.1%) - seizures, mania.

Skin: common (1-10%) - sweating occasionally (less than 1%) - skin hypersensitivity reactions (rash, pruritus, angioedema) rarely (less than 0.1%) - photosensitivity.

From the musculoskeletal system: sometimes (less than 1%) - arthralgia, myalgia.

From the reproductive system: occasionally (less than 1%) - delayed ejaculation rarely (less than 0.1%) - galactorrhea.

Other: rarely (less than 0.1%) - a body mass changes in serotonergic syndrome, a condition similar to neuroleptic malignant syndrome, hyponatremia and syndrome of inadequate secretion of antidiuretic hormone is very rare - paresthesia, taste perversion, and anorgasmia.

Upon termination of fluvoxamine may develop withdrawal symptoms - dizziness, paresthesia, headache, nausea, anxiety (most of the symptoms are mild and self-cropped). When the drug is recommended cancellation of a gradual reduction in dose.

Hemorrhagic manifestations - ecchymosis, purpura, gastrointestinal bleeding.

Drug Interactions:

Fevarin should not be used in combination with MAO inhibitors.

Fluvoxamine - a potent inhibitor of cytochrome P450 1A2, and to a lesser extent - P450 2C and P450 3A4. Drugs which are largely metabolized by these isoenzymes, displayed slower and may have higher plasma concentrations when co-administration with fluvoxamine. This is particularly important for drugs which are characterized by small breadth of therapeutic action. Patients need careful monitoring, dose adjustment is recommended when necessary.

Fluvoxamine has a minimal inhibitory effect on cytochrome P450 2D6, and probably does not affect the non-oxidative metabolism and renal excretion.

Cytochrome P450 1A2. With simultaneous use of Fevarin observed increase in previously stable levels of tricyclic antidepressants (clomipramine, imipramine, amitriptyline) and neuroleptics (clozapine, olanzapine) which are largely metabolized by cytochrome P450 1A2. In connection with this reduction can be recommended dose of these drugs.

Patients simultaneously taking fluvoxamine and preparations characterized by low breadth of therapeutic action metabolized by cytochrome P450 1A2 (such as tacrine, theophylline, methadone, mexiletine) should be carefully monitored. If necessary, adjust the dosage of these drugs.

When used in combination with warfarin showed a significant increase in the concentrations of warfarin in plasma and PT prolongation.

It was reported a few cases of cardiotoxicity, while the use of fluvoxamine with thioridazine.

In studies that examine interactions Fevarin, was an increase in propranolol concentrations after administration of Fevarin. In connection with this reduction can be recommended in the case of propranolol dose Fevarin supplemental assignment.

While receiving fluvoxamine caffeine plasma levels may be increased. Therefore, the consumption of large amounts of beverages containing caffeine and the development of such adverse effects of caffeine as tremor, palpitations, nausea, restlessness, insomnia, you need to reduce your intake of caffeine for a period of fluvoxamine.

At the same time taking ropinirole and fluvoxamine may increase the concentration of the latter in the plasma, thereby increasing the risk of overdose. In such cases it is recommended to control the dosage of ropinirole or lower it during treatment with fluvoxamine.

Cytochrome P450 2C. Patients simultaneously taking fluvoxamine and preparations characterized by low breadth of therapeutic action and is metabolized by cytochrome P450 2C (phenytoin) should be under close supervision, adjustment is recommended dosages of these drugs.

Cytochrome P450 3A4. Terfenadine, astemizole, cisapride - see "Precautions"..

Patients simultaneously taking fluvoxamine and preparations characterized by low breadth of therapeutic action and is metabolized by cytochrome P450 3A4 (such as carbamazepine, ciclosporin) should be under close supervision, adjustment is recommended dosages of these drugs.

When concomitant administration with fluvoxamine such benzodiazepines undergoing oxidative metabolism as triazolam, midazolam, alprazolam and diazepam, may increase their concentration in plasma. The dosage of these benzodiazepines should be reduced at the time of fluvoxamine.

Glucuronidation. Fluvoxamine has no effect on plasma concentration of digoxin.

Renal excretion. Fluvoxamine has no effect on the plasma concentration of atenolol.

Pharmacodynamic reaction. When combined with fluvoxamine serotonergic drugs (triptans, serotonin reuptake inhibitors), tramadol may increase serotonergic effects of fluvoxamine (see. "Precautions").

Fluvoxamine is used with lithium therapy for the treatment of patients with severe, poorly responsive to pharmacotherapy. Lithium and possibly tryptophan enhance serotonergic effects of Fevarin and therefore this combination treatment should be carried out with caution.

At the same time taking oral anticoagulants and fluvoxamine may increase the risk of hemorrhage. These patients should be under a doctor's supervision.

Dosage and administration:

Inside, with liquid squeezed small amounts of water.

Depression. The recommended starting dose is 50 or 100 mg (once in the evening). It recommended starting dose of a gradual increase to a level effective. The effective daily dose is usually 100 mg, chosen individually, depending on the patient's response to treatment. The daily dose may reach 300 mg. Daily doses greater than 150 mg should be distributed on several stages. In accordance with the official recommendations of the WHO, antidepressant medication should be continued for at least 6 months after remission of a depressive episode. For the prevention of relapse of depression it is recommended to take 100 mg Fevarin 1 per day.

