Fluoxetine


Description

Fluoxetine is a 2nd generation antidepressant categorized as a selective serotonin reuptake inhibitor (SSRI).[

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Pharmacology

Indication

Fluoxetine is indicated for both acute and maintenance treatment of major depressive disorder, obses... Read more

Pharmacodynamic

Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately r... Read more

Mechanism of action

The monoaminergic hypothesis of depression emerged in 1965 and linked depression with dysfunction of... Read more

Absorption

The oral bioavailability of fluoxetine is Read more

Protein binding

Approximately 94% of fluoxetine is plasma protein bound.[ Read more

Volume of distribution

The volume of distribution of fluoxetine and it's metabolite varies between 20 to 42 L/kg.[ Read more

Clearance

The clearance value of fluoxetine in healthy patients is reported to be 9.6 ml/min/kg.[ Read more

Half life

The half life of fluoxetine is significant with the elimination half-life of the parent drug averagi... Read more

Route of elimination

Fluoxetine is primarily eliminated in the urine.[ Read more

Toxicity

In a report that included 234 fluoxetine overdose cases, it was concluded that symptoms resulting fr... Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Insomnia US
  • Kind: experimental
    • Percent: 33%
  • Kind: placebo
    • Percent: 13%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 29%
  • Kind: placebo
    • Percent: 11%
  • Clinical Trial
    Insomnia US
  • Kind: experimental
    • Percent: 28%
  • Kind: placebo
    • Percent: 22%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 26%
  • Kind: placebo
    • Percent: 13%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 21%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 21%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 18%
  • Kind: placebo
    • Percent: 13%
  • Clinical Trial
    Somnolence US
  • Kind: experimental
    • Percent: 17%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 17%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Decreased appetite US
  • Kind: experimental
    • Percent: 17%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Insomnia US
  • Kind: experimental
    • Percent: 16%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 11%
  • Clinical Trial
    Anxiety US
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Nervousness US
  • Kind: experimental
    • Percent: 14%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Anxiety US
  • Kind: experimental
    • Percent: 14%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Somnolence US
  • Kind: experimental
    • Percent: 13%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Somnolence US
  • Kind: experimental
    • Percent: 13%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Tremor US
  • Kind: experimental
    • Percent: 13%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Anxiety US
  • Kind: experimental
    • Percent: 12%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 12%
  • Kind: placebo
    • Percent: 8%
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 12%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 12%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Pharyngitis US
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Decreased libido US
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Weight Loss US
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 0.5%
  • Clinical Trial
    Nervousness US
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Yawn US
  • Kind: experimental
    • Percent: 11%
  • Clinical Trial
    Tremor US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Flu syndrome US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Pharyngitis US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Insomnia US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 7%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 9%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Tremor US
  • Kind: experimental
    • Percent: 9%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 9%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 9%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Sweating US
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Flu syndrome US
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Sweating US
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Abnormal ejaculation US
  • Kind: experimental
    • Percent: 7%
  • Clinical Trial
    Sweating US
  • Kind: experimental
    • Percent: 7%
  • Clinical Trial
    Yawn US
  • Kind: experimental
    • Percent: 7%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 7%
  • Clinical Trial
    Allergic Reactions US
  • Kind: experimental
    • Percent: 7%
  • Clinical Trial

    Contraindications

    • Time Period: Avoid concomitant use. Avoid thioridazine within 5 weeks of fluoxetine discontinuation.
    • Regions: US
    • With Drugs:
        • Name: Thioridazine
        • Drugbank Id: DB00679
    • Regions: US
    • With Drugs:
        • Name: Pimozide
        • Drugbank Id: DB01100
    • Time Period: Avoid initiating fluoxetine in patient's being treated with intravenous methylene blue.
    • Regions: US
    • With Drugs:
        • Name: Methylene blue
        • Drugbank Id: DB09241
    • Time Period: Avoid initiating fluoxetine in patient's being treated with linezolid.
    • Regions: US
    • With Drugs:
        • Name: Linezolid
        • Drugbank Id: DB00601
    • Time Period: Avoid administration of monoamine oxidase inhibitors (MAOI) with fluoxetine or within 5 weeks of fluoxetine discontinuation. Avoid fluoxetine within 14 days of discontinuing a MAOI.
    • Regions: US
    • With Categories:
        • Name: Monoamine Oxidase Inhibitors
        • Drugbank Id: DBCAT001004
        • Mesh Id: D008996

    Food Interactions

    • Avoid alcohol.
    • Take with food to reduce irritation and nausea.

