Does fluoxetine (Prozac) affect liver function?

From the Guidelines

Fluoxetine can affect liver function, though serious liver problems are uncommon, and individuals with pre-existing liver disease should use it cautiously. This antidepressant is processed by the liver, and in some people, it may cause mild elevations in liver enzymes that typically don't require stopping treatment 1. The evidence suggests that fluoxetine may be associated with hepatotoxicity, although the risk is scarce 1. According to a study published in 2008, second-generation antidepressants, including fluoxetine, may have similar adverse effects, with nausea and vomiting being the most common reasons for discontinuation in efficacy studies 1.

Key Considerations

• Individuals with pre-existing liver disease should use fluoxetine cautiously, as the drug may accumulate in their system due to reduced metabolism.
• Those taking fluoxetine should be aware of warning signs of liver problems, including yellowing of the skin or eyes, dark urine, upper right abdominal pain, or unusual fatigue.
• Regular liver function monitoring is recommended for patients with liver disease or those taking other medications that affect the liver.
• The typical adult dose of fluoxetine ranges from 20-80 mg daily, and the medication should never be stopped abruptly as this can cause withdrawal symptoms.

Recommendations

• If you have concerns about fluoxetine and your liver, consult your healthcare provider before making any changes to your medication regimen.
• Be aware of the potential risks and benefits of fluoxetine, and discuss them with your healthcare provider to determine the best course of treatment for your specific condition.
• Monitoring of liver function is essential for patients taking fluoxetine, especially those with pre-existing liver disease, to minimize the risk of hepatotoxicity 1.

From the FDA Drug Label

Liver disease — As might be predicted from its primary site of metabolism, liver impairment can affect the elimination of fluoxetine. The elimination half–life of fluoxetine was prolonged in a study of cirrhotic patients, with a mean of 7. 6 days compared with the range of 2 to 3 days seen in subjects without liver disease; norfluoxetine elimination was also delayed, with a mean duration of 12 days for cirrhotic patients compared with the range of 7 to 9 days in normal subjects. This suggests that the use of fluoxetine in patients with liver disease must be approached with caution If fluoxetine is administered to patients with liver disease, a lower or less frequent dose should be used (see PRECAUTIONS and DOSAGE AND ADMINISTRATION)

Yes, fluoxetine can affect liver function. Liver impairment can affect the elimination of fluoxetine, leading to prolonged elimination half-lives.

• The elimination half-life of fluoxetine is prolonged in patients with liver disease, such as cirrhosis.
• Patients with liver disease may require a lower or less frequent dose of fluoxetine 2.

From the Research

Effect of Fluoxetine on Liver Function

• Fluoxetine is primarily eliminated through hepatic metabolism, with the formation of a pharmacologically active demethylated product, norfluoxetine 3.
• The elimination of fluoxetine is significantly reduced in patients with stable alcoholic cirrhosis, resulting in higher concentrations of fluoxetine and norfluoxetine at steady state 3.
• Fluoxetine-induced hepatotoxicity is generally considered to be of minimal clinical importance, but asymptomatic increases in liver enzyme values have been observed in 0.5% of patients taking long-term fluoxetine therapy 4.
• There have been reported cases of acute hepatitis believed to be caused by fluoxetine, with the mechanism of hepatotoxicity unknown 4, 5.

Incidence of Liver Injury

• The incidence of drug-induced liver injury during antidepressant treatment is relatively low, with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine having a lower probability of liver injury compared to other antidepressants 6.
• The incidence of liver injury associated with fluoxetine is approximately 0.02% 6.
• Common clinical symptoms of drug-induced liver injury include nausea, fatigue, loss of appetite, and abdominal pain 6.

Mechanism of Liver Injury

• The mechanism of fluoxetine-induced liver injury is not fully understood, but it is believed to involve the inhibition of ferroptosis, a form of programmed cell death 7.
• The ATF3/FSP1 signaling pathway has been identified as a key mediator of fluoxetine-induced liver injury, with co-catalpol alleviating liver injury through the inhibition of this pathway 7.