What medications can be used to lower elevated bilirubin levels?

Medications to Lower Bilirubin

There are no FDA-approved medications that directly lower bilirubin levels in adults; treatment focuses on addressing the underlying cause of hyperbilirubinemia rather than pharmacologically reducing bilirubin itself. 1

Neonatal Hyperbilirubinemia: Phototherapy as Primary Treatment

Phototherapy is the definitive treatment for neonatal hyperbilirubinemia, not medication. 2

• Intensive phototherapy using blue-green wavelength light (460-490 nm, optimal peak 478 nm) at irradiance of 25-35 mW/cm²/nm can decrease bilirubin by 30-40% within 24 hours in newborns ≥35 weeks gestation 2
• For extremely high bilirubin levels (>30 mg/dL), intensive phototherapy can produce a decline of up to 10 mg/dL within a few hours, with decreases of 0.5-1 mg/dL per hour expected in the first 4-8 hours 2
• LED light sources are preferred because they deliver specific wavelengths in narrow bandwidths with minimal heat generation 2

Adjunctive Measures in Neonates

• Milk-based formula supplementation (not medication) inhibits enterohepatic circulation of bilirubin and helps lower serum bilirubin in mildly dehydrated infants 2
• Maintaining adequate hydration improves phototherapy efficacy since photo-products are excreted in urine and bile 2
• Exchange transfusion is indicated when phototherapy fails, not pharmacologic intervention 2

Investigational Agent: Tin-Mesoporphyrin

• Tin-mesoporphyrin (a heme oxygenase inhibitor) has evidence for preventing or treating hyperbilirubinemia, but is NOT FDA-approved 2
• If approved, it could prevent the need for exchange transfusion in infants not responding to phototherapy 2

Adult Hyperbilirubinemia: Treat the Underlying Cause

The management strategy depends entirely on whether hyperbilirubinemia is conjugated or unconjugated, and addressing the root cause rather than using bilirubin-lowering drugs. 1

Unconjugated Hyperbilirubinemia

• Gilbert syndrome (most common cause of isolated mild unconjugated hyperbilirubinemia) requires no treatment and patients should be fully reassured 1
• For hemolysis-induced hyperbilirubinemia, treat the underlying hemolytic process (G6PD deficiency, hereditary spherocytosis, etc.) rather than the bilirubin itself 2
• Medication-induced unconjugated hyperbilirubinemia requires discontinuation or modification of the offending agent (e.g., antivirals causing hemolysis or impaired conjugation) 3

Conjugated Hyperbilirubinemia

• Biliary obstruction requires procedural intervention (ERCP, stenting, surgery) to relieve obstruction, not medication 2
• Hepatocellular injury from autoimmune hepatitis responds to immunosuppression (prednisone/prednisolone plus azathioprine), which treats the underlying disease rather than directly lowering bilirubin 2
• Drug-induced liver injury requires immediate discontinuation of the hepatotoxic medication when bilirubin ≥2× baseline with ALT ≥3× ULN 2

Cancer-Related Hyperbilirubinemia

• In hepatocellular carcinoma, sorafenib should be used with caution in patients with elevated bilirubin levels due to increased toxicity risk 2
• For biliary tract cancers with moderately elevated bilirubin from endoluminal disease, cisplatin-gemcitibine may be considered despite optimal stenting, but this treats the cancer, not the bilirubin 2

Critical Clinical Pitfalls

• Never use medications to "lower bilirubin" without first determining if it is conjugated or unconjugated 1
• In antiviral therapy causing hyperbilirubinemia, modification of drug choice or dose may be required for liver injury or brisk hemolysis, but mild indirect hyperbilirubinemia from impaired conjugation is well-tolerated and requires no intervention 3
• Avoid overinterpreting isolated mild unconjugated hyperbilirubinemia as significant liver disease—Gilbert syndrome is benign and requires no treatment 1
• In drug-induced cholestatic liver injury during clinical trials, an episode resulting in hepatic decompensation should trigger permanent drug discontinuation 2