Half-Life of Fluoxetine 10 mg
Fluoxetine has an elimination half-life of 1-3 days after acute administration and 4-6 days after chronic administration, while its active metabolite norfluoxetine has an even longer half-life of 4-16 days. 1
Pharmacokinetic Properties of Fluoxetine
Fluoxetine (Prozac) has one of the longest half-lives among antidepressants, which has important clinical implications:
- Initial (acute) administration: 1-3 days half-life 1
- Chronic administration: 4-6 days half-life 1
- Active metabolite (norfluoxetine): 4-16 days half-life 1, 2
The pharmacokinetic profile of fluoxetine is characterized by:
- Extensive metabolism in the liver to norfluoxetine (formed by demethylation) 1
- Norfluoxetine is a more potent and selective serotonin reuptake inhibitor than fluoxetine itself 3
- Protein binding of approximately 94.5% 1
- Nonlinear pharmacokinetics (metabolism is not proportional to dose) 1
Clinical Implications of Long Half-Life
The long elimination half-life of fluoxetine and norfluoxetine leads to:
- Significant accumulation with chronic use - After 30 days of dosing at 40 mg/day, plasma concentrations reach 91-302 ng/mL for fluoxetine and 72-258 ng/mL for norfluoxetine 1
- Delayed attainment of steady state - Even with fixed dosing 1
- Persistence in the body for weeks after discontinuation - This depends on individual patient characteristics, previous dosing regimen, and length of therapy 1
Advantages:
- Reduced risk of withdrawal symptoms upon missed doses or discontinuation 2
- Potential benefit for patients with poor medication adherence 2
- Possibility of once-weekly dosing in maintenance treatment 4
Disadvantages:
- Long washout period (5 weeks) required before starting medications that might interact with fluoxetine 2
- Delayed resolution of adverse effects if they occur 5
- Prolonged drug-drug interaction potential even after discontinuation 1
Special Considerations
- Liver disease: Half-life is prolonged in cirrhotic patients (mean 7.6 days for fluoxetine and 12 days for norfluoxetine) 1
- CYP2D6 poor metabolizers: May achieve higher concentrations of S-fluoxetine but total active enantiomer concentration remains similar to normal metabolizers 1
- Drug interactions: Due to inhibition of CYP2D6, fluoxetine may interact with other medications metabolized by this enzyme 1
The long half-life of fluoxetine is unique among SSRIs and should be considered when initiating therapy, changing doses, discontinuing treatment, or switching to other medications, particularly those with potential for serotonergic interactions.