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Identification
NameFluoxetine
Accession NumberDB00472  (APRD00530)
Typesmall molecule
Groupsapproved
Description

Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). Fluoxetine is a racemic mixture of the R- and S- enantiomers and are of equivalent pharmacologic activity. 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. Fluoxetine 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
Synonyms
SynonymLanguageCode
(+-)-N-Methyl-3-phenyl-3-((alpha,alpha,alpha-trifluoro-P-tolyl)oxy)propylamineNot AvailableNot Available
(+-)-N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamineNot AvailableNot Available
FluoxetinGermanINN
FluoxetinaSpanishINN
FluoxétineFrenchINN
FluoxetinumLatinINN
ProzacNot AvailableNot Available
Salts
Name/CAS Structure Properties
Fluoxetine Hydrochloride
Thumb
  • InChI Key: GIYXAJPCNFJEHY-UHFFFAOYNA-N
  • Monoisotopic Mass: 345.110726557
  • Average Mass: 345.787
DBSALT000087
Brand names
NameCompany
AdofenBrainpharma
Animex-OnLaboratorios
FluoxerenMenarini
FontexLilly
LadoseLilly
ProzacDista
SarafemLilly
Brand mixtures
Brand NameIngredients
Symbyax Olanzapine + Fluoxetine
Categories
CAS number54910-89-3
WeightAverage: 309.3261
Monoisotopic: 309.134048818
Chemical FormulaC17H18F3NO
InChI KeyRTHCYVBBDHJXIQ-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenylpropylamines
Direct parentPhenylpropylamines
Alternative parentsBenzylethers; Phenol Ethers; Alkyl Aryl Ethers; Dialkylamines; Polyamines; Alkyl Fluorides; Organofluorides
Substituentsphenol ether; alkyl aryl ether; polyamine; ether; secondary aliphatic amine; secondary amine; organohalogen; organofluoride; amine; alkyl halide; alkyl fluoride; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropylamines. These are compounds containing a phenylpropylamine moiety, which consists of a phenyl group substituted at the third carbon by an propan-1-amine.
Pharmacology
IndicationLabeled 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.
PharmacodynamicsFluoxetine, 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. Antagonism of muscarinic, histaminergic, and α1–adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of classical tricyclic antidepressant (TCA) drugs. Fluoxetine binds to these and other membrane receptors from brain tissue much less potently in vitro than do the tricyclic drugs.
Mechanism of actionMetabolized 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.
AbsorptionWell absorbed from the GI tract following oral administration. Oral bioavailability is estimated to be at least 60-80%. Peak plasma concentrations occur within 6-8 hours following a single oral administration of a 40 mg dose. The oral solution and delayed-release capsule are bioequivalent. Food does not affect the systemic bioavailability of fluoxetine but it delays the absorption by 1-2 hours (not clinically significant). Prozac Weekly capsules, a delayed–release formulation, contain enteric–coated pellets that resist dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. The enteric coating delays the onset of absorption of fluoxetine 1 to 2 hours relative to the immediate–release formulations.
Volume of distribution
  • 20-45 L/kg
Protein binding94.5% bound to human serum proteins, including albumin and alpha-1-glycoprotein.
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.

