From the Guidelines
Femara (letrozole) can cause several adverse effects, including hot flashes, joint or muscle pain, fatigue, headache, and increased sweating, with more concerning effects being bone loss and increased risk of osteoporosis, as well as cardiovascular effects such as elevated cholesterol levels and hypertension, as reported in the most recent study 1.
Common Adverse Effects
- Hot flashes
- Joint or muscle pain
- Fatigue
- Headache
- Increased sweating Some patients may also experience nausea, dizziness, and insomnia.
More Concerning Adverse Effects
- Bone loss and increased risk of osteoporosis, with a trend toward higher osteoporotic fractures with use of extended AI therapy, as seen in the study 1
- Cardiovascular effects, including elevated cholesterol levels, hypertension, and rarely, heart attacks or strokes, with a recent meta-analysis calculating the odds of cardiovascular events between patients who were randomly assigned to prolonged treatment with AIs and those randomly assigned to placebo or no treatment in phase III RCTs, showing an increased odds of cardiovascular events (odds ratio [OR], 1.18; 95% CI, 1.00 to 1.40; P = .05; number needed to harm [NNH], 122) 1
Less Common but Serious Adverse Effects
- Liver function abnormalities
- Severe skin reactions
- Vision disturbances These effects occur because letrozole is an aromatase inhibitor that blocks the production of estrogen, which is necessary for cancer treatment but also plays important roles in maintaining bone density, cardiovascular health, and other bodily functions.
Recommendation
Patients should report persistent or severe side effects to their healthcare provider, who may recommend supportive treatments or medication adjustments, as the benefits of letrozole in the treatment of hormone receptor-positive breast cancer outweigh the risks, as shown in the study 1.
From the FDA Drug Label
Table 2 describes adverse reactions (Grades 1 to 4 and Grades 3 to 4) irrespective of relationship to study treatment in the adjuvant study (safety population)
Adverse ReactionsLetrozole N = 2049 n (%)Anastrozole N = 2062 n (%) Grade 3/4 n (%)All Grades n (%)Grade 3/4 n (%)All Grades n (%) ... Arthralgia80 (3.9)987 (48.2)69 (3.3)987 (47. 9) Hot flush17 (0.8)666 (32.5)9 (0.4)666 (32.3) Fatigue8 (0.4)345 (16.8)10 (0.5)343 (16.6) ...
Table 3: Adverse Reactions Occurring in at least 5% of Patients in either Treatment Arm Number (%) of Patients with Grade 1 to 4 Adverse ReactionsNumber (%) of Patients with Grade 3 to 4 Adverse Reactions LetrozolePlaceboLetrozolePlacebo N = 2563N = 2573N = 2563N = 2573 Any Adverse Reactions2232 (87.1)2174 (84.5)419 (16.3)389 (15.1) ...
Table 4: Adverse Reactions Occurring in at least 5% of Patients in either Treatment Arm AdverseLetrozoleTamoxifen Reactions2. (N = 455) (N = 455) 84 Gastrointestinal Disorders Nausea1717 Constipation1011 Diarrhea84 Vomiting78 ...
Table 5: Adverse Reactions Occurring at a Frequency of at Least 5% of Patients in Either Treatment Arm AdversePooledPooledMegestrol ReactionsLetrozoleLetrozoleAcetateAminoglutethimide 2.5 mg0. (N = 359) (N = 380) (N = 189) (N = 178) y as a Whole Chest Pain6373 Peripheral Edema 15583 Asthenia4545 ...
The adverse effects of Femara (letrozole) include:
- Arthralgia (48.2% of patients)
- Hot flushes (32.5% of patients)
- Fatigue (16.8% of patients)
- Nausea (17% of patients)
- Constipation (10% of patients)
- Diarrhea (8% of patients)
- Vomiting (7% of patients)
- Headache (9% of patients)
- Dizziness (4% of patients)
- Osteoporosis (10.9% of patients)
- Myalgia (11.4% of patients)
- Back pain (10.3% of patients)
- Pain in extremity (8.2% of patients)
- Lymphoedema (7.8% of patients)
- Insomnia (7.8% of patients)
- Hypercholesterolaemia (7.6% of patients)
- Hypertension (7.6% of patients)
- Depression (7.2% of patients)
- Bone pain (6.7% of patients)
- Nausea (6.7% of patients)
- Headache (6.3% of patients)
- Alopecia (6.2% of patients)
- Musculoskeletal pain (6% of patients)
- Radiation skin injury (5.9% of patients)
- Dyspnoea (5.8% of patients)
- Cough (5.8% of patients)
- Musculoskeletal stiffness (5% of patients)
- Dizziness (4.6% of patients)
- Fall (less than 5% of patients)
- Vertigo (less than 5% of patients)
- Hyperbilirubinemia (less than 5% of patients)
- Jaundice (less than 5% of patients)
- Chest pain (less than 5% of patients)
From the Research
Adverse Effects of Femara (Letrozole)
The adverse effects of Femara (letrozole) are well-documented in various studies. Some of the common adverse effects include:
- Hot flushes 3, 4
- Nausea 3
- Hair thinning 3
- Arthralgia (joint pain) 3
- Myalgia (muscle pain) 3
- Arthritis 3
- Osteoporosis due to estrogen deficiency 5
Cardiovascular Safety Profile
The cardiovascular safety profile of letrozole has been compared with tamoxifen in several studies. The results suggest that:
- Letrozole may be associated with a significantly greater incidence of cardiovascular events and a numerical increase of cerebrovascular and cardiac deaths compared with tamoxifen 6
- However, no increase in cardiovascular events with letrozole was reported in another study 6
- Letrozole is associated with a reduced incidence of thrombosis compared with tamoxifen 5
Other Adverse Effects
Other adverse effects of letrozole include: