Fluvoxamine

Chemical properties

serotonin reuptake inhibitors . The antidepressant is synthesized in the form of a white or white with various shades of odorless crystalline powder. The product is highly soluble in chloroform and ethylene , poorly soluble in water, and practically insoluble in ethers . The substance has lipophilic properties. Molecular weight of the compound = 318.3 grams per mole.

The pharmacological activity of the drug is similar to Fluoxetine , however, the effect of taking Fluvoxamine develops faster.

The medicine is usually released in the form of tablets, dosage of 100 or 50 mg.

Pharmacodynamics and pharmacokinetics

Fluvoxamine has the ability to selectively inhibit the reuptake of serotonin by neurons from the synaptic cleft by blocking the membrane pump of the presynaptic biological membrane. The substance enhances serotonergic transmission and reduces the overall circulation of serotonin , its concentration in the synapse increases significantly. It also blocks the reuptake of the neurotransmitter serotonin in platelets . The drug has a slight effect on the processes of reuptake of norepinephrine and dopamine . The medicine does not affect the functioning of m-cholinergic , 5HT1 and 5PT2 receptors , histaminergic , beta and alpha adrenergic , dopaminergic receptors . The substance is better tolerated than similar drugs Amitriptyline and Imipramine .

After penetration into the gastrointestinal tract, the drug is well absorbed and absorbed through the walls of the stomach. Its bioavailability does not depend on the contents of the stomach and is approximately 53%. This level of bioavailability is due to the “first pass” effect of the substance through the liver.

When taking the drug systematically for 10 days, its equilibrium concentration is established after approximately 7 days. The substance reaches its maximum concentration in blood plasma within 3-8 hours.

About 80% of the drug binds to albumin in the blood plasma. Metabolism of the drug occurs in the liver, where 9 inactive metabolites are formed as a result of demethylation and deamination. The substance affects isoenzymes of the cytochrome P450 system , most actively on CYP1A2, CYP2C9 and CYP3A4.

The half-life of Fluvoxamine is 15 to 20 hours. About 95% is excreted via the kidneys, mainly in the form of metabolites (only 2.5% unchanged).

Studies have been conducted in patients with reduced renal clearance (from 5 to 45 ml per minute). In such patients, there was no accumulation of the substance in the body. In case of liver diseases, a slowdown in the processes of removing the drug from the body by approximately 30% was noted. In elderly patients, there was an increase in the maximum plasma concentration of the substance by 40% and an increase in the time of elimination from the body by 50%. The bioavailability of the substance in smoking patients also decreases, and the metabolism of the drug is induced.

The medicine is excreted in breast milk.

Contraindications

The product cannot be used:

• during lactation;
• for severe kidney and liver diseases;
• children under 8 years old;
• for diabetes mellitus ;
• if the patient has previously had epileptic seizures ;
• in pregnant women;
• if allergic to the active substance Fluvoxamine;
• during treatment with MAO inhibitors .

Please be careful:

• persons suffering from drug addiction;
• with mania ;
• for hypomania ;
• patients with a history myocardial infarction

Special patient groups

◊ Patients with kidney problems

Start with lower doses [1].

◊ Patients with liver disease

Reduce the dose - either take it less often, or reduce the dose by half [1].

◊ Patients with heart disease

Safe. Useful in recovery after a heart attack [1].

◊ Elderly patients

Lower doses are recommended for elderly patients [1].

◊ Children and teenagers

• Recommended for the treatment of OCD aged 8-17 years
• Initial dose: 25 mg at night, after 4-7 days increase to 50 mg. Maximum – 200 mg/day. Doses above 50 mg should be taken in two doses, with the larger portion taken at night [1].
• It is necessary to regularly and personally check the patient's condition, especially in the first weeks of treatment.
• Inform adults about the risks.

