What medications are used to treat hyperbilirubinemia?

Medications for Hyperbilirubinemia Management

The treatment of hyperbilirubinemia depends on the underlying cause, patient age, and severity, with phototherapy being the primary intervention for neonatal hyperbilirubinemia, while specific medications targeting the underlying cause are used for adults.

Neonatal Hyperbilirubinemia Treatment

First-line Treatment

• Phototherapy is the cornerstone of treatment for neonatal hyperbilirubinemia 1
  • Blue-green wavelength light (460-490 nm) with peak at 478 nm
  • Minimum irradiance of 30 μW·cm⁻²·nm⁻¹
  • Should expose maximum body surface area (35-80% of skin)

Pharmacological Options

1. Intravenous Immunoglobulin (IVIG)

   • Dosage: 0.5-1 g/kg over 2 hours 1
   • Indication: Isoimmune hemolytic disease with rising TSB despite intensive phototherapy or TSB within 2-3 mg/dL of exchange level
   • Repeat in 12 hours if necessary

2. Phenobarbital

   • Reduces peak serum bilirubin, duration and need for phototherapy, and need for exchange transfusion in preterm neonates 2
   • Not routinely recommended as first-line therapy

3. Tin-mesoporphyrin (investigational)

   • Inhibits heme oxygenase production
   • Could prevent need for exchange transfusion in infants not responding to phototherapy 1
   • Not yet FDA approved

Severe Cases

• Exchange transfusion for extreme hyperbilirubinemia 1
  • Indicated when TSB ≥25 mg/dL (428 μmol/L) or ≥20 mg/dL (342 μmol/L) in sick infants
  • Should only be performed by trained personnel in NICU with full monitoring capabilities
  • Potential complications include apnea, bradycardia, cyanosis, vasospasm, thrombosis, and necrotizing enterocolitis

Adult Hyperbilirubinemia Treatment

Unconjugated Hyperbilirubinemia

• Treatment targets the underlying cause:
  • Hemolysis: Treat the underlying hemolytic condition 1
  • Gilbert syndrome: No specific treatment required (benign condition) 1

Conjugated Hyperbilirubinemia

1. Drug-induced hyperbilirubinemia

   • Discontinuation of the offending agent 3
   • Common culprits: acetaminophen, penicillin, oral contraceptives, anabolic steroids, chlorpromazine 1
   • For antiviral-induced hyperbilirubinemia: modification in drug choice or dose may be required 3

2. Autoimmune hepatitis

   • Prednisone/prednisolone followed by addition of azathioprine after two weeks 1
   • Initial prednisolone dose: typically 1 mg/kg
   • Azathioprine: Start at 50 mg/day, increase to maintenance dose of 1-2 mg/kg 1
   • Alternative in non-cirrhotic patients: Budesonide (9 mg/day) plus azathioprine 1

3. Spontaneous bacterial peritonitis with hyperbilirubinemia

   • Third-generation cephalosporins as first-line antibiotic treatment 1
   • Albumin administration (1.5 g/kg at diagnosis and 1 g/kg on day 3) decreases frequency of hepatorenal syndrome and improves survival 1

4. Biliary obstruction

   • Treat underlying cause (e.g., gallstones, tumor) 1
   • Endoscopic or surgical intervention may be required

Severe Refractory Cases

• Plasma exchange may be beneficial in patients with severe hyperbilirubinemia refractory to conventional treatments 4
  • Shown to significantly reduce both total and direct bilirubin levels
  • Consider when other treatment options have failed

Monitoring and Follow-up

For Neonates

• Frequency of TSB monitoring based on severity 5:

  • TSB ≥25 mg/dL: Recheck within 2-3 hours
  • TSB 20-25 mg/dL: Recheck within 3-4 hours
  • TSB <20 mg/dL: Recheck in 4-6 hours

• Discontinue phototherapy when 5:

  • TSB has declined 2-4 mg/dL below the threshold at which phototherapy was initiated
  • For readmitted infants, when TSB falls below 13-14 mg/dL

For Adults

• Monitor liver function tests, including direct and indirect bilirubin
• Follow-up frequency depends on underlying cause and severity

Important Considerations

• Always identify and treat the underlying cause of hyperbilirubinemia
• Distinguish between conjugated (direct) and unconjugated (indirect) hyperbilirubinemia to guide treatment
• In drug-induced hyperbilirubinemia, the decision to continue or discontinue therapy should be based on assessment of cause and risk-benefit analysis 3
• For neonates, ensure adequate hydration and feeding (every 2-3 hours) during treatment 1

Remember that treatment must be tailored to the specific type of hyperbilirubinemia and its underlying cause, with prompt intervention for severe cases to prevent complications such as kernicterus in neonates or progressive liver damage in adults.