Fluvoxamine-SZ (Tablets) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda NAO (Russia)

Contact Information

SEVERNAYA ZVEZDA NAO (Russia)

ATC Code

N06AB08 (Fluvoxamine)

Active Substance

Fluvoxamine (Rec.INN registered by WHO)

Dosage Forms

	Fluvoxamine-SZ	Film-coated tablets, 50 mg: 20, 30 or 60 pcs.
		Film-coated tablets, 100 mg: 20, 30 or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with a score on one side; the core of the tablet on the cross-section is white or almost white; the tablet can be divided into equal doses.

Excipients: mannitol, anhydrous lactose (lactopress anhydrous) (milk sugar), corn starch, pregelatinized starch, colloidal silicon dioxide (aerosil), sodium stearyl fumarate.

Shell composition polyvinyl alcohol, polysorbate-80 (tween-80), talc, titanium dioxide (E171).

10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
30 pcs. – polymer bottles (1) – cardboard packs.

Film-coated tablets white or almost white, round, biconvex, with a score on one side; the core of the tablet on the cross-section is white or almost white; the tablet can be divided into equal doses.

Excipients: mannitol, anhydrous lactose (lactopress anhydrous) (milk sugar), corn starch, pregelatinized starch, colloidal silicon dioxide (aerosil), sodium stearyl fumarate.

Shell composition polyvinyl alcohol, polysorbate-80 (tween-80), talc, titanium dioxide (E171).

10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
30 pcs. – polymer bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Psychoanaleptics, antidepressants; selective serotonin reuptake inhibitors

Pharmacological Action

Receptor binding studies have shown that Fluvoxamine is a potent inhibitor of serotonin reuptake both in vitro and in vivo with minimal affinity for serotonin receptors. Its ability to bind to α- and β-adrenergic receptors, histamine, m-cholinergic or dopamine receptors is negligible.

Fluvoxamine at therapeutic doses has a high affinity for δ₁ receptors, acting as their agonist.

Pharmacokinetics

Absorption

After oral administration, Fluvoxamine is completely absorbed from the gastrointestinal tract. C_max of fluvoxamine in blood plasma is noted 3-8 hours after administration. The absolute bioavailability is 53% after primary metabolism in the liver. Concurrent administration of fluvoxamine with food does not affect pharmacokinetics.

Distribution

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

Metabolism

The metabolism of fluvoxamine occurs mainly in the liver. Although cytochrome P450 isoenzyme 2D6 is the main one in the metabolism of fluvoxamine, the concentration of fluvoxamine in the blood plasma of individuals with reduced function of this isoenzyme is not much higher than in individuals with normal metabolism.

Fluvoxamine undergoes biotransformation in the liver (mainly by oxidative demethylation) to at least 9 metabolites, which are excreted by the kidneys. The two main metabolites have negligible pharmacological activity. Other metabolites are probably pharmacologically inactive.

Fluvoxamine significantly inhibits cytochrome P450 1A2 and P450 2C19, moderately inhibits cytochromes P450 2C9, P450 2D6 and P450 3A4.

Excretion

The mean T_1/2 from blood plasma, which is 13-15 hours for a single dose, increases slightly with repeated administration (17-22 hours), and C_ss in blood plasma is usually reached within 10-14 days.

Linearity/non-linearity

The pharmacokinetics of a single dose of fluvoxamine is linear. C_ss of fluvoxamine is higher than the single dose concentration, and this disproportionality is more pronounced at higher daily doses.

Special patient groups

The pharmacokinetics of fluvoxamine are the same in healthy individuals, the elderly, or patients with renal failure. The metabolism of fluvoxamine is reduced in patients with liver disease.

Children

C_ss of fluvoxamine in blood plasma is twice as high in children (aged 6-11 years) than in adolescents (aged 12-17 years). Fluvoxamine plasma concentrations in adolescents are similar to those in adults.

Indications

Adults aged 18 years and older for

• Depressions of various origins;
• Obsessive-compulsive disorders.

Children aged 8 years and older and adolescents for

• Obsessive-compulsive disorders.

ICD codes

Dosage Regimen

Orally, without chewing, with water. The tablet can be divided into equal doses.

Before starting treatment with Fluvoxamine-SZ, the strategy for discontinuing the drug should be discussed with patients to minimize withdrawal syndrome (see section “Special Precautions”).

