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Active ingredient: Fluvoxamine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Antidepressants
  • Anti-anxiety Agents
  • Second-Generation
  • Selective Serotonin Reuptake Inhibitors (SSRIs)

Dosage Forms

  • Tablet

Brands / Synonyms

Dumirox; Faverin; Fevarin; Floxyfral; Fluvoxamina [Inn-Spanish]; Fluvoxamine; Fluvoxamine maleate; Fluvoxaminum [Inn-Latin]; Luvox; Luvox CR; Maveral

Indications

For treatment of depression and for Obsessive Compulsive Disorder (OCD)

Pharmacology

Fluvoxamine is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Fluvoxamine does not inhibit monoamine oxidase.

Mechanism of Action

The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Fluvoxamine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.

Absorption

Well absorbed, bioavailability of fluvoxamine maleate is 53%.

Toxicity

Side effects include anorexia, constipation, dry mouth, headache, nausea, nervousness, skin rash, sleep problems, somnolence, liver toxicity, mania, increase urination, seizures, sweating increase, tremors, or Tourette's syndrome.

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

No information provided.

Drug Interactions

Potential for Interaction with Monoamine Oxidase Inhibitors

In patients receiving another serotonin reuptake inhibitor drug in combination with monoamine oxidase inhibitors (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have discontinued that drug and have been started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, it is recommended that Fluvoxamine Tablets not be used in combination with MAOIs, or within 14 days of discontinuing treatment with a MAOI. After stopping Fluvoxamine Tablets, at least 2 weeks should be allowed before starting a MAOI.

Potential Terfenadine, Astemizole, and Cisapride Interactions

Terfenadine, astemizole and cisapride are all metabolized by the cytochrome P450IIIA4 isozyme, and it has been demonstrated that ketoconazole, a potent inhibitor of IIIA4, blocks the metabolism of these drugs, resulting in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, and cisapride cause QT prolongation and have been associated with torsades de pointes-type ventricular tachycardia, sometimes fatal. As noted below, a sub- for fluvoxamine in combination with alprazolam, a drug that is known to be metabolized by the IIIA4 isozyme. Although it has not been definitively demonstrated that fluvoxamine is a potent IIIA4 inhibitor, it is likely to be, given the substantial interaction of fluvoxamine with alprazolam. Consequently, it is recommended that fluvoxamine not be used in combination with either terbinafine, astemizole, or cisapride.

Other Potentially Important Drug Interactions:

Benzodiazepines: Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam elc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. The clearance of benzodiazepines metabolized by glucuronidation (e. g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine.

Alprazolam: When fluvoxamine maleate (100 mg qd) and alprazolam (1 mg q.d. were co-administered to steady state, plasma concentration and other pharmacokinetics parameters (AUC, Cmax, T1/2,) of alprazolam were approximately twice those observed when alprazolam was administered alone; oral clearance was reduced by about 50%. The elevated plasma alprazolam concentrations resulted in decreased psychomotor performance and memory. This interaction, which has not been investigated using higher doses of fluvoxamine, may be more pronounced if a 300 mg daily dose is co-administered, particularly since fluvoxamine exhibits non-linear pharmacokinetics over the dosage range 100-300 mg. If alprazolam is co-administered with Fluvoxamine Tablets, the initial alprazolam dosage should be at least halved and titration to the lowest effective dose is recommended. No dosage adjustment is required for Fluvoxamine Tablets.

Diazepam: The co-administration of Fluvoxamine Tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic co-administration.

Evidence supporting the conclusion that it is inadvisable to co-administer fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (R= B), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study.

It is likely that experience significantly underestimates the degree of accumulation that might occur with repealed diazepam administration. Moreover, as noted with alprazolam, the effect of fluvoxamine may even be more pronounced when it is administered at higher doses. Accordingly, diazepam and fluvoxamine should not ordinarily be co-administered.

Theophylline: The effect of steady-state fluvoxamine l50 mg bid on the pharmacokinetics of a single dose of Theophylline (375 mg) as 442 mg aminophylline was evaluated in 12 healthy non-smoking, male volunteers. The clearance of theophylline was decreased approximately 3-fold. Therefore, if theophylline is co-administered with fluvoxamine maleate, its dose should be reduced to one third of the usual daily maintenance dose and plasma concentrations of theophylline should to monitored. No dosage adjustment is required for Fluvoxamine Tablets.

Warfarin: When fluvoxamine maleate (50 mg tid) was administered concomitantly with warfarin for two weeks, warfarin plasma concentrations increased by 98% and prothrombin times were prolonged. Thus patients receiving oral anticoagulants and Fluvoxamine Tablets should have their prothrombin time monitored and their anticoagulant dose adjusted accordingly. No dosage adjustment is required for Fluvoxamine Tablets.

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