What is the half-life of Paxil (paroxetine)?

Half-Life of Paroxetine (Paxil)

The elimination half-life of paroxetine (Paxil) is approximately 21 hours after oral dosing, allowing for once-daily administration. 1

Pharmacokinetic Details

• Paroxetine reaches steady-state concentrations in approximately 10 days for most patients, although it may take substantially longer in some individuals 1
• The half-life is consistent across multiple dosing studies, with the FDA label reporting a mean elimination half-life of approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days 1
• Paroxetine exhibits nonlinear pharmacokinetics with increasing doses, reflecting saturation of metabolic pathways 1
• The drug is extensively metabolized after oral administration, primarily through the CYP2D6 enzyme pathway 1

Special Populations and Half-Life Variations

• In elderly patients, Cmin concentrations are about 70-80% greater than in non-elderly subjects, suggesting slower elimination and potentially longer half-life 1
• Patients with severe renal impairment (creatinine clearance below 30 mL/min) show approximately 4 times greater plasma concentrations 1
• Patients with moderate renal impairment (creatinine clearance 30-60 mL/min) and those with hepatic functional impairment show about a 2-fold increase in plasma concentrations 1
• These changes in drug exposure necessitate dose adjustments in these populations 1

Clinical Implications of Paroxetine's Half-Life

• The 21-hour half-life allows for once-daily dosing, which is shorter than some other SSRIs like fluoxetine (2-4 days, with active metabolite 7-15 days) 2
• Paroxetine has no active metabolites, unlike fluoxetine, which contributes to its predictable pharmacokinetic profile 3
• The half-life of paroxetine is long enough to minimize fluctuations in blood levels between doses but not so long as to cause excessive accumulation with standard dosing 4
• When discontinuing paroxetine, its moderate half-life means that a gradual taper is recommended to minimize withdrawal symptoms, typically over 10-14 days 5

Practical Considerations

• Paroxetine's half-life is shorter than some other SSRIs like fluoxetine, which may increase the risk of discontinuation symptoms if doses are missed or the medication is abruptly stopped 2
• The drug reaches steady state in 4-14 days, which should be considered when evaluating initial treatment response 4
• Due to its role as both a substrate and inhibitor of CYP2D6, paroxetine may interact with other medications metabolized by this enzyme 1, 4
• The half-life of paroxetine is not affected by food intake, although food can increase the Cmax by approximately 29% 1

Understanding paroxetine's half-life is important for appropriate dosing, anticipating the time to reach steady state, and planning for medication discontinuation to minimize withdrawal effects.