Pharm

Fluoxetine

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Fluoxetine, Prozac, Prozac Weekly, Sarafem, Selemra

  • See Also
  1. Selective Serotonin Reuptake Inhibitor (SSRI)
  • Mechanism
  1. Selective Serotonin Reuptake Inhibitor (SSRI)
  • Indications
  1. Major Depression (especially with Hypersomnia)
  2. Obsessive Compulsive Disorder
  3. Bulimia Nervosa
  4. Premenstrual Dysphoric Disorder (Premenstrual Syndrome)
  • Background
  1. Capsules are less expensive than tablets, and both are generic
  • Safety
  1. Avoid in Lactation
    1. Fluoxetine levels are not high in Breast Milk
    2. However Fluoxetine is associated with more adverse effects in infants than other SSRIs
    3. Teratogenic if patient becomes pregnant again (therefore generally avoided in Lactation)
  2. Pregnancy Category C
    1. Well studied in pregnancy, but data in 2015 showed association with cardiac defects
    2. Association with VSD, right ventricular outflow tract obstruction cardiac defects, and Craniosynostosis
    3. Berard (2015) Br J Clin Pharmacol +PMID:26613360

  • Preparations
  1. Capsules: 10, 20 and 40 mg
  2. Tablets (scored): 10 mg
  3. Oral solution: 20 mg/5 ml
  4. Long-acting Prozac Weekly preparation: 90 mg capsules
  • Dosing
  1. Daily
    1. Start
      1. Children (age 7 to 18 years): 5-10 mg orally daily
      2. Adults: 20 mg orally daily
      3. Elderly: 10 mg orally daily
    2. Titrate
      1. Avoid increasing dose more often than monthly
    3. Maximum
      1. Children (age 7 to 18 years): 60 mg
      2. Adults: 80 mg orally daily
      3. Maximal dose often required in Bulimia and OCD
  2. Weekly (Delayed Release or DR formulation)
    1. Prozac Weekly 90 mg once weekly
      1. Equivalent to 20 mg orally daily
  • Pharmacokinetics
  1. Half Life is Very Long! (48 to 72 hours; duration 7-9 days)
  2. Therapeutic Blood level 163-560 ng/ml
  • Drug Interactions
  1. See Serotonin Syndrome
  2. Stop for 5 weeks before starting MAO Inhibitor
  3. Metabolized by Cytochrome P450-2D6 and 2C9
  4. Strong Cytochrome P450-2D6 Inhibitor
  5. Moderate Cytochrome P450-2C19 Inhibitor (increases Phenytoin levels)
  6. Highly Protein bound
    1. Interacts with other Protein bound medications
  7. Raises the following drug levels
    1. Warfarin (Coumadin) and increased INR
    2. Tricyclic Antidepressants
    3. Carbamazepine (Tegretol)
    4. Phenytoin (Dilantin)
  • Adverse Effects
  • General
  1. Discontinued in 15% of patients due to adverse effects
  2. Activating on the sedation to excitation continuum
    1. Most activation or aggravation of all SSRIs
  3. Anxiety or nervousness
  4. Akathisia
  5. Insomnia
    1. Consider Trazodone (Desyrel) at bedtime
  6. Avoid in the elderly
  7. Weight loss may occur
  • Adverse Effects
  • Pregnancy
  1. Earlier safety data
    1. Major Fetal Structural abnormality
      1. No Change (5.5% versus 4% for Placebo)
    2. Minor Fetal Structural abnormality
      1. Significant Association (15.5% vs 6.5% for Placebo)
    3. Fluoxetine also associated with
      1. Preterm Labor
      2. NICU admissions
      3. Low birth weight
    4. References: Study of n=482
      1. Chambers (1996) N Engl J Med 335:1010-5 [PubMed]
  2. Safety data in 2015
    1. Fluoxetine has been well studied in pregnancy, but data in 2015 showed association with cardiac defects
    2. Berard (2015) Br J Clin Pharmacol +PMID:26613360 [PubMed]
  • Resources
  1. Fluoxetine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=88989ab9-8143-404d-8488-67a289e525b4
  • References
  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia