QuickView for Fluoxetine (compound)

Summary
General Info

PubChem

PubChem Compound 11758740

Name:	Fluoxetine
PubChem Compound ID:	11758740
Description:	The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.
Molecular formula:	C₁₇H₁₈F₃NO
Molecular weight:	311.334 g/mol

DrugBank

Identification

Name:	Fluoxetine
Name (isomeric):	DB00472
Drug Type:	small molecule
Description:	The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.
Synonyms:	Fluoxetine Hcl; Fluoxetine Hydrochloride; Fluoxetina [Spanish]; Fluoxetinum [INN-Latin]; Fluoxetina [INN-Spanish]
Brand:	Adofen, Animex-On, Foxetin, Portal, Fluval, Fontex, Reneuron, Prozac Weekly, Fluctin, Eufor, Sarafem, Pulvules, Prozac, Fluoxeren, Deprex
Category:	Antidepressants, Second-Generation, Antidepressive Agents, Second-Generation, Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Uptake Inhibitors
CAS number:	54910-89-3

Pharmacology

Indication:	Labeled indication include: major depressive disorder (MDD), moderate to severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder with or without agoraphobia, and combination treatment with olanzapine for treatment-resistant or bipolar I depression. Unlabeled indications include: selective mutism, mild dementia-associated agitation in nonpsychotic patients, post-traumatic stress disorder (PTSD), social anxiety disorder, chronic neuropathic pain, fibromyalgia, and Raynaud's phenomenon.
Pharmacology:	Fluoxetine, an antidepressant agent belonging to the selective serotonin reuptake inhibitors (SSRIs), is used to treat depression, bulimia nervosa, premenstrual dysphoric disorder, panic disorder and post-traumatic stress. According to the amines hypothesis, a functional decrease in the activity of amines, such as serotonin and norepinephrine, woul... show more » Fluoxetine, an antidepressant agent belonging to the selective serotonin reuptake inhibitors (SSRIs), is used to treat depression, bulimia nervosa, premenstrual dysphoric disorder, panic disorder and post-traumatic stress. According to the amines hypothesis, a functional decrease in the activity of amines, such as serotonin and norepinephrine, would result in depression; a functional increase of the activity of these amines would result in mood elevation. Fluoxetine's effects are thought to be associated with the inhibition of 5HT receptor, which leads to an increase of serotonin level. show less «
Mechanism of Action:	Metabolized to norfluoxetine, fluoxetine is a selective serotonin-reuptake inhibitor (SSRI), it blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT_1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine re... show more » Metabolized to norfluoxetine, fluoxetine is a selective serotonin-reuptake inhibitor (SSRI), it blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT_1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. show less «
Absorption:	Well absorbed from the GI tract following oral administration. Oral bioavailability is estimated to be at least 60-80%. Peak plasma concentrations occur within 4-8 hours following oral administration of conventional dosage preparations.
Protein binding:	94.5%
Biotransformation:	Limited data from animal studies suggest that fluoxetine may undergo first-pass metabolism may occur via the liver and/or lungs. Fluoxetine appears to be extensively metabolized, likely in the liver, to norfluoxetine and other metabolites. Norfluoxetine, the principal active metabolite, is formed via N-demethylation of fluoxetine. Norfluoxetine appears to be comparable pharmacologic potency as fluoxetine. Fluoxetine and norfluoxetine both undergo phase II glucuronidation reactions in the liver. It is also thought that fluoxetine and norfluoxetine undergo O-dealkylation to form p-trifluoromethylphenol, which is then subsequently metabolized to hippuric acid.
Route of elimination:	The primary route of elimination appears to be hepatic metabolism to inactive metabolites excreted by the kidney.
Half Life:	1-3 days
Toxicity:	Symptoms of overdose include agitation, restlessness, hypomania, and other signs of CNS excitation. LD₅₀=284mg/kg (orally in mice). The most frequent side effects include: nervous system effects such as anxiety, nervousness, insomnia, drowsiness, fatigue or asthenia, tremor, and dizziness or lightheadedness; GI effects such as anorexia, nausea, and diarrhea; vasodilation; dry mouth; abnormal vision; decreased libido; abnormal ejaculation; rash; and sweating. Withdrawal symptoms include flu-like symptoms, insomnia, nausea, imbalance, sensory changes and hyperactivity.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol.

Take with food to reduce irritation and nausea.

