How does duloxetine (Cymbalta) affect liver function tests (LFTs)?

From the Guidelines

Duloxetine can cause severe hepatotoxicity, including hepatic failure and cholestatic jaundice, and should be discontinued immediately if patients develop jaundice or other evidence of clinically significant liver dysfunction. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1, duloxetine has been associated with hepatic failure presenting as abdominal pain, hepatomegaly, and elevation of transaminase levels. The guideline also notes that cholestatic jaundice has been reported with duloxetine use.

Some key points to consider when prescribing duloxetine include:

• Duloxetine should be used cautiously in patients with pre-existing liver disease
• Monitoring of liver function tests is recommended before starting treatment and periodically thereafter, especially during the first few months
• Patients should be advised to report any symptoms of liver problems such as right upper quadrant pain, fatigue, dark urine, or yellowing of the skin or eyes
• The medication should be discontinued and not restarted in patients who develop jaundice or other evidence of clinically significant liver dysfunction, as noted in the guideline 1.

It is essential to weigh the potential benefits of duloxetine against the risks of hepatotoxicity, particularly in patients with pre-existing liver disease or those who consume substantial amounts of alcohol. The guideline emphasizes the importance of medical education, training, and experience in safely and effectively prescribing antidepressant medications like duloxetine 1.

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 increased the risk of elevation of serum transaminase levels in development program clinical trials. Liver transaminase elevations resulted in the discontinuation of 0. 3% (92/34,756) of duloxetine delayed-release capsules-treated patients. In adult placebo-controlled trials, for patients with normal and abnormal baseline ALT values, elevation of ALT >3 times the ULN occurred in 1.25% (144/11,496) of duloxetine delayed-release capsules-treated patients compared to 0. 45% (39/8716) of placebo-treated patients.

Duloxetine can affect liver function tests (LFTs) by causing:

• Elevation of transaminase levels
• Hepatic failure (sometimes fatal)
• Hepatitis with abdominal pain, hepatomegaly, and jaundice The risk of LFT abnormalities is higher in patients with:
• Substantial alcohol use
• Evidence of chronic liver disease
• Concomitant medications that induce orthostatic hypotension or are potent CYP1A2 inhibitors
• Doses above 60 mg daily 2

From the Research

Duloxetine's Effect on Liver Function Tests (LFTs)

Duloxetine, also known by its brand name Cymbalta, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, and neuropathic pain. The effect of duloxetine on liver function tests (LFTs) has been a subject of study due to reports of liver injury associated with its use.

Key Findings

• A study published in 2008 3 found that while duloxetine can cause elevations in liver enzymes in a small fraction of patients, the risk of hepatic toxicity is rare (estimated 1-2 per 100,000 exposures) and generally resolves spontaneously without any change in treatment.
• However, other studies have reported cases of duloxetine-induced liver injury, including a case report from 2021 4 that recommends monitoring LFTs when initiating or adjusting the dose of duloxetine to facilitate early identification and management of potential liver injury.
• A case report from 2010 5 described a patient who developed cholestatic jaundice after 5 months of duloxetine treatment, highlighting the need for careful monitoring of liver function in patients taking this medication.
• Another case report from 2006 6 described a patient who developed fulminant hepatic failure after increasing her duloxetine dose, resulting in death.
• A case-series study from 2010 7 described seven patients with suspected duloxetine hepatotoxicity, with six cases assessed as definite or very likely, and found that duloxetine hepatotoxicity can develop within 2 months of drug intake and lead to clinically significant liver injury.

Risk Factors and Recommendations

• Patients with preexisting liver disease and/or substantial alcohol use may be at higher risk of liver injury from duloxetine 3, 6.
• Monitoring LFTs is recommended when initiating or adjusting the dose of duloxetine, and intermittently thereafter, to facilitate early identification and management of potential liver injury 4, 5.
• Clinicians should be aware of the potential for duloxetine-induced liver injury and carefully monitor liver function in patients taking this medication 3, 4, 5, 6, 7.