Adults

Depressions

The recommended initial dose for adults is 50 or 100 mg once/day, in the evening.

After 3-4 weeks from the start of therapy, the dose should be reviewed and adjusted according to the clinical experience with the drug. A gradual increase in dose to an effective level is recommended.

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 above 150 mg are recommended to be divided into 2 or 3 doses. The selection of the minimum effective maintenance dose should be carried out carefully on an individual basis.

In accordance with official WHO recommendations, antidepressant treatment should be continued for at least 6 months of remission after a depressive episode.

For prevention of depression relapse, it is recommended to take 100 mg of Fluvoxamine-SZ once/day, daily.

Obsessive-compulsive disorders (OCD)

The recommended initial dose for adults is 50 mg/day for 3-4 days.

The effective daily dose is usually from 100 to 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 above 150 mg are recommended to be divided into 2 or 3 doses.

With a good therapeutic response to the drug, treatment can be continued using an individually selected daily dose. If improvement is not achieved after 10 weeks, treatment with fluvoxamine should be reconsidered. To date, no systematic studies have been organized that could answer the question of how long treatment with fluvoxamine can be carried out, however, obsessive-compulsive disorders are chronic, and therefore it may be considered appropriate to extend treatment with fluvoxamine beyond 10 weeks in patients who have responded well to this drug. The selection of the minimum effective maintenance dose should be carried out carefully on an individual basis. The need for treatment should be periodically reassessed. Some clinicians recommend concomitant psychotherapy in patients who have responded well to pharmacotherapy. Long-term efficacy (more than 24 weeks) has not been confirmed.

Withdrawal syndrome after discontinuation of fluvoxamine

Abrupt discontinuation of the drug should be avoided. When discontinuing treatment with fluvoxamine, the dose should be gradually reduced over a period of at least 1-2 weeks to reduce the risk of withdrawal syndrome (see sections “Dosage Regimen” and “Adverse Reactions”). If intolerable symptoms occur after dose reduction or after discontinuation of treatment, resumption of treatment at the previously recommended dose may be considered. Later, the physician may again begin to reduce the dose, but more gradually.

Special patient groups

Patients with impaired liver/kidney function

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

Children

Depressions

Due to lack of clinical experience, Fluvoxamine is contraindicated for the treatment of depression in children under 18 years of age.

Obsessive-compulsive disorders

Children over 8 years of age and adolescents

In children over 8 years of age and adolescents, data on use in doses above 100 mg twice/day for 10 weeks are limited. The initial dose for children over 8 years of age and adolescents is 25 mg/day in a single dose, preferably at bedtime. The dose should be increased by 25 mg, taking into account tolerability, every 4-7 days until the effective daily dose is reached.

The effective dose is usually from 50 to 200 mg/day, the maximum dose in children should not exceed 200 mg/day. Daily doses above 50 mg are recommended to be divided into 2 doses, and if the resulting 2 doses are not equal, the larger dose should be taken at bedtime.

Adverse Reactions

Adverse reactions observed in clinical trials, with the frequency indicated below, were often associated with the disease rather than with the treatment.

Tabulated summary of adverse reactions

All adverse reactions are distributed by organ systems and frequency of occurrence: common (≥1/100, but <1/10); uncommon (≥1/1000, but <1/100); rare (≥1/10000, but <1/1000); very rare (<1/10000), frequency unknown (cannot be estimated from available data).

* Nausea, sometimes accompanied by vomiting, is the most frequently observed adverse reaction associated with fluvoxamine treatment. The frequency of manifestation usually decreases during the first 2 weeks of drug use.

** Epidemiological studies, conducted mainly in patients aged ≥50 years, have shown an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism of the increased risk is unknown.

*** This adverse event has been registered as a class effect for drugs of the SSRI/SNRI groups (see section “Use in Pregnancy and Lactation”).

Description of selected adverse reactions

Withdrawal syndrome after discontinuation of fluvoxamine

Discontinuation of fluvoxamine (especially abrupt) often leads to the development of withdrawal syndrome. The most common symptoms noted upon drug withdrawal: dizziness, sensory disturbances (including paresthesia, visual disturbances, and electric shock sensation), sleep disorders (including insomnia and vivid dreams), agitation, irritability, confusion, emotional lability, headache, nausea and/or vomiting, diarrhea, sweating, palpitations, tremor, and anxiety (see section “Special Precautions”).

