Can hydroxyurea cause gastrointestinal discomfort and bleeding?

Hydroxyurea Can Cause Gastrointestinal Discomfort and Bleeding

Yes, hydroxyurea can cause gastrointestinal discomfort and bleeding as documented adverse effects. The FDA drug label specifically lists gastrointestinal symptoms including stomatitis, anorexia, nausea, vomiting, diarrhea, and constipation among the known toxicities of hydroxyurea 1.

Gastrointestinal Effects of Hydroxyurea

Common GI Adverse Effects

• Gastrointestinal discomfort including:
  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal cramps
  • Stomatitis (inflammation of the mouth)
  • Anorexia (loss of appetite)

Severe GI Adverse Effects

• Gastrointestinal bleeding
• Ulceration of the GI tract
• Pancreatitis (particularly in patients with HIV receiving antiretroviral drugs) 1

Evidence of GI Ulceration

Multiple case reports have documented hydroxyurea-associated ulcers in various parts of the gastrointestinal tract:

• Ileocecal valve ulceration that resolved upon discontinuation of hydroxyurea and recurred with rechallenge 2
• Colonic ulcers in patients with thalassemia 3
• Ulcerative lesions from the terminal ileum to the ascending colon that resolved within a month after discontinuing hydroxyurea 3

Risk Factors and Monitoring

Certain factors may increase the risk of gastrointestinal adverse effects:

• Higher doses of hydroxyurea (though GI effects can occur at standard doses)
• Concomitant use with other medications that can cause GI irritation
• Splenectomized patients appear to experience adverse effects of hydroxyurea more frequently 4
• Longer duration of therapy

Management Recommendations

When gastrointestinal symptoms occur:

1. Evaluate severity:

   • Mild symptoms may be managed with supportive care
   • Severe symptoms or evidence of bleeding require immediate attention

2. For mild GI discomfort:

   • Consider taking medication with food
   • Divide daily dose
   • Anti-emetics for nausea/vomiting
   • Antidiarrheal agents for diarrhea

3. For GI bleeding or severe symptoms:

   • Discontinue hydroxyurea immediately
   • Perform appropriate diagnostic evaluation (endoscopy may be required)
   • Consider alternative cytoreductive agents such as interferon-alpha or anagrelide 5

4. Monitoring:

   • Regular clinical assessment for GI symptoms
   • Monitor for occult blood in stool if symptoms suggest possible bleeding
   • Periodic complete blood counts to assess for anemia that might indicate GI blood loss

Considerations for Specific Conditions

For patients with myeloproliferative disorders (such as polycythemia vera or essential thrombocythemia):

• If intolerance to hydroxyurea develops due to GI effects, consider switching to interferon-alpha as second-line therapy 5
• The European LeukemiaNet defines intolerance to hydroxyurea as including "GI symptoms" among other unacceptable hydroxyurea-related nonhematologic toxicities 5

Conclusion

Gastrointestinal discomfort and bleeding are recognized adverse effects of hydroxyurea therapy. While most GI symptoms are mild and manageable, severe manifestations including ulceration and bleeding can occur. Prompt recognition and appropriate management, including discontinuation of the drug if necessary, are essential to prevent serious complications.