What are the side effects of letrozole (Femara)?

Side Effects of Letrozole (Femara)

Letrozole commonly causes hot flashes, musculoskeletal symptoms (arthralgia, myalgia, bone pain), fatigue, and increased risk of osteoporosis and bone fractures, with these side effects affecting quality of life but rarely leading to serious complications when properly managed. 1, 2

Common Side Effects

Musculoskeletal Effects

• Arthralgia (joint pain): Affects up to 53% of patients 1, 2
• Myalgia (muscle pain): Occurs in approximately 28-36% of patients 1, 2
• Bone pain: Reported in 6-7% of patients 2
• Musculoskeletal stiffness: Affects about 5% of patients 2

Vasomotor Symptoms

• Hot flashes/flushes: Experienced by 38-54% of patients 1, 2
• Sweating: Reported in approximately 24% of patients 2

Bone Health Issues

• Osteoporosis: Develops in 11-21% of patients 1, 2
• Bone fractures: Occur in 8-14% of patients 1, 2
• Bone mineral density loss: Median decrease of 4.1% in lumbar spine after 24 months 2

Other Common Side Effects

• Fatigue: Affects 36-45% of patients 1, 2
• Headache: Occurs in 6-20% of patients 2
• Insomnia: Reported in 5-8% of patients 2
• Hypercholesterolemia: Affects 7-16% of patients 2
• Hypertension: Occurs in 7-8% of patients 2
• Depression: Reported in 6-7% of patients 2
• Nausea: Affects 6-9% of patients 2
• Dizziness: Occurs in 5-14% of patients 2

Comparison with Tamoxifen

Letrozole and tamoxifen have distinctly different side effect profiles:

• Letrozole is more commonly associated with:

  • Musculoskeletal symptoms
  • Osteoporosis
  • Increased bone fracture risk
  • Mild increases in cholesterol 1, 3

• Tamoxifen is more commonly associated with:

  • Increased risk of uterine cancer
  • Deep venous thrombosis
  • Endometrial effects 1, 3

Management of Side Effects

Bone Health

• Baseline bone mineral density assessment before starting therapy
• Regular monitoring during treatment
• Calcium and vitamin D supplementation
• Consider bisphosphonates for patients with osteoporosis or high fracture risk 1, 3

Musculoskeletal Symptoms

• Regular exercise and physical activity
• Anti-inflammatory medications for pain relief
• Physical therapy for persistent symptoms
• Consider switching to a different aromatase inhibitor if symptoms are severe and persistent 3

Vasomotor Symptoms

• Layered clothing
• Avoiding triggers (spicy foods, alcohol, caffeine)
• Maintaining cool environment
• Consider non-hormonal medications for severe symptoms (e.g., venlafaxine, gabapentin) 3

Cardiovascular Risk

• Regular monitoring of blood pressure
• Lipid profile assessment
• Lifestyle modifications (diet, exercise)
• Treatment of hypertension and hypercholesterolemia if present 1

Special Considerations

Extended Therapy

• Side effects may persist or worsen with extended therapy beyond 5 years
• Bone-related adverse events are more frequent in patients continuing letrozole for an additional 5 years 3
• The risk of osteoporotic fractures increases with longer duration of treatment 1

Intermittent vs. Continuous Therapy

• Intermittent letrozole administration may lead to greater improvement in hot flashes compared to continuous administration 1
• Consider intermittent scheduling for patients with severe vasomotor symptoms

Monitoring Recommendations

• Bone mineral density assessment at baseline and periodically during treatment
• Lipid profile monitoring
• Regular blood pressure checks
• Assessment of musculoskeletal symptoms
• Evaluation of vasomotor symptoms and their impact on quality of life 1, 3

Remember that while these side effects are common, they are generally manageable with appropriate interventions. The benefits of letrozole therapy in reducing breast cancer recurrence must be weighed against these side effects for each individual patient.