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Identification
Name Fluoxetine
Accession Number DB00472 (APRD00530)
Type small molecule
Groups approved
Description

Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Flouxetine may be used to treat major depressive disorder (MDD), moderate to severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder with or without agoraphobia, and in combination with olanzapine for treatment-resistant or bipolar I depression. Fluoxetine is the most anorexic and stimulating SSRI.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Fluoxetina [INN-Spanish]
Fluoxetina [Spanish]
Fluoxetine Hcl
Fluoxetine Hydrochloride
Fluoxetinum [INN-Latin]
Salts Not Available
Brand names
Name Company
Adofen
Animex-On
Eufor
Fluctin
Fluoxeren
Fluval
Fontex
Foxetin
Portal
Prozac Dista
Prozac Weekly
Pulvules
Reneuron
Sarafem Lilly, Warner, Chilcott
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Brand mixtures Not Available
Categories
  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Antidepressants, Second-Generation
  • Serotonin Uptake Inhibitors
  • Antidepressive Agents, Second-Generation
CAS number 54910-89-3
Weight Average: 309.3261
Monoisotopic: 309.134048818
Chemical Formula C17H18F3NO
InChI Key InChIKey=RTHCYVBBDHJXIQ-UHFFFAOYSA-N
InChI
InChI=1S/C17H18F3NO/c1-21-12-11-16(13-5-3-2-4-6-13)22-15-9-7-14(8-10-15)17(18,19)20/h2-10,16,21H,11-12H2,1H3
Plain Text
IUPAC Name
methyl({3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl})amine
SMILES
CNCCC(OC1=CC=C(C=C1)C(F)(F)F)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropylamines
Substructures
  • Benzyl Alcohols and Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Halogen Derivatives
  • Benzene and Derivatives
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • Phenyl Esters
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.
Pharmacodynamics 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.
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 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
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.
Volume of distribution
  • 20-45 L/kg
Protein binding 94.5%
Metabolism 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
Clearance Not Available
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
Pathways
Pathway Name SMPDB ID
Smp00426 Fluoxetine Pathway SMP00426
Pharmacoeconomics
Manufacturers
  • Barr laboratories inc
  • Dr reddys laboratories ltd
  • Eli lilly and co
  • Mutual pharmacal co
  • Watson laboratories inc
  • Alembic ltd
  • Alphapharm party ltd
  • Aurobindo pharma ltd
  • Beijing double crane pharmaceutical co ltd
  • Carlsbad technology inc
  • Dr reddys laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Landela pharmaceutical
  • Mallinckrodt inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Pliva inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Wockhardt ltd
  • Lilly research laboratories div eli lilly and co
  • Actavis mid atlantic llc
  • Aurobindo pharma usa inc
  • Hi tech pharmacal co inc
  • Lannett holdings inc
  • Novex pharma
  • Pharmaceutical assoc inc div beach products
  • Silarx pharmaceuticals inc
  • Wockhardt eu operations (swiss) ag
  • Warner chilcott inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral 10 mg
Capsule Oral 20 mg
Capsule Oral 40 mg
Capsule, delayed release Oral 90 mg
Solution Oral 20 mg/5 ml
Tablet Oral 10 mg
Tablet Oral 15 mg
Tablet Oral 20 mg
Prices
Unit description Cost Unit
PROzac 20 mg/5ml Solution 120ml Bottle 266.51 USD bottle
PROzac Weekly 1 Package = 4 capsule (90 mg) Disp Pack 140.77 USD disp
Sarafem 7 10 mg tablet Box 61.08 USD box
Sarafem 7 20 mg tablet Each Box Contains 7 tablet 59.55 USD box
Prozac weekly 90 mg capsule 34.5 USD capsule
PROzac 40 mg capsule 13.89 USD capsule
Fluoxetine hcl powder 8.32 USD g
Sarafem 10 mg tablet 7.91 USD tablet
Sarafem 15 mg tablet 7.91 USD tablet
Sarafem 20 mg tablet 7.91 USD tablet
PROzac 20 mg capsule 6.95 USD capsule
PROzac 10 mg capsule 6.77 USD capsule
FLUoxetine HCl 40 mg capsule 5.54 USD capsule
PROzac 10 mg tablet 4.31 USD tablet
Fluoxetine hcl 20 mg tablet 4.26 USD tablet
Rapiflux 20 mg tablet 3.11 USD tablet
FLUoxetine HCl 20 mg capsule 2.77 USD capsule
Fluoxetine hcl 10 mg tablet 2.72 USD tablet
FLUoxetine HCl 10 mg capsule 2.7 USD capsule
Fxt 40 40 mg Capsule 2.3 USD capsule
Prozac 10 mg Capsule 2.02 USD capsule
Prozac 20 mg Capsule 2.02 USD capsule
Apo-Fluoxetine 10 mg Capsule 1.13 USD capsule
Co Fluoxetine 10 mg Capsule 1.13 USD capsule
Mylan-Fluoxetine 10 mg Capsule 1.13 USD capsule
Novo-Fluoxetine 10 mg Capsule 1.13 USD capsule
Nu-Fluoxetine 10 mg Capsule 1.13 USD capsule
Phl-Fluoxetine 10 mg Capsule 1.13 USD capsule
Pms-Fluoxetine 10 mg Capsule 1.13 USD capsule
Ratio-Fluoxetine Hydrochloride 10 mg Capsule 1.13 USD capsule
Sandoz Fluoxetine 10 mg Capsule 1.13 USD capsule
Apo-Fluoxetine 20 mg Capsule 1.06 USD capsule
Co Fluoxetine 20 mg Capsule 1.06 USD capsule
Mylan-Fluoxetine 20 mg Capsule 1.06 USD capsule
Novo-Fluoxetine 20 mg Capsule 1.06 USD capsule
Nu-Fluoxetine 20 mg Capsule 1.06 USD capsule
Phl-Fluoxetine 20 mg Capsule 1.06 USD capsule
