From the Guidelines
Letrozole use is associated with significant side effects, including hot flashes, fatigue, arthritis, arthralgia, myalgia, and an increased risk of cardiovascular events and bone fractures, as evident from the MA.17R trial 1.
Common Side Effects
- Hot flashes: 38% of patients in the MA.17R trial experienced hot flashes 1
- Fatigue: 36% of patients in the MA.17R trial experienced fatigue 1
- Arthritis: 33% of patients in the MA.17R trial experienced arthritis 1
- Arthralgia: 53% of patients in the MA.17R trial experienced arthralgia 1
- Myalgia: 28% of patients in the MA.17R trial experienced myalgia 1
Serious Side Effects
- Cardiovascular events: a recent meta-analysis found an increased odds of cardiovascular events with prolonged AI treatment, including letrozole 1
- Bone fractures: the same meta-analysis found an increased odds of bone fractures with prolonged AI treatment, including letrozole 1
- Osteoporosis: letrozole use can lead to bone loss, increasing the risk of osteoporosis and fractures 1
Management of Side Effects
Regular monitoring by a healthcare provider is crucial to manage side effects appropriately and minimize the risk of serious complications. This includes monitoring for cardiovascular events, bone density, and managing symptoms such as hot flashes and joint pain. The benefits of letrozole in treating breast cancer must be weighed against the potential risks and side effects, and patients should be closely monitored and supported throughout treatment 1.
From the FDA Drug Label
Adverse Reactions Occurring at a Frequency of at Least 5% of Patients in Either Treatment Arm 1Includes peripheral edema, leg edema, dependent edema, edema 2Includes musculoskeletal pain, skeletal pain, back pain, arm pain, leg pain 3Includes rash, erythematous rash, maculopapular rash, psoriasiform rash, vesicular rash AdversePooledPooledMegestrol ReactionsLetrozoleLetrozoleAcetateAminoglutethimide 2.5 mg0. (N = 359) (N = 380) (N = 189) (N = 178) y as a Whole Chest Pain6373 Peripheral Edema 15583 Asthenia4545 Weight Increase2293 Cardiovascular Hypertension5756 Digestive System Nausea1315914 Vomiting7759 Constipation6797 Diarrhea6534 Pain-Abdominal6598 Anorexia5355 Dyspepsia3465 Infections/Infestations Viral Infection6563 Lab Abnormality Hypercholesterolemia3306 Musculoskeletal System Musculoskeletal 221223014 Arthralgia8883 Nervous System Headache91297 Somnolence3229 Dizziness3573 Respiratory System Dyspnea79165 Coughing6575 Skin and Appendages Hot Flushes6543 Rash 354312 Pruritus1253
The common side effects of letrozole include:
- Hot flushes (65.4%)
- Nausea (13.15%)
- Fatigue (45%)
- Headache (9.12%)
- Dizziness (3.57%)
- Vomiting (7.75%)
- Constipation (6.79%)
- Diarrhea (6.53%)
- Abdominal pain (6.59%)
- Anorexia (5.35%)
- Dyspepsia (3.46%)
- Arthralgia (8.83%)
- Musculoskeletal pain (22.12%)
- Rash (3.54%)
- Pruritus (1.25%) 2
From the Research
Letrozole Side Effects
- Letrozole is associated with significantly more osteoporotic fractures and greater bone mineral loss compared to other treatments such as tamoxifen 3
- The use of letrozole can lead to bone loss, which can be prevented or minimized with the use of bisphosphonates such as zoledronic acid 4, 5
- Common side effects of letrozole include hot flashes, osteoporosis, and an increased risk of fractures 6
- Letrozole can also cause apoptosis, necrosis, and fibrosis, leading to the death of cancer cells, but can also have adverse effects on the heart, kidney, liver, embryo, bone, and ovary 7
- Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on aminoglutethimide (46%) 6
Bone-Related Side Effects
- Letrozole can cause bone loss, which can be prevented or minimized with the use of bisphosphonates such as zoledronic acid 4, 5
- Zoledronic acid has been shown to increase bone mineral density (BMD) in postmenopausal women with osteoporosis or osteopenia who are taking letrozole 4, 5
- The use of zoledronic acid can prevent further bone loss in postmenopausal breast cancer patients with osteopenia and osteoporosis starting treatment with letrozole 5