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fluoxetine (Prozac, Sarafem)

Tradenames: Prozac, Sarafem. Indications: - major depression* - obsessive compulsive disorder - panic/anxiety attacks - premenstrual dysphoric disorder (PMDD) (Sarafem) - bulimia nervosa, anorexia nervosa - seasonal affective disorder - postpartum depression - bipolar disorder, mania [11] - post-traumatic stress disorder (PTSD) - obesity - hot flashes secondary to anti-estrogen or anti-androgen therapy [5] - self-injurious behavior - fibromyalgia [11] - narcolepsy [11] * may be less effective with in hospitalized elderly & patients with post-stroke depression * OK for children [8] * physicians, but NOT children rated fluoxetine better than placebo [9] Dosage: - start 5-20 mg PO QD, increase by 10-20 mg every 4 weeks - optimal dosage for major depression is 20 mg QD [13] - according to NEJM, 20 mg is not optimal dose [15] - max 80 mg/day. - doses > 20 mg/day should be divided BID. Tabs: 10 & 20 mg. Liquid 20 mg/5 mL, Liquid doses available. Prozac Weekly: 1) 90 mg delayed release capsule 2) weekly dosing for patients stabilized on 20 mg QD Pharmacokinetics: 1) well absorbed orally 2) onset of action 1-4 weeks 3) maximum antidepressant effects generally occur > 4 weeks 4) metabolized to an active metabolite norfluoxetine by cyt P450 2D6 5) long 1/life among antidepressants - 1/2life is initially 1-3 days, increasing to 4-5 days after multiple daily doses - metabolite norfluoxetine 1/2life is 7-15 days - 1/2life is increased in patients with cirrhosis 6) eliminated in the urine Adverse effects: 1) common (> 10%) 1) anxiety 2) diarrhea 3) headache 4) insomnia 5) nausea 6) sexual dysfunction (ejaculation problems, inorgasmia) - substitute with or add bupropion [15] 7) slight drowsiness 2) less common (1-10%) - abnormal dreams, chest pain, constipation, anorexia, weight loss, dizziness, dry mouth, frequent urination, menstrual pain, stuffy nose, weakness, tremor, vomiting, diaphoresis - hyperprolactinemia 3) other [3,6] a) sedation (rare) b) asthenia c) rash d) SIADH & hyponatremia, more likely in combination with a thiazide diuretic [4] e) worsening of paranoia (rare) f) bradycardia with syncope has been reported in the elderly g) fluoxetine exacerbates restless legs syndrome [10] h) fluoxetine exacerbates periodic limb movment disorder [10] i) bruxism [4] j) fluoxetine is associated with congenital birth defects but absolute risk is small [12] - ventricular septal defects - right ventricular outflow tract obstruction cardiac defects - craniosynostosis k) QTc prolongation Because of the long 1/2 life, resolution of adverse effects after discontinuation of fluoxetine may be slow Drug interactions: 1) monoamine oxidase (MAO) inhibitors - hyperpyrexia, tremor, seizures, delirium, coma can occur 2) tryptophan - increased CNS & GI side effects, 3) fluoxetine inhibits cyt P450 2D6 & to a lesser extent 3A4, 2C19 thus inhibits its own metabolism a) tricyclic antidepressants b) terfenadine c) astemizole d) cisapride e) trazodone f) carbamazepine g) phenytoin h) diazepam i) oxycodone [14] 4) ondansetron & other drugs that prolong QTc interval 5) fluoxetine decreases central hypotensive effects of clonidine 6) fluoxetine potentiate toxicity of class IC antiarrhythmic agents 7) fluoxetine may displace highly protein-bound drugs 8) ritonavir (Norvir, Kaletra) in combination may result in serotonin syndrome Laboratory: 1) specimen: a) serum, plasma b) stable at 4 degrees C for 19 months 2) methods: HPLC, GC-EC 3) labs with Loincs - fluoxetine in specimen - fluoxetine in body fluid - fluoxetine in gastric fluid - fluoxetine in serum/plasma - fluoxetine in urine Mechanism of action: 1) selective serotonin re-uptake inhibitor (SSRI) 2) fluoxetine inhibits cyt P450 2D6 Comparative biology: - fluoxetine can induce a juvenile-like state in specific types of neurons in the prefrontal cortex, hippocampal dentate gyrus, basolateral amygdala, & visual cortex of adult mice

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) fluoxetine in serum/plasma

General

amine selective serotonin reuptake inhibitor (SSRI)

Properties

MISC-INFO: elimination route LIVER 1/2life 26-220 HOURS protein-binding 95% elimination by hemodialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, American College of Physicians, Philadelphia 1998, 2012
  5. Prescriber's Letter 7(2):11, Feb. 2000
  6. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  7. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  8. Prescriber's Letter 10(10):57 2003 Detail-Document#: 191003 (subscription needed) http://www.prescribersletter.com
  9. Journal Watch 24(11):85, 2004 Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet. 2004 Apr 24;363(9418):1341-5. Review. PMID: 15110490 - Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004 Apr 10;328(7444):879-83. Review. No abstract available. Erratum in: BMJ. 2004 May 15;328(7449):1170. PMID: 15073072 http://bmj.bmjjournals.com/cgi/content/full/328/7444/879
  10. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  11. Deprecated Reference
  12. Reefhuis J et al Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. BMJ 2015;351:h3190 PMID: 26156519 http://www.bmj.com/content/351/bmj.h3190
  13. Jakubovski E et al. Systematic review and meta-analysis: Dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry 2015 Nov 10; PMID: 26552940 http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
  14. Yunusa I, Gagne JJ, Yoshida K et al Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors. JAMA Netw Open. 2022;5(2):e220194 PMID: 3520131 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789401
  15. NEJM Knowledge+ Psychiatry

Component-of

fluoxetine/olanzapine (Symbyax)