◊ Pregnant women

• There have been no adequate studies in pregnant women.
• Not recommended for pregnant women, especially in the first trimester
• All risks should be weighed and compared

◊ Breastfeeding

• The medicine passes into breast milk.
• If the infant shows signs of irritation or sedation, discontinue feeding or fluoxetine
• However, treatment after childbirth may be necessary, so the risks should be weighed.

Side effects

In controlled clinical trials conducted in America involving 1,087 patients with OCD and depression , about 22% stopped taking the medication due to adverse reactions.

During treatment with the drug, the following may occur:

• dizziness, asthenia , sleep disturbances, headache, drowsiness , agitation , anxiety and nervousness;
• anorexia, indigestion , nausea, dry mucous membranes of the oral cavity, pain in the abdomen, vomiting, diarrhea ;
• dyspnea , development of upper respiratory tract infections, yawning ;
• hyperstimulation of the central nervous system, distortion of taste, tremor , amblyopia ;
• palpitations, increased blood pressure , vasodilation ;
• increased sweating, flu-like syndrome , chills, trembling in the body;
• thinning of enamel and various damage to teeth, increased gas formation , constipation ;
• decreased libido , anorgasmia , dysuria , frequent urination, impaired ejaculation .

Indications

◊ Ministry of Health of Russia

F32 Depressive episode

F33 Recurrent depressive disorder

F42 Obsessive-compulsive disorder

◊ FDA recommendations

• Social anxiety
• OCD

◊ Recommendations from UK Medicines and Healthcare Products Regulatory Agency

• Major depressive episode
• OCD

◊ Using Off-label

• Bulimia
• PTSD
• Panic disorder [4]

Fluvoxamine, instructions for use (Method and dosage)

The dosage regimen is established by the attending physician depending on the disease and its severity.

At the initial stages of treatment, it is recommended to take 50-100 mg of the drug.

Further, the daily dosage can be increased to 200 mg. The maximum daily dosage of Fluvoxamine is 300 mg. When taking large doses of medication, it is recommended to distribute them over several doses.

The duration of treatment depends on many factors. However, after the patient is cured, he must take the medicine for another six months as a prophylaxis.

Treatment regimen

◊ Dosage and dose selection

• 100-300 mg/day for OCD, social anxiety
• 100-200 mg/day for depression
• Start with 50 mg, increase to 100 mg after 4-7 days, wait a few days to evaluate the effect. Can be increased every 4-7 days by 50 mg. Maximum – 300 mg/day.
• A dose below 100 mg is taken at night, a dose above 100 mg is divided into two doses, and a larger portion is taken at night [1].
• If anxiety, insomnia, agitation, or akathisia occur at the beginning of treatment or after interruption of treatment, the possibility of bipolar disorder should be considered and switched to a mood stabilizer or an atypical antipsychotic

◊ How quickly it works

• In some patients with anxiety and insomnia, the effect begins immediately.
• Begins to act after 2-4 weeks
• If there is no effect after 6-8 weeks, you need to increase the dose or switch to another drug
• To prevent relapse, it can be taken for many years.

◊ Expected result

• Complete remission.
• After the symptoms of depression disappear, you should continue taking it for 1 year if this was the treatment of the first episode. If this is to treat a recurrent episode, treatment can be extended indefinitely.
• Use in the treatment of anxiety can be indefinite [1].

◊ If it doesn't work

• Change the dose, switch to another medicine or add an auxiliary drug;
• Connect psychotherapy;
• Review the diagnosis by identifying comorbid conditions;
• In patients with undiagnosed bipolar affective disorder, the effectiveness of treatment may be low, in which case it is necessary to switch to a mood stabilizer [1].

◊ How to stop taking it

Gradually reduce to prevent withdrawal syndrome. Gradual reduction scheme: dose reduced by 50% - 3 days, again reduced by 50% - 3 days, complete cessation. If withdrawal symptoms appear, increase the dose, wait for withdrawal symptoms to subside, and continue decreasing [1].