    Interactions

    Type in a drug name to check for interaction with Fluoxetine

    The serum concentration of (R)-warfarin can be increased when it is combined with Fluoxetine.
    The serum concentration of (S)-Warfarin can be increased when it is combined with Fluoxetine.
    The therapeutic efficacy of Fluoxetine can be decreased when used in combination with 1,10-Phenanthroline.
    The risk or severity of hypoglycemia can be increased when Fluoxetine is combined with 2,4-thiazolidinedione.
    The risk or severity of serotonin syndrome can be increased when Fluoxetine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
    The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Fluoxetine.
    The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Fluoxetine.
    The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Fluoxetine.
    The risk or severity of adverse effects can be increased when Fluoxetine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
    The risk or severity of hemorrhage can be increased when Fluoxetine is combined with 4-hydroxycoumarin.
    The risk or severity of adverse effects can be increased when Fluoxetine is combined with 4-Methoxyamphetamine.
    The metabolism of 5-androstenedione can be decreased when combined with Fluoxetine.
    The risk or severity of adverse effects can be increased when 5-methoxy-N,N-dimethyltryptamine is combined with Fluoxetine.
    The metabolism of Fluoxetine can be decreased when combined with 6-Deoxyerythronolide B.
    The metabolism of 6-O-benzylguanine can be decreased when combined with Fluoxetine.
    The metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Fluoxetine.
    The risk or severity of adverse effects can be increased when Fluoxetine is combined with 7-Nitroindazole.
    7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Fluoxetine.
    The metabolism of 8-azaguanine can be decreased when combined with Fluoxetine.
    The metabolism of 8-chlorotheophylline can be decreased when combined with Fluoxetine.

    References

    • 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: 7623609]
    • 2 . Sommi RW, Crismon ML, Bowden CL: Fluoxetine: a serotonin-specific, second-generation antidepressant. Pharmacotherapy. 1987 Jan-Feb;7(1):1-15. [PubMed: 3554156]
    • 3 . Sohel AJ, Molla M: Fluoxetine . [PubMed: 29083803]
    • 4 . Suchard JR: Fluoxetine overdose-induced seizure. West J Emerg Med. 2008 Aug;9(3):154-6. [PubMed: 19561732]
    • 5 . Borys DJ, Setzer SC, Ling LJ, Reisdorf JJ, Day LC, Krenzelok EP: Acute fluoxetine overdose: a report of 234 cases. Am J Emerg Med. 1992 Mar;10(2):115-20. [PubMed: 1586402]
    • 6 . Lee-Kelland R, Zehra S, Mappa P: Fluoxetine overdose in a teenager resulting in serotonin syndrome, seizure and delayed onset rhabdomyolysis. BMJ Case Rep. 2018 Oct 8;2018. pii: bcr-2018-225529. doi: 10.1136/bcr-2018-225529. [PubMed: 30301727]
    • 7 . Schenker S, Bergstrom RF, Wolen RL, Lemberger L: Fluoxetine disposition and elimination in cirrhosis. Clin Pharmacol Ther. 1988 Sep;44(3):353-9. doi: 10.1038/clpt.1988.161. [PubMed: 3262026]
    • 8 . Margolis JM, O'Donnell JP, Mankowski DC, Ekins S, Obach RS: (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab Dispos. 2000 Oct;28(10):1187-91. [PubMed: 10997938]
    • 9 . Liu ZQ, Zhu B, Tan YF, Tan ZR, Wang LS, Huang SL, Shu Y, Zhou HH: O-Dealkylation of fluoxetine in relation to CYP2C19 gene dose and involvement of CYP3A4 in human liver microsomes. J Pharmacol Exp Ther. 2002 Jan;300(1):105-11. doi: 10.1124/jpet.300.1.105. [PubMed: 11752104]
    • 10 . Crifasi JA, Le NX, Long C: Simultaneous identification and quantitation of fluoxetine and its metabolite, norfluoxetine, in biological samples by GC-MS. J Anal Toxicol. 1997 Oct;21(6):415-9. doi: 10.1093/jat/21.6.415. [PubMed: 9323519]
    • 11 . Shi S, Liu Y, Wu J, Li Z, Zhao Y, Zhong D, Zeng F: Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study. Clin Ther. 2010 Oct;32(11):1977-86. doi: 10.1016/j.clinthera.2010.10.003. [PubMed: 21095492]
    • 12 . Prozac FDA Label [Link]
    • 13 . Fluoxetine: A case history of its discovery and preclinical development [Link]
    • 14 . The Distribution of Fluoxetine in Human Fluids and Tissues [Link]
    • 15 . DailyMed - Fluoxetine [Link]
    • 16 . Flockhart Table of Drug Interactions [Link]

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