What is the management for a raloxifene (selective estrogen receptor modulator) overdose?

Management of Raloxifene Overdose

In cases of raloxifene overdose, supportive care is the recommended approach as there is no specific antidote available. 1

Clinical Presentation of Raloxifene Overdose

Raloxifene overdose has been reported very rarely in post-marketing surveillance (less than 0.01% of patients treated). Based on FDA documentation, the following symptoms may occur:

• Most common symptoms:

  • Leg cramps
  • Dizziness

• Additional symptoms reported in pediatric ingestions:

  • Ataxia
  • Vomiting
  • Rash
  • Diarrhea
  • Tremor
  • Flushing
  • Elevation in alkaline phosphatase 1

Management Protocol

1. Initial Assessment

   • Assess vital signs and stabilize if necessary
   • Evaluate for symptoms of overdose (leg cramps, dizziness, ataxia)
   • Check for signs of thromboembolic events (as raloxifene increases this risk at therapeutic doses)

2. Supportive Care

   • No specific antidote exists for raloxifene overdose 1
   • Provide symptomatic treatment for presenting complaints
   • Monitor for potential complications, particularly thromboembolic events

3. Laboratory Evaluation

   • Consider checking alkaline phosphatase levels (reported to be elevated in pediatric cases)
   • Monitor electrolytes and renal function
   • Consider coagulation studies if there are concerns about thromboembolic risk

4. Special Considerations

   • Use caution in patients with moderate to severe renal impairment
   • Use caution in patients with hepatic impairment
   • Elderly patients may not require dose adjustment based on age alone 1

Safety Profile

The FDA label notes that doses of 600 mg/day (10 times the standard therapeutic dose of 60 mg/day) have been safely tolerated in clinical studies. The highest reported overdose has been approximately 1.5 grams, with no fatalities reported from raloxifene overdose. 1

Animal studies have shown no mortality after single oral doses of:

• 5000 mg/kg in rats and mice (405-810 times the human dose based on surface area)
• 1000 mg/kg in monkeys (80 times the AUC in humans) 1

Monitoring and Follow-up

• Monitor patients for at least 24 hours if symptomatic
• Pay particular attention to patients with pre-existing risk factors for venous thromboembolism
• Consider longer observation in patients with renal or hepatic impairment as these conditions may affect raloxifene clearance

Pitfalls and Caveats

• Do not confuse raloxifene overdose management with that of tamoxifen (another SERM) as their side effect profiles differ
• Remember that raloxifene is primarily used in postmenopausal women for osteoporosis and breast cancer risk reduction, so accidental ingestion by children is rare but requires special attention
• Avoid medications that might increase the risk of thromboembolism in patients who have overdosed on raloxifene

The relatively benign clinical course of reported raloxifene overdoses suggests that most cases can be managed with supportive care alone, with particular attention to monitoring for the development of leg cramps, dizziness, and potential thromboembolic complications.