Drug interaction:

Tamoxifen	Fluoxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
Phenelzine	Possible severe adverse reaction with this combination
Amoxapine	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Almotriptan	Increased risk of CNS adverse effects
Triprolidine	The CNS depressants, Triprolidine and Fluoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Tamoxifen	Fluoxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
Phenelzine	Possible severe adverse reaction with this combination
Amoxapine	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Almotriptan	Increased risk of CNS adverse effects
Triprolidine	The CNS depressants, Triprolidine and Fluoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Dextromethorphan	Combination associated with possible serotoninergic syndrome
Anisindione	The SSRI, fluoxetine, increases the effect of anticoagulant, anisindione.
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.
Phentermine	Risk of serotoninergic syndrome
Phenytoin	Fluoxetine increases the effect of phenytoin
Dicumarol	The SSRI, fluoxetine, increases the effect of anticoagulant, dicumarol.
Isocarboxazid	Possible severe adverse reaction with this combination
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Fenfluramine	Risk of serotoninergic syndrome
Troleandomycin	Possible serotoninergic syndrome with this combination
Terbinafine	Terbinafine may reduce the metabolism and clearance of Fluoxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Fluoxetine if Terbinafine is initiated, discontinued or dose changed.
Dihydroergotamine	Possible ergotism and severe ischemia with this combination
Dextroamphetamine	Risk of serotoninergic syndrome
Tiaprofenic acid	Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
Carvedilol	The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
Rasagiline	Possible severe adverse reaction with this combination
Propafenone	Additive QTc-prolongation may occur increasing the risk of serious life-threatening arrhythmias. Fluoxetine may also increase the serum concentration of propafenone. Use caution during concomitant therapy and monitor for QTc-prolongation.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Naratriptan	Increased risk of CNS adverse effects
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and fluoxetine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Fluoxetine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if fluoxetine is initiated, discontinued or dose changed.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Ritonavir	Increased risk of serotonin syndrome
Atomoxetine	The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Protriptyline	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Tipranavir	Tipranavir increases the concentration of Fluoxetine. The Fluoxetine dose may require an adjustment.
Cyproheptadine	Possible antagonism of action
Imipramine	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Clarithromycin	Possible serotoninergic syndrome with this combination
Astemizole	Increased risk of cardiotoxicity and arrhythmias
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Eletriptan	Increased risk of CNS adverse effects
Tolbutamide	Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Fluoxetine. Consider alternate therapy or monitor for changes in Fluoxetine therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Tramadol	The use of two serotonin modulators, such as fluoxetine and tramadol, may increase the risk of serotonin syndrome. Fluoxetine may decrease the effect of tramadol by decreasing active metabolite production.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Clomipramine	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Rizatriptan	Increased risk of CNS adverse effects
Ginkgo biloba	Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Dexfenfluramine	Risk of serotoninergic syndrome
Clozapine	The antidepressant increases the effect of clozapine
Cyclosporine	The antidepressant increases the effect and toxicity of cyclosporine
Lithium	The SSRI, fluoxetine, increases serum levels of lithium.
Methamphetamine	Risk of serotoninergic syndrome
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Fosphenytoin	Fluoxetine increases the effect of phenytoin
Mazindol	Risk of serotoninergic syndrome
Amitriptyline	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Cilostazol	Fluoxetine, a moderate CYP2C19 inhibitor, may decrease the metabolism of cilostazol. Monitor for changes in the therapeutic and adverse effects of cilostazol if fluoxetine is initiated, discontinued or dose changed.
Warfarin	The SSRI, fluoxetine, increases the effect of anticoagulant, warfarin.
Selegiline	Possible severe adverse reaction with this combination
St. John's Wort	St. John's Wort increases the effect and toxicity of the SSRI, fluoxetine.
Ethotoin	Fluoxetine increases the effect of phenytoin
Tizanidine	Fluoxetine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Nortriptyline	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Diethylpropion	Risk of serotoninergic syndrome
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Moclobemide	Risk of serotoninergic syndrome
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.
Tacrine	The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Fluoxetine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Fluoxetine is initiated, discontinued or if the dose is changed.
Amphetamine	Risk of serotoninergic syndrome
Phenylpropanolamine	Risk of serotoninergic syndrome
Tamsulosin	Fluoxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Fluoxetine is initiated, discontinued, or dose changed.
Carbamazepine	Carbamazepine may decrease the serum concentration of fluoxetine by increasing its metabolism. Fluoxetine may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses are changed.
Tolmetin	Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
Trimipramine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, trimipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used cautiously.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Risperidone	The SSRI, fluoxetine, increases the effect and toxicity of risperidone.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Oxycodone	Increased risk of serotonin syndrome
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Frovatriptan	Increased risk of CNS adverse effects
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Erythromycin	Possible serotoninergic syndrome with this combination
Doxepin	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Linezolid	Linezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.
Mephenytoin	Fluoxetine increases the effect of phenytoin
Sibutramine	Risk of serotoninergic syndrome
Desipramine	The SSRI, fluoxetine, 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 fluoxetine is initiated, discontinued or dose changed.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Propranolol	The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, propranolol.
Sumatriptan	Increased risk of CNS adverse effects
Tolterodine	Fluoxetine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
Metoprolol	The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, metoprolol.
Josamycin	Possible serotoninergic syndrome with this combination
Phendimetrazine	Risk of serotoninergic syndrome
Treprostinil	The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Fluoxetine. Monitor for increased bleeding during concomitant thearpy.
Acenocoumarol	The SSRI, fluoxetine, increases the effect of anticoagulant, acenocoumarol.
Ergotamine	Possible ergotism and severe ischemia 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.

show less «

Targets

Sodium-dependent serotonin transporter

5-hydroxytryptamine 2A receptor

Enzymes

Transporters

Multidrug resistance protein 1