Fevarin pills 100mg, 30pcs

Composition

Active ingredient: fluvoxamine maleate-100 mgsupport substances:  mannitol-303.0 mg, corn starch-80.0 mg, pregelatinized starch-12.0 mg, sodium stearyl fumarate-3.5 mg, colloidal silicon dioxide-1.5 mg shell:  hypromellose-5.6 mg, macrogol 6000-2.0 mg, talc-0.3 mg, titanium dioxide (E 171) – 2.1 mg

Pharmacological action

Pharmacotherapy group: antidepressant.

ATX code [M)6 AB 08].

Pharmacological action

Pharmacodynamics

The mechanism of action of Fevarin is associated with selective inhibition of serotonin reuptake by brain neurons and is characterized by a minimal effect on the noradrenergic system. Fevarin® has a weak ability to bind to a-adrenergic, b-adrenergic, histaminergic, m – cholinergic, dopaminergic or serotonergic receptors.

Pharmacokinetics

Suction:

After oral use, fluvoxamine is completely absorbed from the gastrointestinal tract. Maximum concentrations of the drug in the blood plasma are observed 3-8 hours after use. Absolute bioavailability is 53% after primary liver metabolism. Concomitant use of fluvoxamine with food does not affect the pharmacokinetics.

Distribution:

The binding of fluvoxamine to plasma proteins is 80% (in vitro). The volume of distribution is 25 l / kg.

Metabolism:

Fluvoxamine is primarily metabolized in the liver. Although cytochrome P450 2D6 isoenzyme is the main one in fluvoxamine metabolism, the concentration of the drug in blood plasma in individuals with reduced function of this isoenzyme is not much higher than in individuals with normal metabolism. The average plasma half-life, which is 13-15 hours for a single dose, slightly increases with repeated use (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 P 450 1 A 2, moderately inhibits cytochromes P 450 2 C and P 450 ZA 4, and slightly-cytochrome P 450 2D6. The pharmacokinetics of a single dose of fluvoxamine are linear. The steady-state concentration of fluvoxamine is higher than that of a single dose and disproportionately higher at higher daily doses.

Special patient groups:

The pharmacokinetics of fluvoxamine are similar in healthy people, the elderly, and patients with renal insufficiency. Fluvoxamine metabolism is reduced in patients with liver disease. Steady-state plasma concentrations of fluvoxamine are twice as high in children (aged 6-11 years) as in adolescents (aged 12-17 years). Concentrations of the drug in the blood plasma in adolescents are similar to those in adults.

Indications

Treatment and prevention of depression, treatment of symptoms of obsessive-compulsive disorders

Use during pregnancy and lactation

Data from a small number of observations do not indicate any adverse effects of fluvoxamine during pregnancy. To date, no other epidemiological data are available.

The potential risk to humans is unknown. The drug should be administered to pregnant women with caution.

There have been isolated cases of withdrawal symptoms in newborns following fluvoxamine use at the end of pregnancy.

Some newborns after exposure to selective serotonin reuptake inhibitors in the third trimester of pregnancy experienced difficulty feeding and / or breathing, convulsive disorders, unstable body temperature, hypoglycemia, tremor, muscle tone disorders, increased neuro-reflex excitability syndrome and continuous crying, which may require longer hospitalization. Fluvoxamine passes into breast milk. In this regard, the drug should not be used during lactation.

Contraindications

Severe hepatic impairment, concomitant use of MAO inhibitors, children under 8 years of age, hypersensitivity to fluvoxamine.

Side effects

Some of the side effects observed in clinical trials were often associated with symptoms of depression, rather than with treatment with Fevarin®.

Frequent (>1%) and general disorders: asthenia, malaise. Cardiac disorders: palpitations, tachycardia. Gastrointestinal disorders: abdominal pain, constipation, diarrhea, dry mouth, dyspepsia, nausea, vomiting. Nervous system disorders: increased excitability, anxiety, agitation, dizziness, insomnia or drowsiness, tremor, headache. Skin and subcutaneous tissue disorders: increased sweating. Metabolic and nutritional disorders: anorexia.

Infrequent (>0.1%) vascular disorders: orthostatic hypotonia musculoskeletal and connective tissue disorders: arthralgia, myalgia. Nervous system disorders: ataxia, extrapyramidal disorders. Mental disorders: a state of confused consciousness, hallucinations. Disorders of the genitals and breast: violation (delay) of ejaculation. Skin and subcutaneous tissue disorders: hypersensitivity skin reactions (including rash, pruritus, angioedema).

