Description
Release form
coated tablets 50, 100 mg: 15 tablets or 20 tablets in PVC / blister. 1.2, 3 or 4 blisters in a cardboard box along with instructions for use.
Pharmacological action of
Pharmacodynamics of
The mechanism of action of Fevarin is associated with selective inhibition of serotonin reuptake by neurons in the brain and has a minimal effect on the noradrenergic system. Fevarin ® has a weak ability to bind to a-adrenergic, b-adrenergic, histaminergic, m-cholinergic receptors, dopaminergic or serotonergic receptors.
Pharmacokinetics
Absorption:
After oral administration, fluvoxamine is completely absorbed from the gastrointestinal tract. The maximum concentration of the drug in plasma is 3-8 hours after administration. Absolute bioavailability is 53% after primary metabolism in the liver. The simultaneous administration of fluvoxamine with food does not affect the pharmacokinetics.
Distribution:
The binding of fluvoxamine to plasma proteins is 80% (in vitro). Distribution volume – 25 l / kg.
Metabolism:
Fluvoxamine metabolism occurs mainly in the liver. Although the isoenzyme 2D6 of cytochrome P 450 is the main one in the metabolism of fluvoxamine, the concentration of the drug in the blood plasma in individuals with reduced function of this isoenzyme is not much higher than in individuals with a normal metabolism. The average half-life from plasma, amounting to a single dose of 13-15 hours, increases slightly with multiple doses (17-22 hours), and the equilibrium concentration in blood plasma is usually reached within 10-14 days. Fluvoxamine undergoes biotransformation in the liver (mainly by oxidative demethylation) to at least nine metabolites that are excreted through the kidneys. The two main metabolites have insignificant pharmacological activity. Other metabolites are probably pharmacologically inactive. Fluvoxamine significantly inhibits cytochrome P450 1A2, moderately inhibits cytochrome P450 2C and P450 ZA4, and slightly inhibits cytochrome P450 2D6. The pharmacokinetics of a single dose of fluvoxamine is linear. The equilibrium concentration of fluvoxamine is higher than the concentration of a single dose, and disproportionately higher at higher daily doses.
Special patient groups:
The pharmacokinetics of fluvoxamine are the same in healthy people, the elderly, and patients with kidney failure. Fluvoxamine metabolism is reduced in patients with liver disease. The equilibrium plasma concentration of fluvoxamine is twice as high in children (aged 6 11 years) than in adolescents (aged 12 17 years). The concentration of the drug in blood plasma in adolescents is similar to that in adults.
Indications
Treatment and prevention of depression, treatment of symptoms of obsessive-compulsive disorders.
Contraindications
Severe impaired liver function, simultaneous use of MAO inhibitors, children under 8 years old, hypersensitivity to fluvoxamine.
Pregnancy and lactation
A small number of observations do not indicate any adverse effects of fluvoxamine during pregnancy. To date, no other epidemiological data is available.
The potential risk to humans is unknown. The drug should be prescribed to pregnant women with caution.
Certain cases of withdrawal symptoms in newborns have been described after the use of fluvoxamine in late pregnancy.
In some newborns after exposure to selective serotonin reuptake inhibitors in the third trimester of pregnancy, feeding and / or breathing difficulties, convulsive disorders, unstable body temperature, hypoglycemia, tremors, muscle tone disorders, increased neuro-reflex irritability syndrome and continuous crying, which could require longer hospitalization. Fluvoxamine passes into breast milk. In this regard, the drug should not be used during lactation.
Special instructions
As with other psychotropic drugs, alcohol is not recommended during treatment with Fevarin ®.
Suicide / suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts or suicidal behavior (self-harm or suicide). This risk persists until significant improvement. Since improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until such improvement appears.
In clinical practice, an increased risk of suicide in the early stages of recovery is widespread.
Obsessive-compulsive disorders may also be associated with an increased risk of suicidal events. In addition, these conditions may be associated with severe depression. Therefore, in the treatment of patients with obsessive-compulsive disorder, the same precautions should be observed, as in the treatment of patients with severe depression.
