What is the initial treatment for Wilson's disease?

Initial Treatment for Wilson's Disease

Trientine is the recommended initial treatment for Wilson's disease due to its effectiveness and better safety profile compared to D-penicillamine. 1

Treatment Options Overview

Wilson's disease is a genetic disorder of copper metabolism that requires lifelong treatment. The main therapeutic approaches include:

1. Chelation therapy - removes excess copper from the body

   • D-penicillamine
   • Trientine
   • Tetrathiomolybdate (experimental)

2. Zinc therapy - blocks intestinal copper absorption

   • Primarily used for maintenance therapy

First-Line Treatment Recommendations

Trientine

• Dosage: 750-1500 mg/day in 2-3 divided doses 1
• Pediatric dosing: 20 mg/kg/day rounded to nearest 250 mg in 2-3 divided doses 1
• Administration: Take 1 hour before or 2-3 hours after meals 1
• Advantages:
  • Effective initial therapy even for patients with decompensated liver disease 1
  • Significantly fewer side effects than D-penicillamine 1
  • Lower incidence of neurological worsening (less common than with D-penicillamine) 1

D-Penicillamine (Alternative First-Line)

• Dosage: Start with 250 mg/day and gradually increase to 750-1500 mg/day in 2-4 divided doses 1
• Pediatric dosing: 20 mg/kg/day 1
• Administration: 1 hour before meals or 2 hours after meals 1
• Limitations:
  • High rate of adverse effects (approximately 30% of patients) 1
  • Neurological worsening occurs in 10-50% of patients during initial treatment 1
  • Early sensitivity reactions can occur within 1-3 weeks 1

Monitoring Treatment Efficacy

• 24-hour urinary copper excretion:

  • Initial treatment: May exceed 1000 μg (16 μmol) per day 1
  • Maintenance: Should be 200-500 μg (3-8 μmol) per day 1
  • Values <200 μg/day may indicate non-adherence or overtreatment 1

• Non-ceruloplasmin bound copper: Should normalize with effective treatment 1

• Clinical parameters: Monitor liver function tests and neurological status 1

Special Considerations

For Patients with Neurological Symptoms

• Caution with D-penicillamine: Higher risk of neurological worsening (13.8% of patients) 1
• Preferred approach: Start with trientine due to lower risk of neurological deterioration 1

For Patients with Liver Disease

• Trientine has been shown to be effective for patients with decompensated liver disease 1
• Recovery of liver function typically occurs within 2-6 months of treatment initiation 1

For Asymptomatic/Presymptomatic Patients

• Both chelating agents (trientine, D-penicillamine) or zinc can be effective 1
• Zinc may be preferable for presymptomatic children due to better safety profile 1

Maintenance Therapy

After initial chelation therapy and stabilization:

• Zinc therapy can be considered for maintenance treatment 2
• Zinc dosage: 150 mg/day in three divided doses for adults 1
• Mechanism: Induces intestinal metallothionein, blocking copper absorption 1, 3

Common Pitfalls to Avoid

1. Discontinuation of therapy: Can lead to disease progression and liver failure within 1-12 months 1

2. Inadequate monitoring: Regular assessment of copper excretion and non-ceruloplasmin bound copper is essential 1

3. Coadministration issues:

   • Avoid iron supplements with trientine (forms toxic complex) 1
   • Take medication away from meals to ensure proper absorption 1

4. Failure to recognize adverse effects early:

   • Monitor for proteinuria, hematuria, rash, or cytopenia 1, 4
   • Immediately discontinue D-penicillamine if early sensitivity reactions occur 1

Wilson's disease treatment is lifelong, and the goal is to normalize free copper in serum to prevent progressive organ damage and improve quality of life 3.