Rare (>0.01%) liver disorders: impaired liver function (increased activity of liver enzymes). Nervous system disorders: convulsions. Mental disorders: Manic disorders of the genitals and breast: galactorrhea. Skin and subcutaneous tissue disorders: photosensitivity reactions.

In addition to the side effects reported during clinical trials, the following side effects were 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 (for example, gastrointestinal bleeding, ecchymosis, purpura).

Endocrine system disorders:  insufficient secretion of antidiuretic hormone.

Metabolic and nutritional disorders:  hyponatremia, weight gain, weight loss.

Nervous system disorders:  serotonin syndrome; phenomena similar to neuroleptic malignant syndrome; akathisia/psychomotor agitation; paresthesias; dysgeusia.

Psychiatric disorders: Suicidal thoughts and suicidal behavior have been reported during or shortly after fluvoxamine treatment.

Kidney and urinary tract disorders:  urinary disorders (including urinary retention, urinary incontinence, frequent urination, nocturia, and enuresis).

Genital and breast disorders:  anorgasmia.

Common disorders:  drug withdrawal syndrome, including neonatal withdrawal syndrome.

Interaction

Fluvoxamine should not be used in combination with MAO inhibitors (see section “Contraindications”). Fluvoxamine significantly inhibits the cytochrome P4501A2 isoenzyme and, to a lesser extent, the P4502CAND P450A4 isoenzymes. Drugs that are largely metabolized by these isoenzymes are more slowly excreted and may have higher plasma concentrations if co-administered with fluvoxamine. This is especially important for drugs that have a narrow range of therapeutic effects. Patients need to be carefully monitored, and if necessary, it is recommended to adjust the dose of these drugs.

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

Cytochrome P 450 1 A2 Co-use of fluvoxamine has been associated with increased concentrations of tricyclic antidepressants (clomipramine, imipramine, amitriptyline) and neuroleptics (clozapine, olanzapine), which are largely metabolized by the cytochrome P 450 1 A2 isoenzyme. Therefore, if treatment with fluvoxamine is initiated, a reduction in the dose of these drugs should be considered.

Patients taking fluvoxamine concomitantly with drugs with a narrow therapeutic range that are metabolized by the cytochrome P4501a2 isoenzyme (such as tacrine, theophylline, methadone, mexiletine) should be closely monitored. If necessary, it is recommended to adjust the dose of these drugs. Isolated cases of cardiotoxicity have been reported with concomitant use of fluvoxamine and thioridazine. When fluvoxamine interacted with propranolol, an increase in plasma concentrations of propranolol was noted. In this regard, it is recommended to reduce the dose of propranolol in the case of simultaneous use with fluvoxamine. While taking fluvoxamine, the concentration of caffeine in the plasma may increase. Therefore, patients who consume large amounts of caffeinated beverages should reduce their intake while taking fluvoxamine, and when adverse effects of caffeine are observed, such as tremors, palpitations, nausea, anxiety, insomnia.

Concomitant use of fluvoxamine and ropinirole may increase the plasma concentration of ropinirole, thus increasing the risk of overdose. In such cases, it is recommended to monitor, or, if necessary, reduce the dose or cancel ropinirole during treatment with fluvoxamine.

Cytochrome P 450 2 S isoenzyme

Patients taking fluvoxamine concomitantly with drugs with a narrow therapeutic range that are metabolized by the cytochrome p450 – 2C isoenzyme (such as phenytoin) should be closely monitored, and dose adjustment of these drugs is recommended if necessary.

When fluvoxamine was used in combination with warfarin, there was a significant increase in plasma concentrations of warfarin and an elongation of prothrombin time.

Cytochrome P 450 isoenzyme FOR 4

Terfenadine, astemizole, cisapride: when combined with fluvoxamine, plasma concentrations of terfenadine, astemizole, or cisapride may increase, increasing the risk of QT prolongation/paroxysmal ventricular tachycardia of the “pirouette”type. Therefore, fluvoxamine should not be administered together with these drugs.

Patients taking fluvoxamine concomitantly with drugs with a narrow therapeutic range that are metabolized by the cytochrome P450-4 isoenzyme (such as carbamazepine, cyclosporine) should be closely monitored, and dose adjustment of these drugs is recommended.