Patients who have a history of suicide or have a history of suicidal ideation are known to have a greater risk of suicidal thoughts or suicidal behaviors before treatment and should be carefully observed during treatment.
Careful monitoring of patients, especially those at high risk, should accompany drug therapy, especially in its early stages and after dose changes. It is necessary to warn patients (and carers) about the need to monitor any clinical deterioration, suicidal behavior or suicidal thoughts, unusual changes in behavior, and immediately consult a specialist if such symptoms appear.
Children’s population
Fluvoxamine should not be used to treat children and adolescents under 18 years of age, with the exception of patients with obsessive-compulsive disorder. Due to a lack of clinical experience, the use of fluvoxamine in children for the treatment of depression cannot be recommended. In clinical trials conducted among children and adolescents, suicidal behavior (suicidal attempts and thoughts) and hostility (mainly aggression, oppositional behavior and anger) were observed more often in patients receiving antidepressant drugs compared with placebo. If, on the basis of clinical need, a decision on treatment is made, the patient should be carefully monitored for suicidal symptoms.
In addition, long-term safety data for children and adolescents, concerning the growth, development and formation of cognitive behavior are absent.
Adults (18 to 24 years old)
A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders revealed an increased risk of suicidal behavior when taking antidepressants compared with placebo in patients under 25 years of age. When prescribing fluvoxamine, the risk of suicide and the benefits of its use should be correlated.
Elderly patients
The data obtained from the treatment of elderly patients and younger patients indicate that there are no clinically significant differences between their daily doses. However, increasing doses of the drug in elderly patients should always be slower and with more caution.
Akatisia / psychomotor agitation
The development of akathisia associated with fluvoxamine is characterized by subjectively unpleasant and painful anxiety. The need to move was often accompanied by an inability to sit or stand still. The development of this condition is most likely during the first few weeks of treatment. Increasing the dose of the drug in patients with such symptoms may worsen their condition.
Treatment of patients suffering from hepatic or renal failure should be started with low doses and such patients should be under strict medical supervision. In rare cases, treatment with fluvoxamine can lead to increased activity of liver enzymes, most often accompanied by appropriate clinical symptoms, and in such cases, Fevarin ® should be discontinued.
Nervous System Disorders
Caution should be exercised when prescribing the drug to patients with a history of seizures. Fluvoxamine should be avoided in patients with unstable epilepsy, and patients with stable epilepsy should be closely monitored. Treatment with Fevarin ® should be discontinued if epileptic seizures occur or their frequency increases.
Rare cases of the development of a serotonergic syndrome or condition similar to a malignant antipsychotic syndrome that may be associated with fluvoxamine are described, especially in combination with other serotonergic and / or antipsychotic drugs. Since these syndromes can lead to potentially life-threatening conditions, manifested by hyperthermia, muscle stiffness, myoclonus, lability of the autonomic nervous system with possible rapid changes in vital parameters (pulse, respiration, blood pressure, etc.), changes in mental status, including confusion, irritability, extreme agitation, reaching delirium or coma – in such cases, treatment with fluvoxamine should be discontinued and appropriate symptomatic treatment should be initiated.
Metabolic and nutritional disorders.
As with other selective serotonin reuptake inhibitors, hyponatremia, which undergoes reverse development after the withdrawal of fluvoxamine, is possible in rare cases. Some cases have been caused by syndrome of insufficient secretion of antidiuretic hormone. These cases were mainly observed in elderly patients.
Blood glucose control (i.e. hyperglycemia, hypoglycemia, impaired glucose tolerance), especially in the early stages of treatment. In the case of the appointment of fluvoxamine to patients with a history of diabetes, a dose adjustment of antidiabetic drugs may be required.
The most frequently observed symptom associated with the use of Fevarin ® is nausea, sometimes accompanied by vomiting. This side effect usually disappears during the first two weeks of treatment.
