Can Bupropion (Wellbutrin) be administered in the presence of acute hepatic toxicity?

From the Guidelines

Wellbutrin should not be given to patients with acute liver toxicity. This medication is metabolized by the liver, and impaired liver function can lead to increased blood levels of the drug, potentially causing serious side effects or toxicity 1. Patients with acute liver injury may experience reduced clearance of Wellbutrin, leading to accumulation of the drug and its metabolites in the body. The risk of seizures, which is already a concern with Wellbutrin, may be further increased in the setting of liver dysfunction.

Key Considerations

• The American Association for the Study of Liver Diseases (AASLD) recommends discontinuing all but essential medications in the setting of acute liver failure due to possible drug hepatotoxicity 1.
• Alternative antidepressant medications that are less dependent on hepatic metabolism, such as certain selective serotonin reuptake inhibitors (SSRIs), may be safer options for patients with liver impairment.
• All medications should be used cautiously in patients with liver impairment, and liver function tests should be monitored regularly.

Clinical Implications

• Once the acute liver toxicity has resolved and liver function has normalized, Wellbutrin therapy could potentially be reconsidered, but this should only be done under close medical supervision 1.
• It is essential to weigh the potential benefits of Wellbutrin against the risks of liver toxicity and to consider alternative treatment options that may be safer for patients with liver impairment.

From the FDA Drug Label

The elimination of the major metabolites of bupropion may be affected by reduced renal or hepatic function, because they are moderately polar compounds and are likely to undergo further metabolism or conjugation in the liver prior to urinary excretion Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys. The effect of hepatic impairment on the pharmacokinetics of bupropion was characterized in 2 single-dose trials, one in subjects with alcoholic liver disease and one in subjects with mild to severe cirrhosis In addition, in patients with severe hepatic cirrhosis, the bupropion C max and AUC were substantially increased (mean difference: by approximately 70% and 3-fold, respectively) and more variable when compared to values in healthy volunteers; the mean bupropion half-life was also longer (29 hours in subjects with severe hepatic cirrhosis vs. 19 hours in healthy subjects)

Key Points:

• Bupropion is extensively metabolized in the liver to active metabolites.
• Hepatic impairment can affect the pharmacokinetics of bupropion.
• In patients with severe hepatic cirrhosis, bupropion C max and AUC were substantially increased.
• The mean bupropion half-life was also longer in patients with severe hepatic cirrhosis.

Bupropion should be used with caution in patients with hepatic impairment. The drug label recommends considering a reduced frequency and/or dose in these patients 2.

From the Research

Wellbutrin and Acute Liver Toxicity

• Wellbutrin, also known as bupropion, is an antidepressant that can cause hepatotoxicity in some patients 3.
• The mechanism of bupropion-induced hepatotoxicity is considered to be predominantly immune-mediated, with a short latency period of 1-6 weeks 3.
• According to a case report, bupropion-induced hepatotoxicity can occur rapidly, with significant derangement of liver transaminases after just 6 days of treatment 3.
• The incidence of bupropion-induced hepatotoxicity is quoted to affect between 0.1% and 1% of treated patients, with either a hepatocellular and/or cholestatic pattern of damage 3.

Monitoring and Management

• Monitoring of liver function tests is crucial when prescribing bupropion, as most cases of hepatic damage are reversible when detected early 4, 3.
• Immediate discontinuation of bupropion is recommended upon abnormal lab findings or signs and symptoms of liver dysfunction 4, 3.
• Understanding drug-induced liver injury associated with antidepressants, including bupropion, is essential to optimize outcomes for antidepressant treatment 4.

Comparison with Other Hepatotoxic Agents

• Unlike acetaminophen, which can cause severe liver injury and acute liver failure after intentional and unintentional overdoses, bupropion-induced hepatotoxicity is considered a rare adverse effect 5.
• Other antidepressants, such as paroxetine, fluoxetine, and sertraline, have also been associated with hepatotoxicity, although the incidence and mechanisms may differ from bupropion 4, 6.