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

See also article: Introduction to Pharmacology

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.

See also article: Cytochrome (CYP) P450 Metabolism

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

Serotonin syndrome

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

See main article: Geriatric Pharmacology

Pediatric

See main article: Pediatric Pharmacology

Obstetric and Fetal

See main article: Obstetric and Fetal Pharmacology

Medically Ill

See main article: Psychotropic Dosing in the Medically Ill

Resources

YouTube: Prozac - Revolution in a Capsule (Retro Report)

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.

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