Co-use with fluvoxamine of benzodiazepines undergoing oxidative metabolism, such as triazolam, midazolam, alprazolam and diazepam, may increase their plasma concentrations. The dose of these benzodiazepines should be reduced while taking fluvoxamine.

Glucuronidation

of Fluvoxamine does not affect the concentration of digoxin in plasma.

Renal excretion

Fluvoxamine does not affect the concentration of atenolol in plasma.

Pharmacodynamic interactions

In the case of combined use of fluvoxamine with serotonergic drugs (such as triptans, tramadol, selective serotonin reuptake inhibitors and St. John’s wort preparations), the serotonergic effects of fluvoxamine may increase (see “Special Instructions”). Fluvoxamine was used in combination with lithium preparations for the treatment of severe patients who did not respond well to pharmacotherapy. It should be noted that lithium (and possibly also tryptophan) enhances the serotonergic effects of the drug, and therefore this type of combined pharmacotherapy should be carried out with caution.

Concomitant use of oral anticoagulants and fluvoxamine may increase the risk of hemorrhage.

Such patients should be under the supervision of a doctor.

How to take, course of use and dosage

Fluvoxamine tablets should be taken orally, without chewing, with water.

Depressions

Adults

The recommended starting dose for adults is 50 or 100 mg (once, in the evening). It is recommended to gradually increase the dose to the effective level.

The 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 of more than 150 mg should be divided into several doses.

According to official WHO guidelines, antidepressant treatment should be continued for at least 6 months of remission after a depressive episode.

To prevent relapses 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 of Fevarin® per day for 3-4 days. The effective daily dose is usually between 100 and 300 mg. Doses should be increased gradually until the 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 of more than 150 mg are recommended to be divided into 2 or 3 doses.

Children over 8 years of age and teenagers

The initial dose is 25 mg / day in one dose. The maintenance dose is 50-200 mg / day. When treating OCD in children aged 8 to 18 years, the daily dose should not exceed 200 mg. Daily doses of more than 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 no improvement is achieved after 10 weeks, treatment with fluvoxamine should be reviewed. So far, no systematic studies have been conducted that could answer the question of how long fluvoxamine treatment can last, but obsessive-compulsive disorders are chronic in nature, and therefore it can be considered advisable to extend fluvoxamine treatment beyond 10 weeks in patients who responded well to 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 who have responded well to pharmacotherapy.

Treatment of patients with hepatic or renal insufficiency should begin with low doses under strict medical supervision.

Overdose

Symptoms

The most common symptoms include gastrointestinal disorders (nausea, vomiting, and diarrhea), drowsiness, and dizziness. In addition, there are reports of violations. cardiac activity (tachycardia, bradycardia, hypotension), liver function disorders, convulsions and coma.

Fluvoxamine has a wide therapeutic dose range in terms of overdose safety. Since its release to the market, deaths attributed to fluvoxamine overdose alone have been reported very rarely. The highest recorded dose of fluvoxamine taken by a single patient was 12 g. This patient was completely cured. More serious complications were observed in cases of deliberate 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 early as possible after taking the drug, as well as symptomatic treatment. In addition, it is recommended to repeatedly take activated carbon, if necessary, the appointment of osmotic laxatives. Forced diuresis or dialysis is not effective.

Special instructions

As with other psychotropic medications, alcohol consumption is not recommended during treatment with Fevarin®.

Suicide / suicidal thoughts or clinical worsening Depression is associated with an increased risk of suicidal thoughts or actions (self-harm or suicide). This risk persists until the condition improves significantly. Since improvement may not occur within the first few weeks of treatment or longer, patients should be closely monitored until such improvement occurs.

In clinical practice, there is a widespread increase in the risk of suicide in the early stages of recovery.

Obsessive-compulsive disorders may also be associated with an increased risk of suicidal events. In addition, these conditions can accompany deep depression. Therefore, when treating patients with obsessive-compulsive disorders, the same precautions should be observed as when treating patients with deep depression.

Patients with a history of suicide-related events or a significant degree of suicidal ideation are known to be at greater risk of suicidal thoughts or behaviors before starting treatment and should be carefully monitored during treatment.

Careful monitoring of patients, especially those at high risk, should accompany drug therapy, especially in its early stages and after dose changes. Patients (and their caregivers) should be warned to monitor any clinical deterioration, suicidal behavior or suicidal thoughts, or unusual behavioral changes, and immediately seek professional advice if such symptoms occur.

