Fluoxetine

Aka: Fluoxetine, Prozac, Prozac Weekly, Sarafem

1. Mechanism
   1. Selective Serotonin Reuptake Inhibitor (SSRI)
2. Indications
   1. Major Depression (especially with Hypersomnia)
   2. Obsessive Compulsive Disorder
   3. Bulimia Nervosa
   4. Premenstrual Dysphoric Disorder (Premenstrual Syndrome)
3. Background
   1. Tablets are generic with cost as low as $26 per month
4. 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
5. Dosing
   1. Daily
      1. Start
         1. Children (age 7 to 18 years): 5-10 mg qd
         2. Adults: 20 mg PO qd
         3. Elderly: 10 mg qd
      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 PO qd
         3. Maximal dose often required in Bulimia and OCD
   2. Weekly
      1. Prozac Weekly 90 mg once weekly
         1. Equivalent to 20 mg qd
6. Pharmacokinetics
   1. Half Life is Very Long! (7-9 days)
   2. Therapeutic Blood level 163-560 ng/ml
7. Drug Interactions
   1. See Serotonin Syndrome
   2. Stop for 5 weeks before starting MAO inhibitor
   3. Inhibits Cytochrome P450-3A and P450-2D6
   4. Highly protein bound
      1. Interacts with other protein bound medications
   5. Raises the following drug levels
      1. Warfarin (Coumadin) and increased INR
      2. Tricyclic Antidepressants
      3. Carbamazepine (Tegretol)
      4. Phenytoin (Dilantin)
8. Adverse Effects: General
   1. Activating on the Sedation to excitation continuum
      1. Most activation or aggravation of all SSRIs
   2. Anxiety or nervousness
   3. Akathisia
   4. Insomnia
      1. Consider Trazodone (Desyrel) at bedtime
   5. Avoid in the elderly
   6. Weight loss may occur
9. 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]
10. Resources
    1. Prozac Website (Lilly)
       1. http://www.prozac.com