Most of these symptoms are mild or moderate and resolve on their own, but in some patients they can be severe and/or prolonged. For this reason, if treatment with fluvoxamine is no longer required, it is recommended to gradually reduce the dose until complete discontinuation of the drug (see sections “Dosage Regimen” and “Special Precautions”).

Children

In a 10-week placebo-controlled study in children and adolescents with obsessive-compulsive disorders, adverse reactions such as insomnia, asthenia, hyperexcitability, hyperkinesia, drowsiness, and dyspepsia were more common in patients receiving the drug compared to patients receiving placebo. Serious adverse reactions in this study included hyperexcitability and hypomania.

Seizures in children and adolescents have been reported outside of clinical trials.

Contraindications

• Hypersensitivity to fluvoxamine or to any of the excipients included in the drug;
• Concomitant use with tizanidine and MAO inhibitors (see section “Drug Interactions”):
  • Treatment with fluvoxamine can be started 2 weeks after discontinuation of an irreversible MAO inhibitor;
  • The day after discontinuation of a reversible MAO inhibitor (e.g., moclobemide, linezolid).

The time interval between discontinuation of fluvoxamine and initiation of therapy with any MAO inhibitors should be at least 1 week.

• Concomitant use with pimozide and ramelteon preparations (see section “Drug Interactions”);
• Age under 18 years for the treatment of depression of various origins;
• Age under 8 years for the treatment of obsessive-compulsive disorders.

With caution

Hepatic and renal insufficiency, history of seizures, epilepsy, elderly age, patients with a tendency to bleeding (thrombocytopenia), pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Pregnancy

Epidemiological data suggest that the use of SSRIs during pregnancy, especially in the last months of pregnancy, may increase the risk of persistent pulmonary hypertension (PPHN) in newborns. Available data indicate that PPHN occurs in approximately 5 cases per 1000 births (compared to 1-2 cases per 1000 births if the mother did not use SSRIs in late pregnancy).

The use of fluvoxamine during pregnancy is not recommended, except in cases where the woman’s clinical condition indicates the need for its use.

Isolated cases of withdrawal syndrome in newborns after the use of fluvoxamine at the end of pregnancy have been described.

Some newborns exposed to SSRIs in the third trimester of pregnancy experienced feeding and/or breathing difficulties, seizure disorders, unstable body temperature, hypoglycemia, tremor, muscle tone disorders, hyperreflexia syndrome, cyanosis, irritability, lethargy, drowsiness, vomiting, difficulty falling asleep, and continuous crying, which may have required prolonged hospitalization.

Observational data indicate an increased (less than 2-fold) risk of postpartum hemorrhage after the use of SSRI/SNRI group drugs within one month before delivery.

Breastfeeding

Fluvoxamine passes into breast milk in small amounts. In this regard, the drug should not be used during breastfeeding.

Fertility

Reproductive toxicity studies in animals have shown that Fluvoxamine affects the reproductive function of males and females, increases the risk of intrauterine fetal death and reduces fetal body weight at doses exceeding the maximum recommended human doses by approximately 2 times. In addition, an increase in the frequency of perinatal mortality of offspring was observed in pre- and postnatal studies. The significance of these data for humans is unknown.

Fluvoxamine should not be prescribed to patients planning pregnancy, except in cases where the patient’s clinical condition requires the prescription of fluvoxamine.

Use in Hepatic Impairment

Treatment of patients with hepatic insufficiency should be started with low doses under strict medical supervision.

Use in Renal Impairment

Treatment of patients with renal insufficiency should be started with low doses under strict medical supervision.

Pediatric Use

Due to lack of clinical experience, Fluvoxamine is contraindicated for the treatment of depression in children under 18 years of age.

Children aged 8 years and older and adolescents are prescribed for obsessive-compulsive disorders.

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide attempts (suicidal behavior). This risk persists until significant improvement occurs. Since improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until such improvement occurs. In clinical practice, the risk of suicide may increase in the early stages of recovery.

Other mental disorders for which Fluvoxamine is prescribed may also be associated with an increased risk of suicidal actions. In addition, these conditions may accompany depression. Therefore, patients with other mental disorders should be closely monitored.

Patients with a history of suicidal behavior or those who exhibit significant suicidal thinking prior to initiation of treatment are known to be at greater risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment.

Close 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) must be warned about the need to monitor for any clinical worsening, suicidal behavior or suicidal thoughts, unusual changes in behavior, and to immediately seek specialist consultation if such symptoms appear.

Adults (18 to 24 years)

A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders revealed an increased risk of suicidal behavior with antidepressants compared to placebo in patients younger than 25 years.

Elderly patients

Data from the treatment of elderly patients and younger patients indicate no clinically significant differences between the daily doses typically used in them. Nevertheless, dose increases in elderly patients should always be performed more slowly and with caution.

Akathisia/Psychomotor agitation

The development of akathisia associated with fluvoxamine intake is characterized by subjectively unpleasant and distressing restlessness. The need to move is 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 in patients with such symptoms may worsen their condition.

Renal and hepatic impairment

Treatment of patients suffering from hepatic or renal impairment should be initiated with low doses, and such patients must be under strict medical supervision. In rare cases, treatment with fluvoxamine may lead to increased activity of liver enzymes, most often accompanied by corresponding clinical symptoms; in such cases, the drug Fluvoxamine-SZ should be discontinued.

Nervous system disorders

Although animal studies have not revealed proconvulsant properties of fluvoxamine, caution is necessary when prescribing the drug to patients with a history of seizures. Prescribing fluvoxamine should be avoided in patients with unstable epilepsy, and patients with stable epilepsy should be under close supervision. Treatment with Fluvoxamine-SZ should be discontinued if epileptic seizures occur or their frequency increases.

Rare cases of serotonin syndrome or a condition resembling neuroleptic malignant syndrome (NMS) have been described, which may be associated with the intake of fluvoxamine, especially in combination with other serotonergic and/or neuroleptic medicinal products, or in combination with buprenorphine, or buprenorphine/naloxone. Symptoms of serotonin syndrome may include changes in mental status, autonomic nervous system instability, neuromuscular disorders, and/or gastrointestinal symptoms. Since these syndromes can lead to potentially life-threatening conditions manifested by hyperthermia, muscle rigidity, myoclonus, autonomic instability with possible rapid changes in vital parameters, changes in mental status including confusion, irritability, extreme agitation progressing to delirium or coma – in such cases, treatment with fluvoxamine should be discontinued and appropriate symptomatic treatment initiated.

Metabolism and nutrition disorders

As with the use of other SSRIs, in rare cases, hyponatremia may occur, which is reversible after discontinuation of fluvoxamine. Some cases were caused by the syndrome of inappropriate antidiuretic hormone secretion. These cases were mainly 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, adjustment of the dose of antidiabetic drugs may be required.

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

Eye disorders

Cases of mydriasis have been reported with the use of SSRIs, such as Fluvoxamine. Therefore, Fluvoxamine should be prescribed with caution to patients with increased intraocular pressure or patients at high risk of acute angle-closure glaucoma.

Hematological disorders

There are reports of such intradermal hemorrhages as ecchymoses and purpura, as well as other hemorrhagic manifestations (e.g., gastrointestinal bleeding or gynecological/postpartum bleeding) observed with the use of SSRIs. Caution is necessary when prescribing these medicinal products to elderly patients and patients concurrently receiving drugs that affect platelet function (e.g., 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 patients with a history of bleeding or those prone to bleeding (e.g., with thrombocytopenia or coagulation disorders).

Intake of drugs from the SSRI, SNRI groups may increase the risk of postpartum bleeding (see sections “Pregnancy and lactation” and “Adverse reactions”).

Cardiac disorders

An increased risk of QT interval prolongation on the electrocardiogram (ECG) and the risk of paroxysmal ventricular tachycardia of the “torsades de pointes” type was noted with combined therapy of fluvoxamine with terfenadine or astemizole, or cisapride, due to an increase in the plasma concentrations of the latter. Therefore, Fluvoxamine should not be prescribed together with these drugs. Fluvoxamine may cause a slight decrease in heart rate (by 2-6 beats per minute).

Electroconvulsive therapy (ECT)

Experience with the clinical use of fluvoxamine during ECT is limited, so such therapy should be conducted with caution.