Children’s populationfluvoxamine should not be used for the treatment of children and adolescents under 18 years of age, except in 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 studies conducted among children and adolescents, suicidal behavior (suicidal attempts and thoughts) and hostility (mainly aggression, oppositional behavior, and anger) were observed more frequently in patients receiving an antidepressant compared to those receiving placebo. If a treatment decision is made based on a clinical need, the patient should be closely monitored for suicidal symptoms.

In addition, long-term safety data for children and adolescents regarding growth, development, and development of cognitive behavior are not available.

Adults (18-24 years old)A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders revealed an increased risk of suicidal behavior when taking antidepressants compared to placebo in patients younger than 25 years. When prescribing fluvoxamine, the risk of suicide and the benefits of its use should be correlated.

Elderly Patientsdata obtained in the treatment of elderly patients and younger patients indicate that there are no clinically significant differences between their usual daily doses. However, increasing the dose of the drug in elderly patients should always be carried out more slowly and with more caution.

Akathisia / psychomotor AGITATIONTHE development of akathisia associated with fluvoxamine use is characterized by subjectively unpleasant and excruciating anxiety. The need to move was often accompanied by an inability to sit or stand still. This condition is most likely to develop 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 insufficiency should begin with low doses and such patients should be under strict medical supervision. In rare cases, treatment with fluvoxamine may 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 strictly monitored. Treatment with Fevarin should be discontinued if epileptic seizures occur or their frequency increases.

Rare cases of serotonergic syndrome or a condition similar to neuroleptic malignant syndrome that may be associated with the use of fluvoxamine, especially in combination with other serotonergic and/or neuroleptic drugs, have been described. Since these syndromes can lead to potentially life-threatening conditions, such as hyperthermia, muscle rigidity, 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, fluvoxamine treatment should be discontinued and appropriate symptomatic treatment should be initiated.

Metabolic and nutritional disorders. As with other selective serotonin reuptake inhibitors, hyponatremia may occur in rare cases, which is reversed after discontinuation of fluvoxamine. Some cases were caused by the syndrome of insufficient secretion of antidiuretic hormone. Most of these cases were observed in elderly patients.

Blood glucose control may be impaired (i. e. hyperglycemia, hypoglycemia, impaired glucose tolerance), especially in the early stages of treatment. If fluvoxamine is prescribed to patients with a history of diabetes mellitus, it may be necessary to adjust the dose of antidiabetic drugs.

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

Hematological abnormalities Intradermal hemorrhages such as ecchymosis and purpura have been reported, as well as hemorrhagic manifestations (e. g. gastrointestinal bleeding) observed with the use of selective serotonin reuptake inhibitors. Caution should be exercised when prescribing these medications in elderly patients and patients receiving concomitant medications that affect platelet function (for example, atypical antipsychotics and phenothiazines, many tricyclic antidepressants, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs) or drugs that increase the risk of bleeding, as well as in patients with a history of bleeding or prone to bleeding (for example, with thrombocytopenia).

Increased risk of QT prolongation/paroxysmal ventricular tachycardia of the “pirouette” type in combination therapy with 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 administered together with these drugs.

Fluvoxamine may cause a slight decrease in heart rate (by 2-6 beats per minute).

Withdrawal Reactionswhen discontinuing fluvoxamine, withdrawal symptoms may occur, although available data from preclinical and clinical studies have not shown any dependence on fluvoxamine treatment. Symptoms noted in case of drug withdrawal: dizziness, paresthesia, headache, nausea, anxiety. Most of these symptoms are mild in nature and stop on their own. When stopping treatment with the drug, it is recommended to gradually reduce the dose.

Ability to drive a car and use machines and mechanisms. Fevarin, given 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, drowsiness has been reported during treatment with fluvoxamine. Therefore, it is recommended to exercise caution until the final determination of the individual response to the drug.

Form of production

Coated tablets 50,100 mg: 15 or 20 tablets in a PVC/PVDC / Al blister. 1,2,3 or 4 blisters in a cardboard box together with the instructions for use.

Storage conditions

List B. In the original packaging, in a dry place protected from light at a temperature not exceeding 25°C. Keep out of reach of children!

Shelf

life is 3 years. The drug should not be used after the expiration date.

Active ingredient

Fluvoxamine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Indications

Obsessive-compulsive disorder, Depression