Fevarin, 100 mg 30 pcs.

Obsessive Compulsive Disorder, DepressionTreatment and Prevention of Depression, Treatment of Obsessive Compulsive Disorder Symptoms

Indications

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

Pharmacological effect

Pharmacotherapeutic group: antidepressant.

Special instructions

As with the use of other psychotropic drugs, it is not recommended to consume alcohol during treatment with Fevarin®.

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

Increased risk of suicide in the early stages of recovery is widespread in clinical practice.

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

Patients with a history of suicidal events or a significant degree of suicidal ideation are known to be at greater risk of suicidal ideation or behavior before treatment and should be closely 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 for any clinical deterioration, suicidal behavior or thoughts, or unusual changes in behavior, and to immediately seek professional advice if such symptoms occur.

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 the 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 often in patients receiving an antidepressant compared to those receiving placebo. If a treatment decision is made based on clinical need, the patient should be closely monitored for the emergence of suicidal symptoms.

Additionally, long-term safety data for children and adolescents regarding growth, development, and cognitive development are lacking.

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

Elderly patients
Data obtained from the treatment of elderly patients and younger patients indicate that there are no clinically significant differences between the daily doses usually used in them. However, dose increases in elderly patients should always be done more slowly and with greater caution.

Akathisia/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 liver or kidney failure should begin with low doses and such patients should be under strict medical supervision. In rare cases, treatment with fluvoxamine may lead to an increase in the activity of liver enzymes, most often accompanied by corresponding 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 serotonergic syndrome or a condition similar to neuroleptic malignant syndrome have been described, which may be associated with the use of fluvoxamine, especially in combination with other serotonergic and/or neuroleptic drugs. Because these syndromes can lead to potentially life-threatening conditions manifested by 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 the point of delirium or coma – in such cases, treatment with fluvoxamine should be discontinued and should be appropriate symptomatic treatment was started.

Metabolic and nutritional disorders.
As with the use of other selective serotonin reuptake inhibitors, in rare cases hyponatremia may occur, which reverses after discontinuation of fluvoxamine. Some cases have been caused by antidiuretic hormone deficiency syndrome. These cases were mainly observed in elderly patients.

Blood glucose control may be impaired (ie, hyperglycemia, hypoglycemia, impaired glucose tolerance), especially early in treatment. If fluvoxamine is prescribed to patients with a history of diabetes mellitus, dosage adjustment of antidiabetic drugs may be required.

The most commonly 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 disorders
There are reports of intradermal hemorrhages such as ecchymosis 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 concomitantly receiving drugs that affect 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 bleeding proneness (for example, with thrombocytopenia).

Cardiac disorders
Increased risk of prolongation of the QT interval/paroxysmal ventricular tachycardia of the “pirouette” type during combination therapy of fluvoxamine with terfenadine or astemizole or cisapride, due to an increase in the concentration of the latter in the blood plasma. Therefore, fluvoxamine should not be coadministered with these drugs.

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

Withdrawal reactions
When you stop taking fluvoxamine, withdrawal symptoms may develop, although available data from preclinical and clinical studies have not shown dependence on fluvoxamine treatment. Symptoms noted in case of drug withdrawal: dizziness, paresthesia, headache, nausea, anxiety. Most of these symptoms are mild and self-limiting. When stopping treatment with the drug, a gradual dose reduction is recommended.

Ability to drive a car and use machines and mechanisms.
Fevarin, administered to healthy volunteers in doses up to 150 mg, had no or negligible effect on the ability to drive a car and control machines. At the same time, there are reports of drowsiness noted during treatment with fluvoxamine. Therefore, caution is recommended until the individual response to the drug is definitively determined.

Active ingredient

Fluvoxamine

Composition

Active substance:

fluvoxamine maleate – 100 mg

excipients:

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 (E171) – 2.1 mg.

Pregnancy

Small observational data 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 prescribed to pregnant women with caution.

Isolated cases of withdrawal syndrome in newborns have been described following the use of fluvoxamine late in pregnancy.

Some neonates exposed to selective serotonin reuptake inhibitors in the third trimester of pregnancy experienced feeding and/or breathing difficulties, seizure disorders, unstable body temperature, hypoglycemia, tremors, abnormal muscle tone, hyperexcitability 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 liver dysfunction, simultaneous use of MAO inhibitors, children under 8 years of age, hypersensitivity to fluvoxamine.

Side Effects

Some side effects observed in clinical trials were often related to symptoms of depression rather than to 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.

Uncommon (>0.1% and
Vascular disorders: orthostatic hypotension
Musculoskeletal and connective tissue disorders: arthralgia, myalgia.
Nervous system disorders: ataxia, extrapyramidal disorders.
Mental disorders: state of confusion, hallucinations.
Disorders of the genital organs and mammary gland: disturbance (delay) of ejaculation.
Skin and subcutaneous tissue disorders: skin hypersensitivity reactions (including rash, itching, angioedema).

