Is sertraline (Zoloft) metabolized by the liver?

From the Guidelines

Yes, sertraline (Zoloft) is metabolized by the liver, specifically through the cytochrome P450 enzyme system, which may require dose adjustments in patients with hepatic impairment. The liver metabolism of sertraline is a crucial aspect of its pharmacokinetics, as it undergoes extensive first-pass metabolism, converting it into its primary metabolite, N-desmethylsertraline, which is significantly less active than the parent compound 1.

Key Points

• Sertraline's liver metabolism involves the cytochrome P450 enzyme system, including CYP2B6, CYP2C19, CYP2C9, CYP3A4, and CYP2D6.
• Patients with hepatic impairment may experience higher blood levels of sertraline due to decreased clearance, necessitating dose adjustments.
• The half-life of sertraline is approximately 26 hours, allowing for once-daily dosing.
• Liver metabolism creates potential drug interactions with medications that inhibit or induce cytochrome enzymes, requiring closer monitoring in patients with liver disease or those taking affected medications.

Clinical Implications

The liver metabolism of sertraline has significant clinical implications, particularly in patients with hepatic impairment or those taking medications that interact with the cytochrome P450 enzyme system. Close monitoring and potential dose adjustments are necessary to minimize adverse effects and ensure therapeutic efficacy. According to the most recent and highest quality study available, sertraline's metabolism by the liver is a critical consideration in its clinical use 1.

From the FDA Drug Label

Sertraline is extensively metabolized by the liver. In patients with chronic mild liver impairment, sertraline clearance was reduced, resulting in increased AUC, Cmax and elimination half-life Liver impairment can affect the elimination of sertraline In patients with chronic mild liver impairment who received 50 mg sertraline per day maintained for 21 days, sertraline clearance was reduced, resulting in approximately 3-fold greater exposure compared to age-matched volunteers with no hepatic impairment

Yes, sertraline (Zoloft) is metabolized by the liver.

• Key points:
  • Sertraline is extensively metabolized by the liver 2
  • Liver impairment can affect the elimination of sertraline 2
  • Patients with liver disease should be approached with caution when administering sertraline 2 2

From the Research

Metabolism of Sertraline

• Sertraline is metabolized in the liver by the cytochrome P450 (CYP) enzyme system 3
• The specific CYP isozymes involved in the biotransformation of sertraline are not fully understood, but CYP3A has been claimed to be involved in the biotransformation of sertraline to norsertraline 4
• Sertraline may cause significant inhibition of CYP2D6, but only at high doses 3

Comparison with Other SSRIs

• Unlike some other SSRIs, such as fluoxetine and paroxetine, sertraline is not a potent inhibitor of CYP2D6 5, 4
• Sertraline is also not a potent inhibitor of CYP1A2, CYP2C19, or CYP3A4, unlike some other SSRIs such as fluvoxamine and nefazodone 5, 4, 3

Clinical Implications

• The metabolism of sertraline in the liver may be affected by concomitant intake of inhibitors or inducers of the CYP isozymes involved in its biotransformation 3
• Monitoring of liver function tests is crucial when using sertraline, as it has been associated with hepatotoxicity in some cases 6