Pms-Fluoxetine 20 mg Capsule 1.06 USD capsule
Ratio-Fluoxetine Hydrochloride 20 mg Capsule 1.06 USD capsule
Sandoz Fluoxetine 20 mg Capsule 1.06 USD capsule
FLUoxetine HCl 20 mg/5ml Solution 1.03 USD ml
Apo-Fluoxetine 4 mg/ml Liquid 0.61 USD liquid
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6960577 1997-11-01 2017-11-01
United States 5910319 1997-05-29 2017-05-29
Properties
State solid
Experimental Properties
Property Value Source
melting point 179-182 °C Not Available
water solubility 50 mg/mL at 25 °C Not Available
logP 4.05 ADLARD,M ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.70e-03 g/l ALOGPS
logP 4.09 ALOGPS
logP 4.17 ChemAxon
logS -5.3 ALOGPS
pKa (strongest basic) 9.8 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 21.26 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 80.37 ChemAxon
polarizability 30.33 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Wong DT, Bymaster FP, Engleman EA: Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci. 1995;57(5):411-41. Pubmed
  2. Wong DT, Horng JS, Bymaster FP, Hauser KL, Molloy BB: A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. Life Sci. 1974 Aug 1;15(3):471-9. Pubmed
  3. Carlsson A, Wong DT: Correction: a note on the discovery of selective serotonin reuptake inhibitors. Life Sci. 1997;61(12):1203. Pubmed
  4. Gerber PE, Lynd LD: Selective serotonin-reuptake inhibitor-induced movement disorders. Ann Pharmacother. 1998 Jun;32(6):692-8. Pubmed
  5. Caley CF: Extrapyramidal reactions and the selective serotonin-reuptake inhibitors. Ann Pharmacother. 1997 Dec;31(12):1481-9. Pubmed
External Links
Resource Link
KEGG Drug D00823 Link_out
PubChem Compound 3386 Link_out
PubChem Substance 46507902 Link_out
ChemSpider 3269 Link_out
BindingDB 30130 Link_out
ChEBI 5118 Link_out
ChEMBL 5118 Link_out
Therapeutic Targets Database DAP000186 Link_out
PharmGKB PA449673 Link_out
IUPHAR 203 Link_out
Guide to Pharmacology 203 Link_out
Drug Product Database 2242124 Link_out
RxList http://www.rxlist.com/cgi/generic/fluoxetine.htm Link_out
Drugs.com http://www.drugs.com/fluoxetine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Fluoxetine Link_out
ATC Codes
  • N06AB03
AHFS Codes
  • 28:16.04.20
PDB Entries Not Available
FDA label show (194 KB)
MSDS show (76.7 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol The SSRI, fluoxetine, increases the effect of anticoagulant, acenocoumarol.
Almotriptan Increased risk of CNS adverse effects
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.
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.
Amphetamine Risk of serotoninergic syndrome
Anisindione The SSRI, fluoxetine, increases the effect of anticoagulant, anisindione.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
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 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.
Carvedilol The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
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.
Clarithromycin Possible serotoninergic syndrome with this combination
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.
Clozapine The antidepressant increases the effect of clozapine
Cyclosporine The antidepressant increases the effect and toxicity of cyclosporine
Cyproheptadine Possible antagonism of action
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.
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dexfenfluramine Risk of serotoninergic syndrome
Dextroamphetamine Risk of serotoninergic syndrome
Dextromethorphan Combination associated with possible serotoninergic syndrome
Dicumarol The SSRI, fluoxetine, increases the effect of anticoagulant, dicumarol.
Diethylpropion Risk of serotoninergic syndrome
Dihydroergotamine Possible ergotism and severe ischemia 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.
Eletriptan Increased risk of CNS adverse effects
Ergotamine Possible ergotism and severe ischemia with this combination
Erythromycin Possible serotoninergic syndrome with this combination
Ethotoin Fluoxetine increases the effect of phenytoin
Fenfluramine Risk of serotoninergic syndrome
Fosphenytoin Fluoxetine increases the effect of phenytoin
Frovatriptan Increased risk of CNS adverse effects
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Iloperidone Fluoxetine is a strong CYP2D6 inhibitor that increases serum concentration of iloperidone. Reduce dose of iloperidone by 50%
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.
Isocarboxazid Possible severe adverse reaction with this combination
Josamycin Possible serotoninergic syndrome 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 Linezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.
Lithium The SSRI, fluoxetine, increases serum levels of lithium.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mazindol Risk of serotoninergic syndrome
Mephenytoin Fluoxetine increases the effect of phenytoin
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Methamphetamine Risk of serotoninergic syndrome
Metoprolol The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, metoprolol.
Moclobemide Risk of serotoninergic syndrome