Discontinuation syndrome

Upon discontinuation of fluvoxamine intake, a withdrawal syndrome may develop, although available data from preclinical and clinical studies have not revealed dependence on fluvoxamine treatment. The most frequent symptoms noted in case of drug discontinuation are: dizziness, sensory disturbances (including paresthesia, visual disturbances, and electric shock sensation), sleep disorders (including insomnia and vivid dreams), agitation, irritability, confusion, emotional lability, headache, nausea and/or vomiting, diarrhea, sweating, palpitations, tremor, and anxiety (see section “Adverse reactions”).

Most of these symptoms are mild or moderate in severity and resolve spontaneously, but in some patients they may be severe and/or prolonged. Such symptoms usually occur within the first few days after treatment discontinuation. For this reason, it is recommended to gradually reduce the dose of fluvoxamine before complete discontinuation in accordance with the patient’s condition (see section “Dosage regimen”).

Mania/Hypomania

Fluvoxamine should be used with caution in patients with a history of mania/hypomania. If a patient develops a manic phase, the use of fluvoxamine should be discontinued.

Sexual dysfunction

SSRIs may cause symptoms of sexual dysfunction (see section “Adverse reactions”). Reports have been received of persistent sexual dysfunction, the symptoms of which persisted despite discontinuation of the SSRI.

Children

Fluvoxamine should not be used for the treatment of children and adolescents under 18 years of age, except for patients with obsessive-compulsive disorders. Due to lack of clinical experience, Fluvoxamine should not be used to treat depression in children. In clinical studies conducted among children and adolescents, suicide-related behavior (suicide attempts and thoughts) and hostility (primarily aggression, oppositional behavior, and anger) were observed more frequently in patients receiving the antidepressant compared to those receiving placebo. If, based on clinical need, a decision for treatment is made, the patient must be closely monitored for the emergence of suicidal symptoms.

Furthermore, long-term safety data for children and adolescents concerning growth, maturation, and cognitive and behavioral development are lacking.

Excipients

The drug Fluvoxamine-SZ contains anhydrous lactose (lactopress anhydrous) (milk sugar). Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

The drug Fluvoxamine-SZ contains mannitol, which may have a mild laxative effect.

The drug Fluvoxamine-SZ contains less than 1 mmol (23 mg) of sodium per tablet, i.e., it is essentially sodium-free.

Effect on the ability to drive vehicles and operate machinery

Fluvoxamine in doses up to 150 mg has no or negligible influence on the ability to drive vehicles and operate machinery. At the same time, there are reports of drowsiness noted during treatment with fluvoxamine. In this regard, it is recommended to exercise caution until the individual response to the drug is definitively determined.

Overdose

Symptoms

The most characteristic symptoms include gastrointestinal disorders (nausea, vomiting, and diarrhea), drowsiness, and dizziness. In addition, there are reports of cardiac disorders (tachycardia, bradycardia, arterial hypotension), impaired liver function, seizures, and coma.

Fluvoxamine has a wide therapeutic index regarding the risk of overdose. Since its market release, reports of fatalities attributed to fluvoxamine overdose alone have been extremely rare. The highest recorded dose of fluvoxamine taken by a single patient was 12 g. This patient recovered completely. More serious complications were observed in cases of intentional fluvoxamine overdose in combination with other drugs.

Treatment

There is no specific antidote for fluvoxamine. In case of overdose, gastric lavage is recommended, which should be performed as early as possible after drug intake, as well as symptomatic treatment. Furthermore, multiple doses of adsorbents (e.g., activated charcoal) are recommended, and osmotic laxatives may be prescribed if necessary. Forced diuresis or dialysis is not effective.

Drug Interactions

MAO inhibitors

Fluvoxamine must not be used in combination with MAO inhibitors, including linezolid, due to the risk of developing serotonin syndrome (see section “Contraindications”).

Effect of fluvoxamine on the oxidative metabolism of other drugs

Fluvoxamine may inhibit the metabolism of drugs that are biotransformed by certain cytochrome P450 isoenzymes. In vitro and in vivo studies have shown a potent inhibitory effect of fluvoxamine on cytochrome P450 1A2 and P450 2C19 isoenzymes and, to a lesser extent, on cytochrome P450 2C9, P450 2D6, and P450 3A4 isoenzymes.