◊ Treatment combinations

• For insomnia: trazadone
• For fatigue, drowsiness, loss of concentration: modafinil [3].
• Combinations with other antidepressants may activate bipolar disorder and suicidal ideation
• For bipolar depression, psychotic depression, treatment-resistant depression, treatment-resistant anxiety disorder: mood stabilizers, atypical antipsychotics
• For anxiety disorder: gabapentin, tiagabine
• In Europe and Japan, benzodiazepine and lithium augmentation is more commonly used for anxiety and depression.
• In the USA, augmentation with atypical antipsychotics, buspirone, and low doses of clomipramine is more often used in the treatment of OCD

Overdose

In case of an overdose of an antidepressant, may occur: drowsiness , nausea and vomiting, tachycardia or bradycardia , dizziness , dry mouth, severe decrease or increase in blood pressure , changes in the electrocardiogram , tremor , oliguria , myoclonus , coma , convulsions and seizures, increased levels of liver enzymes, hepatic failure. In medical practice, fatal overdoses of Fluvoxamine have been described.

The victim must induce vomiting or rinse the stomach, give activated charcoal , maintain vital body functions, and provide symptomatic treatment to the patient. Fluvoxamine-based drugs do not have a specific antidote . Due to the large volume of distribution of the substance, forced diuresis or dialysis .

Interaction

Fluvoxamine in combination with Tolbutamide leads to a decrease in the clearance of Tolbutamide , since the antidepressant inhibits the CYP2C9 isoenzyme .

of extrapyramidal disorders of the central nervous system with the combined use of this drug and Metoclopramide is described .

When Fluvoxamine is combined with Carbamazepine , the metabolism of the latter in the liver tissue is inhibited, since Fluvoxamine suppresses the activity of the CYP2D6 isoenzyme.

This substance increases the side effects of galantamine .

The combined use of the drug and valproic acid leads to increased effectiveness of the acid.

Since this substance acts as a non-competitive inhibitor of the CYP1A2 isoenzyme , it increases plasma concentrations of amitriptyline, imipramine, trimipramine, clopyramide, maprotiline .

Combining the drug with MAO inhibitors can lead to the development of serotonin syndrome .

The drug increases plasma concentrations and enhances adverse reactions from Bromeprazole, Diazepam, Alprazolam .

When used in combination with Buspirone, the effectiveness of the latter drug decreases.

The medicine increases the plasma concentration of Warfarin and increases the risk of bleeding.

When the substance is combined with Haloperidol, the concentration of lithium in the blood plasma increases.

The drug significantly increases the concentration of Clozapine in the blood plasma and enhances the toxic effects.

You should combine an antidepressant with caffeine , as side effects from taking psychostimulants may increase.

The substance increases the concentration of Olanzapine and Propranolol in the blood plasma.

The drug leads to increased toxicity of Theophylline , as it inhibits the enzyme CYP1A2 .

This substance can increase adverse reactions from taking Phenytoin .

When taken simultaneously, metabolic reactions and clearance of Quinidine .

Fluvoxamine

Suicide/suicidal ideation or clinical deterioration

Depression is associated with an increased risk of suicidal ideation, self-harm, and suicide attempts (suicidal behavior). 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.

Other psychiatric disorders for which fluvoxamine is prescribed may also be associated with an increased risk of suicidal behavior. 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 a significant degree of suicidal ideation before treatment are known to be at greater risk of suicidal ideation or suicide attempts 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 lack of clinical experience, fluvoxamine should not be used to treat depression in children. 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.

In addition, long-term safety data for children and adolescents regarding growth, maturation, cognitive and behavioral development are lacking.

Adults (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.

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 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 hepatic or renal 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 liver enzyme activity, most often accompanied by corresponding clinical symptoms, and in such cases the drug 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 the drug should be discontinued if epileptic seizures occur or their frequency increases.

Rare cases of the development of serotonin 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 antipsychotic drugs. Since 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 leading to 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, in rare cases hyponatremia may occur, which is reversible after discontinuation of fluvoxamine. Some cases have been caused by syndrome of inappropriate antidiuretic hormone secretion. 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 the drug is nausea, sometimes accompanied by vomiting. This side effect usually disappears within the first two weeks of treatment.

