Can Prozac (fluoxetine) increase total bilirubin and albumin levels?

Can Prozac Increase Total Bilirubin and Albumin Levels?

Prozac (fluoxetine) can cause elevations in total bilirubin through drug-induced hepatotoxicity, but it does not increase albumin levels—in fact, hepatotoxicity would decrease albumin production if liver synthetic function is impaired.

Bilirubin Elevation with Fluoxetine

Evidence of Hepatotoxicity

• Fluoxetine can cause acute hepatitis, though this is uncommon and not well recognized clinically 1
• Asymptomatic increases in liver enzyme values occur in approximately 0.5% of patients on long-term fluoxetine therapy 1
• Five documented cases of acute hepatitis caused by fluoxetine have been reported in the literature, demonstrating that clinically significant hepatotoxicity can occur 1
• The mechanism of fluoxetine-induced hepatotoxicity remains unknown 1

Clinical Implications

• Drug-induced liver injury should be considered in any patient with unexplained hyperbilirubinemia, and all medications including fluoxetine should be reviewed for potential hepatotoxicity 2, 3
• Physicians should maintain clinical vigilance for fluoxetine-associated hepatitis and consider early discontinuation if suspected 1
• When bilirubin elevation occurs with fluoxetine, it typically reflects hepatocellular injury rather than isolated transporter inhibition, unlike drugs such as indinavir that selectively inhibit bilirubin transporters 4

Albumin Levels with Fluoxetine

Why Albumin Does Not Increase

• Albumin is produced exclusively in the liver and serves as a marker of hepatic synthetic function 5
• If fluoxetine causes hepatotoxicity severe enough to elevate bilirubin, albumin levels would decrease, not increase, as liver synthetic capacity becomes impaired 5
• Albumin concentrations below 3.5 g/dL indicate reduced hepatic synthetic function and are used in scoring systems like Child-Pugh to assess liver disease severity 5

Context for Albumin Interpretation

• Albumin levels can be reduced in many non-hepatic conditions including sepsis, systemic inflammatory disorders, nephrotic syndrome, malabsorption, and gastrointestinal protein loss 5
• Overinterpretation of albumin as solely reflecting liver disease severity is not warranted without considering the clinical context 5

Monitoring Recommendations

When to Suspect Fluoxetine Hepatotoxicity

• Monitor for symptoms of hepatitis including jaundice, right upper quadrant pain, nausea, or fatigue 1
• Check liver function tests (ALT, AST, alkaline phosphatase, GGT, total and conjugated bilirubin, albumin) if hepatotoxicity is suspected 5, 2
• Routine monitoring of liver function in all patients on fluoxetine may not be cost-effective, but targeted monitoring based on clinical suspicion is appropriate 1

Diagnostic Approach for Hyperbilirubinemia

• Determine whether hyperbilirubinemia is predominantly conjugated or unconjugated to narrow differential diagnosis 5, 2
• Drug-induced liver injury typically presents with elevated liver enzymes and conjugated hyperbilirubinemia 3
• Ultrasound is the initial imaging study of choice if biliary obstruction or parenchymal liver disease is suspected 2

Important Caveats

• The incidence of clinically significant fluoxetine hepatotoxicity is low (0.5% with asymptomatic enzyme elevations) 1
• Most patients tolerate fluoxetine without hepatic complications 1
• If bilirubin elevation occurs during fluoxetine therapy, other causes of hyperbilirubinemia (viral hepatitis, alcohol, other medications, biliary obstruction) must be systematically excluded 2, 3
• Early discontinuation of fluoxetine is recommended if drug-induced hepatitis is suspected 1