What is the half-life of Prozac (fluoxetine) 20mg?

Half-Life of Fluoxetine 20 mg

Fluoxetine (Prozac) 20 mg has an elimination half-life of 1 to 3 days after acute administration and 4 to 6 days after chronic administration, while its active metabolite norfluoxetine has a much longer half-life of 4 to 16 days. 1

Pharmacokinetic Profile

The pharmacokinetics of fluoxetine are characterized by:

• Initial half-life: 1-3 days for fluoxetine after acute administration 1
• Chronic administration half-life: 4-6 days for fluoxetine 1
• Norfluoxetine half-life: 4-16 days (average 7-15 days) 2, 3
• Metabolism: Primarily hepatic metabolism to inactive metabolites excreted by the kidney 1

Clinical Implications

The long elimination half-lives of fluoxetine and norfluoxetine have several important clinical implications:

• Drug accumulation: Significant accumulation occurs with chronic use, leading to delayed attainment of steady state even with fixed dosing 1
• Steady state timing: Steady state is typically reached after 4-5 weeks of treatment 1
• Persistence after discontinuation: Active drug remains in the body for weeks after stopping treatment 1
• Washout period: At least 5 weeks should be allowed after stopping fluoxetine before starting an MAOI due to the risk of serious drug interactions 4

Special Considerations

CYP2D6 Metabolism Variability

• Approximately 7% of the population are "poor metabolizers" due to reduced CYP2D6 enzyme activity 1
• Poor metabolizers achieve higher concentrations of S-fluoxetine but similar total active enantiomer concentrations 1
• Fluoxetine itself inhibits CYP2D6, potentially converting extensive metabolizers to poor metabolizers with continued use 5

Plasma Concentrations

After 30 days of dosing at 40 mg/day:

• Fluoxetine plasma concentrations: 91-302 ng/mL
• Norfluoxetine plasma concentrations: 72-258 ng/mL 1

Therapeutic Drug Monitoring Considerations

• Blood collection for therapeutic drug monitoring should occur at least 5 drug half-lives after dose changes 5
• For most antidepressants, sampling should occur immediately before the morning dose (12-16 hours after last dose)
• For fluoxetine specifically, the timing is less critical due to its long half-life 5

Common Pitfalls and Caveats

1. Drug interactions: The long half-life increases the risk of drug interactions even weeks after discontinuation 1

2. Dose adjustments: Due to the long half-life, changes in dose will not be fully reflected in plasma levels for several weeks 1

3. Liver disease: Elimination half-life is prolonged in patients with cirrhosis (mean 7.6 days for fluoxetine), requiring lower or less frequent dosing 1

4. Nonlinear pharmacokinetics: Fluoxetine exhibits nonlinear pharmacokinetics, meaning plasma concentrations may be higher than predicted by single-dose studies 1, 6

5. Age effects: Unlike many other antidepressants, fluoxetine pharmacokinetics are not significantly affected by age in elderly patients 7

The extended half-life of fluoxetine and its active metabolite may provide advantages for patients with poor medication adherence but requires careful consideration when switching to other medications, particularly those with potential for serotonergic interactions.