Visual impairment

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

Hematological disorders

There are reports of intracutaneous hemorrhages such as ecchymosis and purpura, as well as other hemorrhagic manifestations (for example, gastrointestinal bleeding or gynecological 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 or coagulation disorders).

Cardiac disorders

An increase in the risk of prolongation of the QT interval on the ECG and the risk of paroxysmal ventricular tachycardia of the “pirouette” type was noted 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).

Electroconvulsive therapy (ECT)

There is limited clinical experience with the use of fluvoxamine in conjunction with ECT, so such therapy should be carried out with caution.

Withdrawal syndrome

When you stop taking fluvoxamine, withdrawal syndrome may develop, although available data from preclinical and clinical studies have not revealed the occurrence of dependence on fluvoxamine treatment. The most common symptoms noted in case of drug withdrawal: dizziness, sensory disturbances (including paresthesia, visual disturbance and sensation of electric shock), sleep disturbances (including insomnia and vivid dreams), agitation, irritability, confusion, emotional lability, headache, nausea and/or vomiting, diarrhea, sweating, palpitations, tremors and anxiety (see section "Side effects"). Most of these symptoms are mild or moderate and self-limiting, but in some patients they can be severe and/or prolonged. These symptoms usually occur within the first few days after stopping treatment. 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 and Administration").

Mania/hypomania

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

special instructions

There are reports of the occurrence of purpura and ecchymosis when using this group of drugs. Therefore, in parallel, it is not recommended to prescribe atypical antipsychotics , tricyclic antidepressants , phenothiazines , non-steroidal anti-inflammatory drugs , aspirin . Also, caution should be observed during treatment in patients with a history of bleeding.

It should be remembered that during treatment and until remission is achieved, the patient remains at risk of attempting suicide.

In case of renal and liver failure, treatment is carried out under the supervision of a physician and begins with minimally active dosages.

Therapy with MAO inhibitors must be stopped 14 days before starting treatment with the drug.

Side effects and other risks

◊ Mechanism of side effects

Side effects are caused by an increase in serotonin. Most side effects occur immediately after starting treatment and go away over time, while the therapeutic effects increase over time.

◊ Side effects

• Gastroenterological (reduced appetite, nausea, diarrhea, constipation)
• Insomnia, sedation, agitation, tremor
• Sweating
• Dangerous side effects: seizures, mania, suicidal ideation
• Weight gain: very rare
• Sedation: very common
• Sexual dysfunction: yes

◊ What to do about side effects

1. Wait
2. For severe sedation, take at night
3. For anxious patients at the beginning of treatment - benzodiazepines
4. Reduce dose
5. Change drug
6. Side effects may appear briefly as the dose is increased

◊ Long-term use

Safely

◊Addiction

No.

◊ Overdose

• Very rare cases of fatal overdoses.
• In combination with other psychoactive substances - sedation, vomiting, diarrhea, convulsions, coma

Drugs containing (Fluvoxamine analogues)

Level 4 ATC code matches:
Actaparoxetine

Plizil

Fluxen

Paroxin

Surlift

Asentra

Elycea

Fluoxetine

Lenuksin

Escitalopram

Adepress

Selectra

Stimuloton

Citalopram

Cipramil

Zoloft

Paroxetine

Prozac

Paxil

Rexetine

Synonyms of Fluvoxamine (its trade names): Faverin, Luvox, Fevarin, Avoxin, Favoxil .

Reviews of Fluvoxamine

Reviews about the medicine are mixed. Many patients stop taking the pills after 2 days of therapy due to severe side effects. Most often this is nausea, anxiety, increased blood pressure and fear of death. Those who tolerate the drug well speak well of it. They write that after the first week of taking it, there is a noticeable relief in the condition, side effects practically disappear, and after completing the course, depression and OCD do not return.