Fluvoxamine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Included in the formulation

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АТХ:

N.06.A.B.08 Fluvoxamine

Pharmacodynamics:Selectively inhibits the reverse neuronal capture of serotonin from the synaptic cleft, blocking the membrane pump of the presynaptic membrane. Promotes the enhancement of serotonergictransmission and reduction of serotonin turnover. Blocking the reuptake of serotonin in platelets. Slightly affects the re-uptake of dopamine and norepinephrine. Does not affect histaminergicye, alpha and beta adrenergichem-cholinergice, dopaminergice, 5-HT1- and 5-HT2-receptors. There are data on the effectiveness of fluvoxamine in the obsessive-comp.including children and adolescents (8-17 years).

Pharmacokinetics:

Well absorbed from the digestive tract. Bioavailability is not dependent on food intake and is about 53% (due to the effect of the first passage through the liver). When administered for 10 days at doses of 100, 200 and 300 mg per day, the equilibrium concentration in the blood is reached after about 1 week. The maximum concentration in the equilibrium state is reached within 3-8 hours after administration and is 88, 283 and 546 ng / ml, respectively. Correlation between plasma concentration and efficacy was not observed.Binding to plasma proteins - about 80% (mainly with albumin). The distribution volume is high - 25 l / kg. In the liver, it undergoes demethylation and deamination; identified nine inactive metabolites (fluvoxamine acid, fluvoxethanol, etc.). Inhibits cytochrome P450 isoenzymes: CYP1A2, CYP3A4, CYP2C9, weaker effects on CYP2D6. The half-life is 15-20 hours. 94% is excreted in the urine for 71 hours (2-3% unchanged).

When studying the excretion of fluvoxamine in patients with impaired renal function (creatinine clearance of 5-45 ml / min), who received it 50 mg twice a day, no cumulation was observed; with hepatic dysfunction, the excretion of fluvoxamine decreased by 30%. In patients with a genetically determined deficiency of the CYP2D6 enzyme (2-10% of the population), the maximum concentration, systemic exposure and half-life increase by 52%, 200% and 62%, respectively. In elderly patients (66-73 years) maximum concentration fluvoxamine is 40% higher, excretion is 50% lower compared to younger patients (19-35 years). The half-life in the elderly is 17.4 and 25.9 hours after admission in a dose of 50 and 100 mg, respectively (in young people - 13.6 and 15.6 hours).In smokers, the bioavailability of fluvoxamine is reduced by induction of its metabolism (by 25%).

Indications:Depression of a different genesis, obsessive-comp.an upset disorder.

ICD-10

V.F30-F39.F31 Bipolar affective disorder

V.F30-F39.F32 Depressive episode

V.F30-F39.F33 Recurrent depressive disorder

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F40-F48.F42 Obsessive-compulsive disorder

Contraindications:Hypersensitivityliver failure, simultaneous administration of astemizole, cisapride, terfenadine, agents that inhibit MAO (including furazolidone, procarbazine, selegiline) - treatment with fluvoxamine can be started 2 weeks after stopping the intake of an irreversible MAO inhibitor and the day after stopping the taking of reversible MAO inhibitor, breastfeeding, children under 8 years old.

Carefully:Epilepsy, pregnancy; drug dependence, mania, hypomania, convulsions or myocardial infarction in history, renalI insufficiency, elderly age, patients with a tendency to bleeding (thrombocytopenia).

Pregnancy and lactation:

Use with caution in pregnancy, comparing the intended benefit to the mother and the potential risk to the fetus.

Action category for the fetus by FDA - C.

For the duration of treatment, breastfeeding should be abandoned.

Dosing and Administration:

It is installed individually. At the beginning of treatment, the daily dose is 50-100 mg (it is recommended to take at night). With insufficient effectiveness, the daily dose can be increased to 150-200 mg. The maximum daily dose is 300 mg. If the daily dose is more than 100 mg, then it should be divided into 2-3 doses.

According to official WHO recommendations, treatment with antidepressants should be continued for at least 6 months after the recovery of the depressive episode.

Side effects:

From the side digestive system: often - nausea, sometimes accompanied by vomiting (usually disappears in the first 2 weeks of treatment); possibly - constipation, anorexia, dyspepsia, diarrhea, discomfort in the epigastric region, dry mouth, discomfort; rarely - increased activity of liver enzymes, mainly in patients of senile age - transient hyponatremia (in some cases due to the syndrome of inadequate secretion of ADH, disappears after the withdrawal of fluvoxamine).

From the side CNS: possible drowsiness, dizziness, headache, irritability, insomnia, anxiety, hypomanic and manic conditions, psychomotor agitation, a sense of fear, tremor, a feeling of discomfort, asthenia; After a sharp withdrawal of fluvoxamine, headache, nausea, dizziness, and a sense of fear were observed in rare cases.

From the side of cardio-vascular system: possibly a slight decrease in heart rate (by 2-6 beats per minute), palpitations, tachycardia, postural hypotension.

Other: possibly increased sweating, change in body weight, impaired vision, tremor. arthralgia, myalgia; cough, sinusitis, bronchitis; allergic reactions.

Some of the above side effects may be symptoms of depression and are not due to the action of fluvoxamine.

Overdose:

Symptoms: dizziness, drowsiness, dry mouth, nausea, vomiting, diarrhea, brady- or tachycardia, arterial hypotension, ECG changes, impaired hepatic function, mydriasis, tremor, myoclonus, seizures, oliguria, coma. Lethal outcomes are described.

Treatment: stimulation of vomiting or gastric lavage, reception of activated carbon, ECG monitoring, maintenance of vital functions, symptomatic therapy. There is no specific antidote. Dialysis and forced diuresis are ineffective (due to the large volume of distribution).

Interaction:

β-blockers (propranolol, metoprolol) - increasing their concentrations and the risk of side effects (cardiodepressive effect, orthostatic collapse).

Astemizole, cisapride and terfenadine inhibit their metabolism (CYP3A4), increase concentrations and risk of arrhythmia (torsades de pointes) with possible fatal outcome.

Benzodiazepines metabolized in the cytochrome P450 system (alprozalam, bromazepam, diazepam, midazolam, triazolam) - increase in their half-life and toxicity; fluvoxamine does not affect the metabolism of lorazepam, oxazepam and temazepam (glucuronidation).

MAO inhibitors - confusion, agitation, gastrointestinal disorders, hyperthermia, convulsions, hypertensive crises, serotonin syndrome, death. Simultaneous use is contraindicated, to withstand a 14-day interval after the course of MAO inhibitors.

Clozapine - increasing its concentration and toxicity.

Theophylline - increase in its concentrations and toxicity: arrhythmias, headache, fatigue, tremor, vomiting, convulsions.

Tricyclic antidepressants - a significant increase in their concentrations and toxicity.

Special instructions:

The interval between cancellation of MAO inhibitors and the onset of fluvoxamine intake or its cancellation and initiation of MAO inhibitors should be at least 14 days. It requires careful monitoring of patients with suicidal tendencies, especially at the beginning of treatment. To patients of advanced age fluvoxamine should be administered in a reduced dosage. With caution apply to drivers of vehicles and people whose activities require increased concentration and speed of psychomotor reactions. During treatment should avoid drinking alcohol.

Caution should be given to patients who have a history of drug dependence or abuse.

Impact on the ability to drive vehicles and manage mechanisms.

Patients receiving fluvoxamine, caution should be exercised when engaging in potentially hazardous activities,require increased attention and rapid psychomotor reactions.

Instructions

Fluvoxamine (Fluvoxaminum)