What are the side effects of Exemestane (an aromatase inhibitor)?

Side Effects of Exemestane

Exemestane commonly causes endocrine-related side effects including hot flashes, fatigue, sweating, and insomnia, as well as musculoskeletal symptoms, joint pain, and bone mineral density loss in postmenopausal women with breast cancer. 1

Common Side Effects

Exemestane, an irreversible steroidal aromatase inhibitor, has a specific side effect profile that patients and clinicians should be aware of:

Endocrine-Related Side Effects

• Hot flashes (13% of patients)
• Fatigue (8%)
• Increased sweating (4-6%)
• Insomnia 1, 2

Musculoskeletal Effects

• Joint and muscle pain
• Arthralgia
• Bone mineral density loss - statistically significant reduction in bone mineral density and cortical thickness at multiple sites including distal tibia, distal radius, lumbar spine, total hip, and femoral neck 1
• Increased risk of osteoporosis and fractures 2

Gastrointestinal Effects

• Nausea (9%)
• Diarrhea
• Vomiting (7%)
• Abdominal pain (6%)
• Increased appetite (3%) 2

Constitutional Symptoms

• Fatigue (22%)
• Pain (13%)
• Influenza-like symptoms (6%)
• Edema (7%) 2

Serious Side Effects

While exemestane is generally well-tolerated, some serious adverse events have been reported:

• No statistically significant differences in cardiovascular events compared to placebo 1
• No significant increase in skeletal fractures in clinical trials, though bone loss is a concern 1
• No significant increase in other cancers or treatment-related deaths 1
• Rare post-marketing reports include hypersensitivity reactions, hepatitis, and tendon disorders 2

Impact on Quality of Life

The MAP.3 trial demonstrated:

• Minimal overall differences in quality-of-life outcomes between exemestane and placebo groups
• Statistically significant increase in vasomotor symptoms, bodily pain, and sexual problems in women taking exemestane 1

Monitoring and Management

Bone Health

• Women receiving exemestane should undergo bone monitoring
• Adequate vitamin D and calcium supplementation is recommended
• The potential for bone loss should be discussed when considering exemestane therapy 1

Laboratory Monitoring

• Vitamin D level should be checked before starting treatment 2
• Monitor for signs of hepatic dysfunction (rare but reported) 2

Special Considerations

Contraindications

• Exemestane should not be used in premenopausal women or those with functioning ovaries 2
• Not recommended during pregnancy or breastfeeding 2

Drug Interactions

• Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) may significantly decrease exemestane exposure and require dose modification 2

Clinical Context

Exemestane is effective in reducing the risk of invasive breast cancer in postmenopausal women at increased risk, with a reduction of up to 73% in ER-positive invasive breast cancer 1. The side effect profile, while significant, is generally manageable and most adverse events are mild to moderate in severity 3, 4.

When discussing exemestane with patients, it's important to balance the significant clinical benefits against the potential side effects, particularly emphasizing bone health monitoring and management of endocrine-related symptoms that may affect quality of life.