Drugs that are significantly metabolized by these isoenzymes, when used concomitantly with fluvoxamine, may have higher plasma concentrations of the active substance or, in the case of prodrugs such as clopidogrel, lower concentrations of the active metabolite. Such drugs should be prescribed at the minimum dose or the dose should be reduced to the minimum when used concomitantly with fluvoxamine. Careful monitoring of plasma concentrations, effects, or adverse reactions, and dose adjustment of these drugs is required if necessary. This is particularly significant for drugs that have a narrow therapeutic index.

Ramelteon

When fluvoxamine was taken twice daily at 100 mg for 3 days before simultaneous single administration of ramelteon at a dose of 16 mg, the AUC value for ramelteon increased approximately 190-fold, and the C_max value increased approximately 70-fold compared to these parameters when ramelteon was administered alone.

Drugs with a narrow therapeutic index

Patients concurrently taking Fluvoxamine and drugs with a narrow therapeutic index undergoing biotransformation by one or more cytochrome isoenzymes inhibited by Fluvoxamine (such as tacrine, theophylline, methadone, mexiletine, phenytoin, carbamazepine, and cyclosporine) must be under close observation. If necessary, dose adjustment of these drugs is recommended.

Given the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, concomitant use of pimozide and fluvoxamine is contraindicated (see section “Contraindications”).

Tricyclic antidepressants and antipsychotics

During concomitant use of fluvoxamine, an increase in plasma concentrations of tricyclic antidepressants (e.g., clomipramine, imipramine, amitriptyline) and antipsychotics (e.g., clozapine, olanzapine, quetiapine), which are significantly biotransformed by the cytochrome P450 1A2 isoenzyme, has been observed. In this regard, if treatment with fluvoxamine is initiated, a reduction in the dose of these drugs should be considered.

Benzodiazepines

When benzodiazepines undergoing oxidative metabolism, such as triazolam, midazolam, alprazolam, and diazepam, are used concomitantly with fluvoxamine, an increase in their plasma concentrations is possible. The dose of these benzodiazepines should be reduced during the period of fluvoxamine intake.

Cases of increased plasma concentration

When fluvoxamine and ropinirole are used concomitantly, the plasma concentration of ropinirole may increase, thus increasing the risk of overdose. In such cases, monitoring of ropinirole concentration or, if necessary, reducing its dose during the period of fluvoxamine treatment and after its discontinuation is recommended.

During the interaction of fluvoxamine with propranolol, an increase in propranolol plasma concentrations was noted. In this regard, a reduction in the propranolol dose can be recommended in case of concomitant use with fluvoxamine.

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

Cases of increased frequency of adverse reactions

Isolated cases of cardiotoxicity have been reported with the concomitant use of fluvoxamine and thioridazine.

During fluvoxamine intake, plasma caffeine concentration may increase. Thus, patients who consume large amounts of caffeine-containing beverages should reduce their consumption during the period of fluvoxamine intake if adverse effects of caffeine are observed, such as tremor, palpitations, nausea, anxiety, insomnia.

Cytochrome P450 3A4 isoenzyme

Terfenadine, astemizole, cisapride, sildenafil: during combined therapy with fluvoxamine, plasma concentrations of terfenadine, astemizole, or cisapride may increase, increasing the risk of QT interval prolongation on the ECG and the risk of paroxysmal ventricular tachycardia of the “torsades de pointes” type. Therefore, Fluvoxamine should not be prescribed together with these drugs.

Glucuronidation

Fluvoxamine does not affect the plasma concentration of digoxin.

Renal excretion

Fluvoxamine does not affect the plasma concentration of atenolol.

Pharmacodynamic interactions

In case of concomitant use of fluvoxamine with serotonergic drugs (such as triptans, tramadol, buprenorphine, buprenorphine/naloxone, selective serotonin reuptake inhibitors (SSRIs) and St. John’s wort preparations), the serotonergic effects of fluvoxamine may be enhanced, which can lead to an increased risk of serotonin syndrome, a potentially life-threatening condition (see section “Special warnings and precautions for use”).

Fluvoxamine has been used in combination with lithium preparations for the treatment of 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 kind of combined pharmacotherapy should be conducted with caution.

When indirect anticoagulants and fluvoxamine are used concomitantly, the risk of hemorrhages may increase. Such patients should be under medical supervision.

As with the use of other psychotropic drugs, patients during treatment with fluvoxamine should refrain from consuming alcohol.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.