Can Cymbalta (duloxetine) cause liver damage?

From the Guidelines

Cymbalta (duloxetine) can cause liver damage, and patients should be closely monitored for signs of liver dysfunction, particularly during the first few months of treatment. According to a 2020 clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders, published in the Journal of the American Academy of Child and Adolescent Psychiatry 1, duloxetine has been associated with hepatic failure presenting as abdominal pain, hepatomegaly, and elevation of transaminase levels. Key points to consider include:

• Duloxetine should be discontinued and not restarted in patients who develop jaundice or other evidence of clinically significant liver dysfunction
• Cholestatic jaundice has also been reported in patients taking duloxetine
• Patients with pre-existing liver disease should exercise caution when taking Cymbalta, and regular liver function tests may be recommended for those with risk factors
• Warning signs of liver problems include yellowing of skin or eyes, dark urine, upper right abdominal pain, or unexplained fatigue, and patients should seek medical attention immediately if they experience any of these symptoms. The mechanism behind Cymbalta-induced liver damage isn't fully understood but may involve metabolic idiosyncratic reactions, as noted in the study 1. Most cases of liver injury resolve after discontinuation of the medication.

From the FDA Drug Label

There have been reports of hepatic failure, sometimes fatal, in patients treated with duloxetine delayed-release capsules. These cases have presented as hepatitis with abdominal pain, hepatomegaly, and elevation of transaminase levels to more than twenty times the upper limit of normal (ULN) with or without jaundice, reflecting a mixed or hepatocellular pattern of liver injury Duloxetine delayed-release capsules should be discontinued in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established. Liver transaminase elevations resulted in the discontinuation of 0.3% (92/34,756) of duloxetine delayed-release capsules-treated patients. Because it is possible that duloxetine delayed-release capsules and alcohol may interact to cause liver injury or that duloxetine delayed-release capsules may aggravate pre-existing liver disease, duloxetine delayed-release capsules should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease.

Yes, Cymbalta (duloxetine) can cause liver damage.

• Key points:
  • Hepatic failure, sometimes fatal, has been reported in patients treated with duloxetine.
  • Duloxetine should be discontinued in patients who develop jaundice or other evidence of clinically significant liver dysfunction.
  • Liver transaminase elevations have resulted in the discontinuation of duloxetine in some patients.
  • Duloxetine should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease. 2

From the Research

Liver Damage Associated with Cymbalta (Duloxetine)

• Cymbalta (duloxetine) has been reported to cause liver damage in some patients, although the incidence is rare 3, 4, 5.
• Elevations in liver enzymes have been observed in a small fraction of patients treated with duloxetine, which generally resolve spontaneously without any change in treatment 3.
• Very rare cases (estimated 1-2 per 100,000 exposures) of idiosyncratic hepatic toxicity have been reported in patients taking duloxetine, particularly in those with substantial alcohol use and/or preexisting liver disease 3.
• Fulminant hepatic failure has been reported in some cases, including a patient who developed subacute injury and died after taking duloxetine 5.

Risk Factors and Monitoring

• Patients with preexisting liver disease and those who consume substantial amounts of alcohol may be at higher risk of developing liver damage while taking duloxetine 3, 5.
• Some studies recommend monitoring liver function tests (LFTs) when initiating or adjusting the dose of duloxetine, and intermittently thereafter, to facilitate early identification and management of potential liver injury 4.
• However, other studies suggest that systematic monitoring of liver aminotransferases may not be warranted with routine duloxetine use 3, 6.

Comparison with Other Antidepressants

• Duloxetine does not appear to pose a greater hazard for hepatic toxicity when compared to other conventional antidepressants 6.
• Selective serotonin reuptake inhibitors (SSRIs) may be less likely to precipitate drug-induced liver injury compared to other antidepressants, including duloxetine 7.