Obsessive-compulsive disorder. It is recommended to start with a dose of 50 mg Fevarin a day for 3-4 days. The effective daily dose is usually from 100 to 300 mg. Dosages should be increased gradually until the effective daily dose should not exceed 300 mg in adults. Doses up to 150 mg may be administered as a single, preferably in the evening. Daily doses greater than 150 mg is recommended to distribute on 2 or 3 doses.

Doses for children over 8 years and adolescents: initial - 25 mg / day on 1 reception, maintenance - 50-200 mg / day. The daily dose should not exceed 200 mg. Daily doses of 100 mg is recommended to distribute on 2 or 3 doses.

With good response to drug treatment can be continued at a daily dose of individually selected. If no improvement is achieved after 10 weeks of treatment, fluvoxamine should be discontinued. So far, no systemic studies were organized, which could answer the question of how long can be carried out treatment with fluvoxamine, but obsessive-compulsive disorders are chronic, and therefore can be considered appropriate extension of Luvox treatment over 10 weeks in patients with a good response for this drug. Selection of the minimum effective maintenance dose should be administered with caution individually. Some clinicians recommend carrying out concomitant therapy in patients who respond well to drug therapy.

Treatment of patients suffering from hepatic or renal insufficiency should start with the smallest doses under strict medical supervision.

Due to lack of clinical experience Fevarin is not recommended for the treatment of depression in children.

Overdose:

Symptoms: The most typical - gastrointestinal disorders (nausea, vomiting and diarrhea), somnolence and dizziness. In addition, there are reports of cardiovascular disorders (tachycardia, bradycardia, hypotension), liver function disturbances, convulsions and even coma. To date, it received more than 300 reported cases of intentional overdose of Fevarin. The highest registered dose of Fevarin, received one patients was 12 g, this patient was cured as a result of symptomatic therapy. More serious complications were observed in cases of deliberate overdose of Fevarin with concurrent pharmacotherapy.

Treatment: gastric lavage, which should take place as soon as possible after taking the drug, as well as symptomatic therapy. In addition, multiple dose activated charcoal is recommended. Diuresis or dialysis appear to be unjustified. There is no specific antidote.

Precautionary measures:

During treatment with alcohol is not recommended.

In patients suffering from depression, there is usually a high probability of a suicide attempt, which may be stored until a sufficient remission. Such patients should be monitored.

Treatment of patients suffering from hepatic or renal insufficiency should start with the lowest effective dose of Fevarin under strict medical supervision. In rare cases, Fevarin treatment can lead to increased levels of hepatic transaminases, often accompanied by a corresponding clinical symptoms. In these cases, Fevarin should be abolished.

It may be broken monitor the level of glucose in the blood, especially in the early stages of treatment. It may require a dosage adjustment of antidiabetic drugs.

Caution should be exercised when administering the drug to patients with seizures in history. Fevarin should be avoided in patients with unstable epilepsy, and with stable epilepsy patients should be under strict medical supervision. Fevarin treatment should be discontinued in the event of seizures or increase their frequency.

Described rare cases of serotonin syndrome or condition, such neuroleptic malignant syndrome, which can be associated with taking fluvoxamine in combination with other serotonergic antidepressants and neuroleptics. As these syndromes may result in potentially life-threatening condition, manifested by hyperthermia, muscle rigidity, myoclonus, lability of the autonomic nervous system with possible rapid changes in vital parameters, changes in mental status, including increased irritability, agitation, confusion, delirious disorders and coma, - treatment with fluvoxamine should be discontinued. If necessary to begin appropriate treatment.

As with other selective serotonin reuptake inhibitors, in rare cases in patients receiving fluvoxamine may cause hyponatremia, which regress after discontinuation of the drug. Some cases have been caused by the syndrome of inadequate secretion of antidiuretic hormone. In general, these cases were observed in elderly patients.

There are reports of such intradermal hemorrhages as ecchymosis and purpura, as well as haemorrhagic manifestations (eg gastrointestinal bleeding), observed in the application of the electoral serotonin reuptake inhibitors. Caution must be exercised in the appointment of these drugs in elderly patients and in patients concomitantly receiving drugs acting on platelet function (atypical antipsychotics and phenothiazines, most tricyclic antidepressants, aspirin, NSAIDs) or drugs that increase the risk of bleeding, as well as in patients with bleeding history and prone to bleeding (eg in patients with thrombocytopenia).

In combination therapy with fluvoxamine concentration of terfenadine, astemizole, or cisapride plasma may increase, increasing the risk of QT interval prolongation. Therefore, fluvoxamine should not be administered with these drugs.

The data obtained in the treatment of elderly patients and younger patients showed no clinically relevant differences between them are usually used in daily doses. However, increasing doses of the drug in elderly patients should always be done slowly and with a larger caution. Fevarin may lead to a slight decrease in heart rate (2-6 beats per minute).

Due to lack of clinical experience Fevarin is not recommended for the treatment of depression in children.

Fevarin, are appointed to healthy volunteers in doses up to 150 mg did not influence or have a negligible effect on the ability to drive a car or machine control. At the same time there are reports of sleepiness was noted during the drug treatment. Therefore caution is recommended to determine the final individual response to the drug.