indication

For management of depression and for Obsessive Compulsive Disorder (OCD). Has also been used in the management of bulimia nervosa.

pharmacology

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other 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 (5HT_1A, 5HT_1B, 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 exact mechanism of action of fluvoxamine has not been fully determined, but appears 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 5HT_1A autoreceptors. In-vitro studies suggest that fluvoxamine is more potent than clomipramine, fluoxetine, and desipramine as a serotonin-reuptake inhibitor. Studies have also demonstrated that fluvoxamine has virtually no affinity for α₁- or α₂-adrenergic, β-adrenergic, muscarinic, dopamine D₂, histamine H₁, GABA-benzodiazepine, opiate, 5-HT₁, or 5-HT₂ receptors.

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.

biotransformation

Hepatic

absorption

Well absorbed, bioavailability of fluvoxamine maleate is 53%.

half life

15.6 hours

route of elimination

The main human metabolite was fluvoxamine acid which, together with its N-acetylated analog, accounted for about 60% of the urinary excretion products. Approximately 2% of fluvoxamine was excreted in urine unchanged. Following a 14C-labelled oral dose of fluvoxamine maleate (5 mg), an average of 94% of drug-related products was recovered in the urine within 71 hours.

drug interactions

Acenocoumarol: Fluvoxamine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.

Almotriptan: Increased risk of CNS adverse effects

Aminophylline: Fluvoxamine may increase the effect and toxicity of aminophylline.

Amitriptyline: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluvoxamine is initiated, discontinued or dose changed.

Amoxapine: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amoxapine if fluvoxamine is initiated, discontinued or dose changed.

Amphetamine: Risk of serotoninergic syndrome

Anisindione: Fluvoxamine may increase the anticoagulant effect of anisindione by increasing its serum concentration.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Benzphetamine: Amphetamines may enhance the adverse/toxic effect of Serotonin Modulators. The risk of serotonin syndrome may be increased. Monitor patients closely for signs and symptoms of serotonin syndrome (e.g., agitation, tremor, tachycardia, etc.) when using amphetamines and serotonin modulators in combination.

Carbamazepine: Fluvoxamine increases the effect of carbamazepine

Carisoprodol: Strong CYP2C19 inhibitors such as fluvoxamine may decrease the metabolism of CYP2C19 substrates such as carisoprodol. Consider an alternative for one of the interacting drugs in order to avoid toxicity of the substrate. Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for increased effects of the CYP substrate if a CYP inhibitor is initiated/dose increased, and decreased effects if a CYP inhibitor is discontinued/dose decreased.

Cilostazol: Fluvoxamine increases the effect of cilostazol

Clomipramine: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluvoxamine is initiated, discontinued or dose changed.

Clozapine: The antidepressant increases the effect of clozapine

Desipramine: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of desipramine if fluvoxamine is initiated, discontinued or dose changed.

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dexfenfluramine: Risk of serotoninergic syndrome

Dextroamphetamine: Risk of serotoninergic syndrome

Dicumarol: Fluvoxamine may increase the anticoagulant effect of dicumarol by increasing its serum concentration.

Diethylpropion: Risk of serotoninergic syndrome

Dihydroergotamine: Possible ergotism and severe ischemia with this combination

Doxepin: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of doxepin if fluvoxamine is initiated, discontinued or dose changed.

Duloxetine: Fluvoxamine increases the effect and toxicity of duloxetine

Dyphylline: Increases the effect and toxicity of theophylline

Eletriptan: Increased risk of CNS adverse effects

Ergotamine: Possible ergotism and severe ischemia with this combination

Ethotoin: Increases the effect of hydantoin

Fenfluramine: Risk of serotoninergic syndrome

Fosphenytoin: Fluvoxamine may increase the therapeutic and adverse effects of fosphenytoin.

Frovatriptan: Increased risk of CNS adverse effects

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Imipramine: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of imipramine if fluvoxamine is initiated, discontinued or dose changed.