Hematologic disorders
There are reports of intradermal hemorrhages, such as ecchymoses and purpura, as well as hemorrhagic manifestations (for example, gastrointestinal bleeding) observed with the use of selective serotonin reuptake inhibitors. Caution should be exercised when prescribing these drugs in elderly patients and patients simultaneously receiving drugs that act on platelet function (for example, atypical antipsychotics and phenothiazines, many tricyclic antidepressants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs), or drugs that increase the risk of bleeding as well as in patients with a history of bleeding or who are prone to bleeding (for example, with thrombocytopenia )
Disorders of cardiac activity
Increased risk of lengthening the QT / paroxysmal ventricular tachycardia interval of the pirouette type with the combination therapy of fluvoxamine with terfenadine or astemizole or cisapride, due to an increase in the concentration of the latter in blood plasma. Therefore, fluvoxamine should not be prescribed along with these drugs.
Fluvoxamine may cause a slight decrease in heart rate (2-6 beats per minute).
Withdrawal reactions
With discontinuation of fluvoxamine, withdrawal symptoms may develop, although available data from preclinical and clinical studies have not revealed a dependence on treatment with fluvoxamine. Symptoms noted in case of drug withdrawal: dizziness, paresthesia, headache, nausea, anxiety. Most of these symptoms are mild and stop on their own. Upon termination of treatment with the drug, a gradual dose reduction is recommended.
Ability to drive a car and use machines and mechanisms.
Fevarin prescribed to healthy volunteers in doses up to 150 mg, did not affect or had a slight effect on the ability to drive a car and drive cars. At the same time, there are reports of drowsiness observed during treatment with fluvoxamine. In this regard, caution is advised until the final determination of an individual response to the drug.
Ingredients
Active ingredient: fluvoxamine maleate – 50, 100 mg
excipients: mannitol – 15 mg (303.0 mg), corn starch – 40.0 mg (80.0 mg), pregel starch lowered – 6.0 mg (12.0 mg), sodium stearyl fumarate – 1.8 mg (3.5 mg), colloidal silicon dioxide – 0.8 mg (1.5 mg)
shell: hypromellose – 4.1 mg ( 5.6 mg), macrogol 6000 – 1.5 mg (2.0 mg), talc – 0.3 mg (0.4 mg), titanium dioxide (E171) – 1.5 mg (2.1 mg).
Dosage and Administration
Fluvoxamine tablets should be taken orally without chewing with water.
Depression
Adults
The recommended starting dose for adults is 50 or 100 mg (once, in the evening). A gradual increase in dose to an effective level is recommended.
An effective daily dose, usually 100 mg, is selected individually depending on the patient’s response to treatment. The daily dose can reach 300 mg. Daily doses in excess of 150 mg should be divided into several doses.
According to official WHO guidelines, antidepressant treatment should be continued for at least 6 months in remission after a depressive episode.
To prevent relapse of depression, it is recommended to take 100 mg of Fevarin® once a day, daily.
Children
Due to the lack of clinical experience, Fevarin is not recommended for the treatment of depression in children under 18 years of age.
Obsessive-Compulsive Disorder (OCD)
Adults
The recommended starting dose for adults is 50 mg Fevarin® per day for 34 days. An effective daily dose is usually from 100 to 300 mg. Doses should be increased gradually until an effective daily dose is reached, which should not exceed 300 mg in adults. Doses up to 150 mg can be taken once a day, preferably in the evening. Daily doses in excess of 150 mg are recommended to be distributed in 2 or 3 doses.
Children over 8 years of age and adolescents
The initial dose is 25 mg / day at a time. Maintenance dose 50 – 200 mg / day. In the treatment of OCD in children aged 8 to 18 years, the daily dose should not exceed 200 mg. Daily doses in excess of 100 mg are recommended to be divided into 2 or 3 doses.
With a good therapeutic response to the drug, treatment can be continued with an individually selected daily dose. If improvement is not achieved after 10 weeks, fluvoxamine treatment should be reviewed. So far, no systematic studies have been organized that could answer the question of how long fluvoxamine can be treated, however, obsessive-compulsive disorders are chronic, and therefore, prolongation of fluvoxamine treatment beyond 10 weeks can be considered appropriate in patients who responded well on this drug. The selection of the minimum effective maintenance dose should be carried out with caution on an individual basis. Periodically, it is necessary to re-evaluate the need for treatment. Some clinicians recommend concomitant psychotherapy in patients responding well to pharmacotherapy.