SubstrateEnzymesProduct
Fluoxetine
NorfluoxetineDetails
Fluoxetine
para-TrifluoromethylphenolDetails
Fluoxetine
Hippuric acidDetails
Fluoxetine
Fluoxetine glucuronideDetails
Norfluoxetine
Norfluoxetine glucuronideDetails
Norfluoxetine
Not Available
Norfluoxetine alcoholDetails
Norfluoxetine alcohol
Not Available
Norfluoxetine acidDetails
Route of eliminationThe primary route of elimination appears to be hepatic metabolism to inactive metabolites excreted by the kidney. The S-enantiomer is eliminated more slowly and is the predominant enantiomer present at steady state.
Half life1-3 days [acute administration]; 4-6 days [chronic administration]; 4-16 days [norfluoxetine, acute and chronic administration].
ClearanceNot Available
ToxicitySymptoms 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
PathwayCategorySMPDB ID
Fluoxetine Action PathwayDrug actionSMP00426
Fluoxetine Metabolism PathwayDrug metabolismSMP00646
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.983
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.5899
P-glycoprotein inhibitor I Inhibitor 0.8565
P-glycoprotein inhibitor II Inhibitor 0.5459
Renal organic cation transporter Inhibitor 0.5633
CYP450 2C9 substrate Non-substrate 0.7475
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.5754
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Inhibitor 0.8993
CYP450 3A4 substrate Inhibitor 0.7959
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7149
Ames test Non AMES toxic 0.7105
Carcinogenicity Non-carcinogens 0.8089
Biodegradation Not ready biodegradable 0.9868
Rat acute toxicity 2.6048 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.6058
hERG inhibition (predictor II) Inhibitor 0.8467
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
FormRouteStrength
CapsuleOral10 mg, 20 mg, 40 mg
Capsule, delayed releaseOral90 mg
SolutionOral20 mg/5 mL
TabletOral10 mg, 20 mg, 60 mg
Prices
Unit descriptionCostUnit
PROzac 20 mg/5ml Solution 120ml Bottle266.51USDbottle
PROzac Weekly 1 Package = 4 capsule (90 mg) Disp Pack140.77USDdisp
Sarafem 7 10 mg tablet Box61.08USDbox
Sarafem 7 20 mg tablet Each Box Contains 7 tablet59.55USDbox
Prozac weekly 90 mg capsule34.5USDcapsule
PROzac 40 mg capsule13.89USDcapsule
Fluoxetine hcl powder8.32USDg
Sarafem 10 mg tablet7.91USDtablet
Sarafem 15 mg tablet7.91USDtablet
Sarafem 20 mg tablet7.91USDtablet
PROzac 20 mg capsule6.95USDcapsule
PROzac 10 mg capsule6.77USDcapsule
FLUoxetine HCl 40 mg capsule5.54USDcapsule
PROzac 10 mg tablet4.31USDtablet
Fluoxetine hcl 20 mg tablet4.26USDtablet
Rapiflux 20 mg tablet3.11USDtablet
FLUoxetine HCl 20 mg capsule2.77USDcapsule
Fluoxetine hcl 10 mg tablet2.72USDtablet
FLUoxetine HCl 10 mg capsule2.7USDcapsule
Fxt 40 40 mg Capsule2.3USDcapsule
Prozac 10 mg Capsule2.02USDcapsule
Prozac 20 mg Capsule2.02USDcapsule
Apo-Fluoxetine 10 mg Capsule1.13USDcapsule
Co Fluoxetine 10 mg Capsule1.13USDcapsule
Mylan-Fluoxetine 10 mg Capsule1.13USDcapsule
Novo-Fluoxetine 10 mg Capsule1.13USDcapsule
Nu-Fluoxetine 10 mg Capsule1.13USDcapsule
Phl-Fluoxetine 10 mg Capsule1.13USDcapsule
Pms-Fluoxetine 10 mg Capsule1.13USDcapsule
Ratio-Fluoxetine Hydrochloride 10 mg Capsule1.13USDcapsule
Sandoz Fluoxetine 10 mg Capsule1.13USDcapsule
Apo-Fluoxetine 20 mg Capsule1.06USDcapsule
Co Fluoxetine 20 mg Capsule1.06USDcapsule
Mylan-Fluoxetine 20 mg Capsule1.06USDcapsule
Novo-Fluoxetine 20 mg Capsule1.06USDcapsule
Nu-Fluoxetine 20 mg Capsule1.06USDcapsule
Phl-Fluoxetine 20 mg Capsule1.06USDcapsule
Pms-Fluoxetine 20 mg Capsule1.06USDcapsule
Ratio-Fluoxetine Hydrochloride 20 mg Capsule1.06USDcapsule
Sandoz Fluoxetine 20 mg Capsule1.06USDcapsule
FLUoxetine HCl 20 mg/5ml Solution1.03USDml
Apo-Fluoxetine 4 mg/ml Liquid0.61USDliquid
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69605771997-11-012017-11-01
United States59103191997-05-292017-05-29
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point179-182 °CNot Available
water solubility50 mg/mL at 25 °CNot Available
logP4.05ADLARD,M ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility1.70e-03 g/lALOGPS
logP4.09ALOGPS
logP4.17ChemAxon
logS-5.3ALOGPS
pKa (strongest basic)9.8ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area21.26ChemAxon
rotatable bond count7ChemAxon
refractivity80.37ChemAxon
polarizability30.33ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Eduard Schwartz, Joseph Kaspi, Zinovi Itov, Gidon Pilarski, “Production of fluoxetine and new intermediates.” U.S. Patent US5225585, issued October, 1990.