Rare (>0.01% and
Liver disorders: impaired liver function (increased activity of liver enzymes).
Nervous system disorders: seizures.
Mental disorders: mania
Genital and breast disorders: galactorrhea.
Skin and subcutaneous tissue disorders: photosensitivity reactions.

In addition to the adverse events described during clinical trials, the following adverse effects have been reported during post-marketing use of fluvoxamine. The exact frequency cannot be provided and is therefore classified as “unknown”.

Blood and lymphatic system disorders: hemorrhages (eg, 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; neuroleptic malignant syndrome-like; akathisia/psychomotor agitation; paresthesia; dysgeusia.

Mental disorders: Cases of suicidal thoughts and suicidal behavior have been reported during treatment with fluvoxamine or shortly after its termination.

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

Disorders of the genital organs and breast: anorgasmia.

General disorders: drug withdrawal syndrome, including withdrawal syndrome in newborns.

Interaction

Fluvoxamine should not be used in combination with MAO inhibitors (see section “Contraindications”).
Fluvoxamine significantly inhibits the cytochrome P450 1A2 isoenzyme and, to a lesser extent, the P450 2C and P 450 3A4 isoenzymes. Drugs that are extensively metabolized by these isoenzymes are eliminated more slowly and may have higher plasma concentrations when coadministered with fluvoxamine. This is especially important for drugs that have a narrow therapeutic range. Patients require careful monitoring, and if necessary, it is recommended to adjust the dose of these drugs.

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

Isoenzyme cytochrome P450 1A2
With simultaneous use of fluvoxamine, an increase in the concentration of tricyclic antidepressants (clomipramine, imipramine, amitriptyline) and antipsychotics (clozapine, olanzapine), which are largely metabolized by the cytochrome P450 1A2 isoenzyme, was observed. Therefore, if treatment with fluvoxamine is initiated, a dose reduction of these drugs should be considered.

Patients concomitantly taking fluvoxamine and drugs with a narrow therapeutic range of action metabolized by the cytochrome P450 1A2 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 observed. In this regard, it is possible to recommend reducing the dose of propranolol in case of simultaneous use with fluvoxamine. Plasma concentrations of caffeine may increase while taking fluvoxamine. Therefore, patients who consume large amounts of caffeine-containing beverages should reduce their consumption while taking fluvoxamine and when adverse effects of caffeine, such as tremor, palpitations, nausea, restlessness, and insomnia, are observed.

Concomitant use of fluvoxamine and ropinirole may increase the plasma concentration of ropinirole, thereby increasing the risk of overdose. In such cases, monitoring or, if necessary, dose reduction or discontinuation of ropinirole during treatment with fluvoxamine is recommended.

Isoenzyme cytochrome P450 2 C

Patients concomitantly taking fluvoxamine and drugs with a narrow therapeutic range of action that are metabolized by the cytochrome P450 2C isoenzyme (such as phenytoin) should be closely monitored, and dosage adjustment of these drugs is recommended if necessary.

When fluvoxamine was used in combination with warfarin, a significant increase in plasma warfarin concentrations and prolongation of prothrombin time were observed.

Isoenzyme cytochrome P450 ZA4

Terfenadine, astemizole, cisapride: When combined with fluvoxamine, plasma concentrations of terfenadine, astemizole or cisapride may increase, increasing the risk of QT prolongation/torsade de pointes (TdP). Therefore, fluvoxamine should not be coadministered with these drugs.

Patients simultaneously taking fluvoxamine and drugs with a narrow therapeutic range of action that are metabolized by the cytochrome P450 3A4 isoenzyme (such as carbamazepine, cyclosporine) should be closely monitored, and dose adjustment of these drugs is recommended.

When administered concomitantly with fluvoxamine, benzodiazepines that undergo 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

Fluvoxamine has no effect on plasma digoxin concentrations.

Renal excretion

Fluvoxamine has no effect on plasma concentrations of atenolol.

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 be enhanced (see “Special Instructions”). Fluvoxamine has been used in combination with lithium drugs to treat severely ill patients who respond poorly to pharmacotherapy. It should be noted that lithium (and possibly also tryptophan) enhances the serotonergic effects of the drug, and therefore this type of combination pharmacotherapy should be carried out with caution.

When taking oral anticoagulants and fluvoxamine simultaneously, the risk of hemorrhage may increase.

Such patients should be under medical supervision.

Overdose

Symptoms

The most typical symptoms include gastrointestinal disturbances (nausea, vomiting and diarrhea), drowsiness and dizziness. In addition, there are reports of violations. cardiac activity (tachycardia, bradycardia, arterial hypotension), liver dysfunction, seizures and coma.

Fluvoxamine has a wide therapeutic dose range with regard to the safety of overdose. Since marketing, reports of deaths attributed to overdose with 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 have been 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 soon as possible after taking the drug, as well as symptomatic treatment. In addition, repeated intake of activated carbon is recommended, and, if necessary, the appointment of osmotic laxatives. Forced diuresis or dialysis are not effective.

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 the reach of children!

Shelf life

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

Manufacturer

Mylan Laboratories SAS, France