Naratriptan Increased risk of CNS adverse effects
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.
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 Fluoxetine increases the effect of phenytoin
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.
Propranolol The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, propranolol.
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.
Rasagiline Possible severe adverse reaction with this combination
Risperidone The SSRI, fluoxetine, increases the effect and toxicity of risperidone.
Ritonavir Increased risk of serotonin syndrome
Rizatriptan Increased risk of CNS adverse effects
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, fluoxetine.
Sumatriptan Increased risk of CNS adverse effects
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.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tamoxifen Fluoxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
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.
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.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
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.
Tiaprofenic acid Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
Tipranavir Tipranavir increases the concentration of Fluoxetine. The Fluoxetine dose may require an adjustment.
Tizanidine Fluoxetine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
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.
Tolmetin Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
Tolterodine Fluoxetine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
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.
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.
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, Fluoxetine. Monitor for increased bleeding during concomitant thearpy.
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.
Triprolidine The CNS depressants, Triprolidine and Fluoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Troleandomycin Possible serotoninergic syndrome with this combination
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Warfarin The SSRI, fluoxetine, increases the effect of anticoagulant, warfarin.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
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.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation and nausea.
Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Richman A, Heinrichs SC: Seizure prophylaxis in an animal model of epilepsy by dietary fluoxetine supplementation. Epilepsy Res. 2007 Apr;74(1):19-27. Epub 2007 Jan 9. Pubmed
  2. Iceta R, Mesonero JE, Alcalde AI: Effect of long-term fluoxetine treatment on the human serotonin transporter in Caco-2 cells. Life Sci. 2007 Mar 27;80(16):1517-24. Epub 2007 Jan 20. Pubmed
  3. Mirza NR, Nielsen EO, Troelsen KB: Serotonin transporter density and anxiolytic-like effects of antidepressants in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):858-66. Epub 2007 Jan 30. Pubmed
  4. Sanders AC, Hussain AJ, Hen R, Zhuang X: Chronic Blockade or Constitutive Deletion of the Serotonin Transporter Reduces Operant Responding for Food Reward. Neuropsychopharmacology. 2007 Mar 14;. Pubmed
  5. Goren MZ, Kucukibrahimoglu E, Berkman K, Terzioglu B: Fluoxetine partly exerts its actions through GABA: a neurochemical evidence. Neurochem Res. 2007 Sep;32(9):1559-65. Epub 2007 May 8. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: substrate, inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. Pubmed
  2. Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. Pubmed
  3. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression] Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. Pubmed
  4. Rasmussen BB, Brosen K: Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors? Ther Drug Monit. 2000 Apr;22(2):143-54. Pubmed
  5. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  6. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  7. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression] Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. CYP2B protein

Actions: inhibitor
UniProt ID: Q14097 Link_out
Gene: CYP2B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Haduch A, Wojcikowski J, Daniel WA: Effect of selected antidepressant drugs on cytochrome P450 2B (CYP2B) in rat liver. An in vitro and in vivo study. Pharmacol Rep. 2008 Nov-Dec;60(6):957-65. Pubmed

5. Cytochrome P450 1A2

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression] Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression] Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. Pubmed
  2. DeVane CL, Donovan JL, Liston HL, Markowitz JS, Cheng KT, Risch SC, Willard L: Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 2004 Feb;24(1):4-10. Pubmed
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2B6

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Margolis JM, O’Donnell JP, Mankowski DC, Ekins S, Obach RS:®-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab Dispos. 2000 Oct;28(10):1187-91. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19