US5225585
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
ResourceLink
KEGG DrugD00823
PubChem Compound3386
PubChem Substance46507902
ChemSpider3269
BindingDB30130
ChEBI5118
ChEMBLCHEMBL41
Therapeutic Targets DatabaseDAP000186
PharmGKBPA449673
IUPHAR203
Guide to Pharmacology203
Drug Product Database2242124
RxListhttp://www.rxlist.com/cgi/generic/fluoxetine.htm
Drugs.comhttp://www.drugs.com/fluoxetine.html
WikipediaFluoxetine
ATC CodesN06AB03
AHFS Codes
  • 28:16.04.20
PDB EntriesNot Available
FDA labelshow(194 KB)
MSDSshow(76.7 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe SSRI, fluoxetine, increases the effect of anticoagulant, acenocoumarol.
AlmotriptanIncreased risk of CNS adverse effects
AmitriptylineThe 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.
AmoxapineThe 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.
AmphetamineRisk of serotoninergic syndrome
AnisindioneThe SSRI, fluoxetine, increases the effect of anticoagulant, anisindione.
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AstemizoleIncreased risk of cardiotoxicity and arrhythmias
AtomoxetineThe CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
BenzphetamineAmphetamines 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.
CarbamazepineCarbamazepine 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.
CarvedilolThe SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
CilostazolFluoxetine, 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.
ClarithromycinPossible serotoninergic syndrome with this combination
ClomipramineThe 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.
ClozapineThe antidepressant increases the effect of clozapine
CyclosporineThe antidepressant increases the effect and toxicity of cyclosporine
CyproheptadinePossible antagonism of action
DesipramineThe 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.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DexfenfluramineRisk of serotoninergic syndrome
DextroamphetamineRisk of serotoninergic syndrome
DextromethorphanCombination associated with possible serotoninergic syndrome
DicoumarolThe SSRI, fluoxetine, increases the effect of anticoagulant, dicumarol.
DiethylpropionRisk of serotoninergic syndrome
DihydroergotaminePossible ergotism and severe ischemia with this combination
DoxepinThe 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.
EletriptanIncreased risk of CNS adverse effects
ErgotaminePossible ergotism and severe ischemia with this combination
ErythromycinPossible serotoninergic syndrome with this combination
EthotoinFluoxetine increases the effect of phenytoin
FenfluramineRisk of serotoninergic syndrome
FosphenytoinFluoxetine increases the effect of phenytoin
FrovatriptanIncreased risk of CNS adverse effects
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
IloperidoneFluoxetine is a strong CYP2D6 inhibitor that increases serum concentration of iloperidone. Reduce dose of iloperidone by 50%
ImipramineThe 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.
Insulin LisproConcomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
IsocarboxazidPossible severe adverse reaction with this combination
JosamycinPossible serotoninergic syndrome with this combination
KetoprofenConcomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.
LinezolidLinezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.
LithiumThe SSRI, fluoxetine, increases serum levels of lithium.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MazindolRisk of serotoninergic syndrome
MephenytoinFluoxetine increases the effect of phenytoin
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MethamphetamineRisk of serotoninergic syndrome
MetoprololThe SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, metoprolol.
MoclobemideRisk of serotoninergic syndrome
NaratriptanIncreased risk of CNS adverse effects
NortriptylineThe 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.
OxycodoneIncreased risk of serotonin syndrome
PhendimetrazineRisk of serotoninergic syndrome
PhenelzinePossible severe adverse reaction with this combination
PhentermineRisk of serotoninergic syndrome
PhenylpropanolamineRisk of serotoninergic syndrome
PhenytoinFluoxetine increases the effect of phenytoin
PropafenoneAdditive 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.
PropranololThe SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, propranolol.
ProtriptylineThe 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.
RasagilinePossible severe adverse reaction with this combination
RisperidoneThe SSRI, fluoxetine, increases the effect and toxicity of risperidone.
RitonavirIncreased risk of serotonin syndrome
RizatriptanIncreased risk of CNS adverse effects
SelegilinePossible severe adverse reaction with this combination
SibutramineRisk of serotoninergic syndrome
St. John's WortSt. John's Wort increases the effect and toxicity of the SSRI, fluoxetine.
SumatriptanIncreased risk of CNS adverse effects
TacrineThe 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.
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TamoxifenFluoxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
TamsulosinFluoxetine, 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.
TerbinafineTerbinafine 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.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
TetrabenazineStrong CYP2D6 inhibitors may increase exposure of the metabolites of tetrabenazine. Consider a reduction of dose.
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tiaprofenic acidAdditive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
TipranavirTipranavir increases the concentration of Fluoxetine. The Fluoxetine dose may require an adjustment.
TizanidineFluoxetine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
TolbutamideTolbutamide, 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.
TolmetinIncreased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
TolterodineFluoxetine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
ToremifeneAdditive 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.
TramadolThe 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.
TranylcypromineIncreased 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.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TreprostinilThe prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Fluoxetine. Monitor for increased bleeding during concomitant thearpy.
TrimipramineThe 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.
TriprolidineThe CNS depressants, Triprolidine and Fluoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
TroleandomycinPossible serotoninergic syndrome with this combination
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
WarfarinThe SSRI, fluoxetine, increases the effect of anticoagulant, warfarin.
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZolmitriptanUse 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.
ZuclopenthixolAdditive 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.
Zuclopenthixol acetateAdditive 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.
Zuclopenthixol decanoateAdditive 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
CYP2B protein Q14097 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

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

8. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. 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

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. FDA label

2. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

References:

  1. FDA label

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10