Is danazol indicated for gastrointestinal (GI) angiodysplasia?

Danazol for GI Angiodysplasia

Danazol is not indicated as a first-line treatment for gastrointestinal angiodysplasia, but may be considered in specific cases of refractory bleeding, particularly in patients with underlying von Willebrand disease.

Current Treatment Approach for GI Angiodysplasia

First-Line Treatments

• Endoscopic therapy: Argon plasma coagulation is the preferred first-line treatment, resolving bleeding in approximately 85% of patients with colonic angiodysplasia 1
• Angiography with embolization: Suitable for hemodynamically unstable patients with active bleeding, patients with unknown active bleeding source, and poor surgical candidates 2

Pharmacological Options for Refractory Cases

1. Somatostatin analogues:

   • Octreotide and lanreotide have shown significant efficacy in refractory cases
   • Clinical response rates of 76% (95% CI 64-85%) with octreotide 3
   • Lanreotide demonstrates complete response in 18.5% of patients and 50% reduction in healthcare resource consumption in about 60% of patients 4

2. Danazol:

   • Limited evidence for use in general angiodysplasia cases
   • Most evidence supports its use specifically in patients with von Willebrand disease (VWD) who have concurrent GI angiodysplasia with refractory bleeding 5

Danazol in Specific Populations

Von Willebrand Disease with GI Angiodysplasia

• Danazol has shown efficacy in reducing GI bleeding and packed red blood cell transfusion requirements in patients with VWD and refractory GI bleeding from angiodysplasia 5
• Benefits may be variable and possibly transient
• Should be considered when conventional management (including von Willebrand factor concentrate replacement and endoscopic ablation) fails to control bleeding

Important Monitoring and Side Effects

• Regular liver function tests should be performed at least monthly 6
• Common side effects include:
  • Elevated liver function tests (16.5% of patients)
  • Weight gain (8.4%)
  • Amenorrhea in female patients (10.6%)
  • Mood changes 6
• Severe liver toxicity has been reported, particularly in patients with underlying liver conditions 5

Dosing Considerations

• Typical dosage ranges from 200-800 mg daily for adults 6
• For hereditary conditions requiring danazol, the effective dosage is 200 mg 2-4 times daily 6
• Doses should be adjusted to the lowest possible amount consistent with clinical response 7

Clinical Decision Algorithm for GI Angiodysplasia

1. First attempt endoscopic therapy (argon plasma coagulation) for accessible lesions
2. Consider angiography with embolization for hemodynamically unstable patients or inaccessible lesions
3. For refractory bleeding:
   • First choice: Somatostatin analogues (octreotide or lanreotide)
   • Consider danazol only if:
     • Patient has underlying von Willebrand disease
     • Other treatments have failed
     • Patient can tolerate potential side effects and undergo regular monitoring

Important Caveats

• Danazol should not be a first-line therapy for patients who have both angiodysplasia and breast cancer due to conflicting data on androgen effects 7
• Careful monitoring for liver toxicity is essential, with monthly liver function tests 6, 5
• The primary aim of danazol treatment in refractory cases is to reduce transfusion dependence rather than achieve complete resolution 5