Isocarboxazid: Possible severe adverse reaction with this combination

Ketoprofen: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Linezolid: Combination associated with possible serotoninergic syndrome

Lithium: The SSRI, fluvoxamine, increases serum levels of lithium.

Mazindol: Risk of serotoninergic syndrome

Mephenytoin: Increases the effect of hydantoin

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methadone: Fluvoxamine increases the effect and toxicity of methadone

Methamphetamine: Risk of serotoninergic syndrome

Mexiletine: Fluvoxamine may increase the therapeutic and adverse effects of mexiletine.

Mirtazapine: Fluvoxamine may increase the therapeutic and adverse effects of mirtazapine.

Moclobemide: Increased incidence of adverse effects with this association

Naratriptan: Increased risk of CNS adverse effects

Nortriptyline: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of nortriptyline if fluvoxamine is initiated, discontinued or dose changed.

Olanzapine: Fluvoxamine increases the effect and toxicity of olanzapine

Oxtriphylline: Fluvoxamine may increase the therapeutic and adverse effects of oxtriphylline.

Oxycodone: Increased risk of serotonin syndrome

Phendimetrazine: Risk of serotoninergic syndrome

Phenelzine: Possible severe adverse reaction with this combination

Phentermine: Risk of serotoninergic syndrome

Phenylpropanolamine: Risk of serotoninergic syndrome

Phenytoin: Fluvoxamine may increase the therapeutic effect of phenytoin.

Protriptyline: The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, protriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of protriptyline if fluvoxamine is initiated, discontinued or dose changed.

Ramelteon: Fluvoxamine may increase the serum level and toxicity of ramelteon.

Rasagiline: Possible severe adverse reaction with this combination

Rizatriptan: Increased risk of CNS adverse effects

Ropinirole: Increases the effect and toxicity of ropinirole

Ropivacaine: Increases the effect and toxicity of ropivacaine

Selegiline: Possible severe adverse reaction with this combination

Sibutramine: Risk of serotoninergic syndrome

St. John's Wort: St. John's Wort increases the effect and toxicity of the SSRI, fluvoxamine.

Sumatriptan: Increased risk of CNS adverse effects

Tacrine: Fluvoxamine, a strong CYP1A2 inhibitor, may decrease the metabolism and clearance of tacrine, a CYP1A2 substrate. Concomitant therapy should be avoided as it could lead to severe toxic effects such as hepatotoxicity. If concomitant therapy is used, monitor for altered efficacy and toxic effects, such as gastrointestinal and hepatic effects, of tacrine.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Fluvoxamine. Consider alternate therapy or monitor for therapeutic/adverse effects of Fluvoxamine if Terbinafine is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Theophylline: Fluvoxamine may increase the therapeutic and adverse effects of theophylline.

Thiabendazole: The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Fluvoxamine by decreasing Fluvoxamine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Fluvoxamine if Thiabendazole is initiated, discontinued or dose changed.

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: The strong CYP1A2 inhibitor, Fluvoxamine, may decrease the metabolism and clearance of Thiothixene, a CYP1A2 substrate. Consider alternate therapy or monitor for changes in Thiothixene therapeutic and adverse effects if Fluvoxamine is initiated, discontinued or dose changed.

Tiaprofenic acid: Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.

Tizanidine: Fluvoxamine inhibits the metabolism and clearance of tizanidine. Concomitant therapy is contraindicated.

Tolmetin: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Tramadol: Tramadol may increase the risk of serotonin syndrome and seizures.

Tranylcypromine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Treprostinil: The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Fluvoxamine. Monitor for increased bleeding during concomitant thearpy.

Trimipramine: The strong CYP2C19 inhibitor, fluvoxamine, may decrease the metabolism and clearance of trimipramine, a CYP2C19 substrate. Additive modulation of serotonin activity may also increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome and changes in therapeutic and adverse effects of trimipramine if fluvoxamine is initiated, discontinued or dose changed.

Triprolidine: The CNS depressants, Triprolidine and Fluvoxamine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Warfarin: Fluvoxamine may increase the anticoagulant effect of warfarin by increasing its serum concentration.

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and fluvoxamine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.