Fluoxetine (Prozac)

Primer

Fluoxetine (Trade name: Prozac) is an antidepressant in the selective serotonin reuptake inhibitor (SSRI) class commonly used in the treatment of major depressive disorder, anxiety disorders, and eating disorders.

Pharmacokinetics

Pharmacokinetics of Fluoxetine

Absorption Reasonably bioavailable, peaks in 6 to 8 hours
Distribution 95% bound to protein
Metabolism Extensively metabolized by the liver to norfluoxetine, the only active metabolite
Elimination Primarily eliminated via hepatic metabolism to inactive metabolites, which are then excreted by the kidney.
Half-life 1 to 3 days after acute administration, and increases to 4 to 6 days after chronic use.

Fluoxetine: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 2D6
Induces
Inhibits 1A2, 2D6 (potent!), 3A4

Pharmacodynamics

Mechanism of Action

  • Primarily inhibition of SERT, but also mild NET inhibition
  • 5-HT2C antagonism may cause mild activating effects

Toxicity

Indications

Dosing

Dosing for Fluoxetine

Starting 20 mg PO daily
Titration Increase between 10 to 20 mg every 1 to 2 weeks depending on tolerability
Maximum 80 mg PO daily
Taper Low risk of withdrawal symptoms due to long half-life

Formulations

  • Fluoxetine comes in

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

  • Concomitant administration of fluoxetine and risperidone may increase the plasma concentration of risperidone by 2-3 fold through CYP2D6 inhibition.[1]

Side Effects

Adverse Events

Clinical Pearls

  • Fluoxetine has an active metabolite with long half-life, making it helpful in patients who are forgetful and miss doses!
  • Both fluoxetine and norfluoxetine (metabolite) inhibit their own hepatic metabolism, thus, repeated administration of fluoxetine causes the half-life to continue to increase.[2]
  • If a patient is experiencing antidepressant withdrawal with a potent antidepressant such as venlafaxine or paroxetine, one can start fluoxetine for 2 weeks to help with tapering (e.g. fluoxetine 10 mg x 2 days after stopping the first antidepressant)

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

Medically Ill

Resources

References

1) Spina, E., Avenoso, A., Scordo, M. G., Ancione, M., Madia, A., Gatti, G., & Perucca, E. (2002). Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: a clinically relevant pharmacokinetic drug interaction. Journal of clinical psychopharmacology, 22(4), 419-423.
2) van Harten, J. (1993). Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clinical pharmacokinetics, 24(3), 203-220.