Luvox

The drug selectively inhibits reverse neuronal uptake of serotonin from synaptic gap by blocking the membrane pump of the presynaptic membrane. It enhances serotonergic transmission and decreases serotonin turnover. The drug blocks the reuptake of serotonin in platelets. It has a little effect on the reuptake of dopamine and norepinephrine.


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Description

Luvox pharmacological action is antidepressant.

The drug selectively inhibits reverse neuronal uptake of serotonin from synaptic gap by blocking the membrane pump of the presynaptic membrane. It enhances serotonergic transmission and decreases serotonin turnover. The drug blocks the reuptake of serotonin in platelets. It has a little effect on the reuptake of dopamine and norepinephrine. The drug does not affect histaminergic, alpha – and beta-adrenergic, m-cholinergic, dopaminergic, 5-HT1 and 5-HT2 receptors. There is evidence of the effectiveness of Luvox in obsessive-compulsive disorders, including children and adolescents (8-17 years).
It is well absorbed from the gastrointestinal tract. Bioavailability does not depend on food intake and is about 53% (due to the effect of “first passage” through the liver). When the drug is taken for 10 days at doses of 100, 200 and 300 mg/day, the equilibrium concentration in the blood is achieved in 1 week. Cmax at steady state is achieved within 3-8 h after ingestion and is 88, 283 and 546 ng/ml, respectively. Correlation between plasma concentration and efficacy is not marked. The binding with plasma proteins is about 80% (mainly to albumin). The volume of distribution is high — 25 l/kg. It undergoes demethylation and deamination in the liver; there were identified nine inactive metabolites (fluvoxamine acid, fluvoxethanol, etc.). It inhibits the isoenzymes of cytochrome P450: CYP1A2, CYP3A4, CYP2C9, and has less effect on CYP2D6. T1/2 — 15-20 h. the 94% is excreted in the urine within 71 hours (2-3% in an unmodified form).

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During the study of excretion of fluvoxamine in patients with impaired renal function (Cl creatinine 5-45 ml/min) receiving it at the dosage of 50 mg twice a day, the cumulation was not observed; in case of hepatic dysfunction the excretion of Luvox was reduced by 30%. Patients with genetically determined deficiency of the enzyme CYP2D6 (2-10% of the population) Cmax, AUC and T1/2 noticed the increase of it by 52%, 200% and 62%, respectively. Elderly patients (66-73 years) observed the Cmax of Luvox to 40% higher and excretion — 50% lower compared to younger patients (19-35 years). T1/2 of elderly people is 17.4 and 25.9 per h after administration at a dose of 50 and 100 mg respectively (young — 13.6 and 15.6 hours). Smokers noticed the decreased bioavailability of fluvoxamine by induction of its metabolism (25%).

The studies on animals have shown a decrease in body weight and survival of the fruit, the increase of the frequency of their intrapartum death when taking Luvox during pregnancy at a dose 2-4 times higher than MRDC. The concentration in breast milk is 3 times lesser than that in blood plasma (0.09 and 0.31 mg/l, respectively when taken a dose of 100 mg/day).

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Indications for use

Depression of different Genesis, obsessive-compulsive disorder

Drug Contradictions

Epilepsy, pregnancy; drug dependence, mania, hypomania, seizure or myocardial infarction in anamnesis.

Reception during pregnancy and breastfeeding

It should be used with caution during pregnancy, comparing the expected benefit to the mother and the potential risk to the fetus.

The category of the effect on the fetus by FDA — C.

At the time of treatment you should abandon breastfeeding.

Side effects

22% from 1087 patients with obsessive-compulsive disorders and depression stooped taking Luvox in connection with the development of side effects. They included (in brackets we noted the % of occurrence in the placebo group):

From the nervous system and sensory organs: headache 3% (1%), dizziness 2% (less than 1%), asthenia 2% (less than 1%) insomnia 4% (1%), drowsiness 4% (less than 1%), nervousness 2% (less than 1%), anxiety 1% (less than 1%), agitation of 2% (less than 1%).

Gastrointestinal system: nausea 9% (1%), anorexia 1% (less than 1%), dry mouth 1% (less than 1%) dyspepsia 1% (less than 1%), vomiting 2% (less than 1%), diarrhea 1% (less than 1%), abdominal pain 1% (0%).

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Drug interaction

It is incompatible with the means, inhibiting MAO, including furazolidone, procarbazine and selegiline (risk of serotonergic syndrome and death). The development of serotonergic syndrome (chills, hyperthermia, muscle rigidity, myoclonus, autonomic lability, hypertensive crisis, excitation, tremor, restlessness, cramps, diarrhea, hypomanic state) is possible in patients receiving drugs with serotonergic activity (tryptophan, lithium compounds). It increases concentration of propranolol in plasma (5 times), metoprolol and other beta-blockers, anticoagulants, including warfarin (98%), carbamazepine, clozapine (3 times), tricyclic antidepressants (amitriptillin, clomipramine, imipramine). Reception of Luvox concurrently with the anti-psychotic group of butyrophenone, including haloperidol, leads to an increase of their plasma concentrations, or to a 2-10-times increase in the content of Luvox. It can inhibit the biotransformation of drugs, which are metabolized with the participation of isoenzymes CYP1A2, CYP3A4, CYP2C9, CYP2D6 cytochrome P450 (phenytoin, quinidine, theophylline, caffeine, etc.), increasing the risk of adverse reactions. The intake of Luvox in the background of astemizole, cisapride, or terfenadine may lead to a marked lengthening of the QT interval and the occurrence of arrhythmias of “pirouette” type (may be fatal).

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