Treatment of patients with hepatic or renal failure should begin with low doses under strict medical supervision.
Side effects of
Some of the side effects observed during clinical trials were often associated with symptoms of depression and not with treatment with Fevarin ®.
Frequent
Common disorders: asthenia, malaise.
Disorders of the heart: palpitations, tachycardia.
Disorders of the gastrointestinal tract: abdominal pain, constipation, diarrhea, dry mouth, dyspepsia, nausea, vomiting.
Disorders of the nervous system: irritability, anxiety, agitation, dizziness, insomnia or drowsiness, tremors, headache.
Disorders of the skin and subcutaneous tissue: increased sweating.
Metabolism and nutritional disorders: anorexia.
Infrequent
Vascular disorders: orthostatic hypotension
Musculoskeletal and connective tissue disorders: arthralgia, myalgia.
Disorders from the nervous system: ataxia, extrapyramidal disorders.
Mental disorders: state of confusion, hallucinations.
Violations of the genitals and mammary gland: violation (delay) of ejaculation.
Disorders of the skin and subcutaneous tissues: skin hypersensitivity reactions, (including rash, itching, angioedema).
Rare
Disorders of the liver: impaired liver function (increased activity of liver enzymes).
Disorders of the nervous system: convulsions.
Mental disorders: mania
Genital and breast disorders: galactorrhea.
Disorders of the skin and subcutaneous tissue: photosensitivity reactions.
In addition to the side effects described during clinical trials, the following side effects have been reported during post-marketing use of fluvoxamine. The exact frequency cannot be provided and is therefore classified as unknown .
Disorders of the blood and lymphatic system: hemorrhages (e.g., gastrointestinal bleeding, ecchymosis, purpura).
Disorders of the endocrine system: insufficient secretion of antidiuretic hormone.
Metabolic and nutritional disorders: hyponatremia, weight gain, weight loss.
Disorders of the nervous system: serotonin syndrome phenomena similar to the malignant antipsychotic syndrome akathisia / psychomotor agitation paresthesia dysgeusia.
Mental disorders: cases of suicidal thoughts and suicidal behavior were reported during treatment with fluvoxamine or shortly after it.
Disorders of the kidneys and urinary tract: disorders of urination (including urinary retention, urinary incontinence, rapid urination, nocturia and enuresis).
Disorders of the genitals and mammary gland: anorgasmia.
General Disorders: drug withdrawal syndrome, including neonatal withdrawal syndrome.
Overdose of
Symptoms of
The most common symptoms include gastrointestinal upsets (nausea, vomiting, and diarrhea), drowsiness, and dizziness. In addition, there are reports of violations. cardiac activity (tachycardia, bradycardia, arterial hypotension), impaired liver function, convulsions and coma.
Fluvoxamine has a greater breadth of therapeutic dose in terms of overdose safety. Since the launch of the market, reports of deaths attributed to an overdose of fluvoxamine alone have been extremely rare. The highest recorded dose of fluvoxamine taken by one patient was 12 g. This patient was completely cured. More serious complications were observed in cases of intentional overdose of fluvoxamine in combination with other drugs.
Treatment
There is no specific antidote for fluvoxamine: In case of overdose, gastric lavage is recommended, which should be carried out as soon as possible after taking the drug, as well as symptomatic treatment. In addition, repeated intake of activated carbon is recommended, if necessary, the appointment of osmotic laxatives. Forced diuresis or dialysis is not effective.
Storage conditions
List B.
In the original package, in a dry, dark place at a temperature not exceeding 25 ° C.
Keep out of the reach and sight of children!
The Expiration of
is 3 years.
active substance
fluvoxamine
conditions granted through pharmacies
In retseptu
lekarstvennaja form
tablets