Description

Simple

A medication used to treat major depression, obsessive compulsive disorder, and panic disorders.

Clinical

A selective serotonin reuptake inhibitor used to treat major depressive disorder, bulimia, OCD, premenstrual dysphoric disorder, panic disorder, and bipolar I.

Overview

Fluoxetine is a 2nd generation antidepressant categorized as a selective serotonin reuptake inhibitor (SSRI).[2] It gained FDA approval in 1987 and although it was initially intended for the treatment of depression, today it is commonly prescribed to manage depression in addition to various other pathologies.[13]

Pharmacology

Indication

Fluoxetine is indicated for both acute and maintenance treatment of major depressive disorder, obsessive compulsive disorder, and bulimia nervosa; however, it is only indicated for acute treatment of panic disorder independent of whether agoraphobia is present.[ Read more

Pharmacodynamic

Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas.[ Read more

Mechanism of action

The monoaminergic hypothesis of depression emerged in 1965 and linked depression with dysfunction of neurotransmitters such as noradrenaline and serotonin.[13] Indeed,... Read more

Absorption

The oral bioavailability of fluoxetine is Read more

Protein binding

Approximately 94% of fluoxetine is plasma protein bound.[2]

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 averaging 1-3 days after acute administration, and 4-6 days after chronic administration.[12] Further, the elimination half life... Read more

Route of elimination

Fluoxetine is primarily eliminated in the urine.[15]

Toxicity

In a report that included 234 fluoxetine overdose cases, it was concluded that symptoms resulting from fluoxetine overdose were generally minor and short in duration.[ Read more

Adverse Effects

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 or without food.

Interactions

Type in a drug name to check for interaction with Fluoxetine
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Fluoxetine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Fluoxetine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1,10-Phenanthroline
The therapeutic efficacy of Fluoxetine can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedione
The risk or severity of hypoglycemia can be increased when Fluoxetine is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of serotonin syndrome can be increased when Fluoxetine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Fluoxetine.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Fluoxetine.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Fluoxetine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Fluoxetine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The risk or severity of hemorrhage can be increased when Fluoxetine is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Fluoxetine.
5-methoxy-N,N-dimethyltryptamine
The metabolism of Fluoxetine can be decreased when combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be decreased when combined with Fluoxetine.
7-Nitroindazole
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
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Fluoxetine.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Fluoxetine.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Fluoxetine.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be decreased when combined with Fluoxetine.
9-Methylguanine
The metabolism of 9-Methylguanine can be decreased when combined with Fluoxetine.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Fluoxetine.
17 References
  1. 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. 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. 3 . Sohel AJ, Molla M: Fluoxetine .PubMed: 29083803
  4. 4 . Suchard JR: Fluoxetine overdose-induced seizure. West J Emerg Med. 2008 Aug;9(3):154-6.PubMed: 19561732
  5. 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. 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. 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. 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. 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. 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. 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. 12 . Prozac FDA Label Link
  13. 13 . Fluoxetine: A case history of its discovery and preclinical development Link
  14. 14 . The Distribution of Fluoxetine in Human Fluids and Tissues Link
  15. 15 . DailyMed - Fluoxetine Link
  16. 16 . Flockhart Table of Drug Interactions Link
  17. 17 . Health Canada Product Monograph: Fluoxetine oral capsules Link