Short answer: In the label's extended adjuvant trial against placebo, the most common Femara side effects were flushing (49.7% vs 43.3%), weakness (33.6% vs 32.1%), increased sweating (24.2% vs 22.4%), joint pain (22% vs 18.1%) and headache (20.1% vs 19.7%). The label also warns about bone loss and fractures, higher cholesterol, and tiredness or dizziness. There is no boxed warning.
What Femara is approved for: Femara is an aromatase inhibitor approved for postmenopausal women with breast cancer: as adjuvant (after-surgery) treatment of hormone receptor-positive early breast cancer, as extended adjuvant treatment after 5 years of tamoxifen, and as first- or second-line treatment of hormone receptor-positive or unknown advanced breast cancer (section 1).
Source
FEMARA (letrozole) tablets, for oral use, prescribing information. Novartis. DailyMed, version published June 15, 2026. DailyMed setid 82b77d74-085f-45ac-a7dd-1f5c038bf406
No. The current Femara label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Femara.
| Adverse reaction | Femara Grade 1-4 (N = 2563) n (%) | Placebo Grade 1-4 (N = 2573) n (%) | Femara Grade 3-4 n (%) | Placebo Grade 3-4 n (%) |
|---|---|---|---|---|
| Any Adverse Reactions | 2232 (87.1) | 2174 (84.5) | 419 (16.3) | 389 (15.1) |
| Flushing | 1273 (49.7) | 1114 (43.3) | 3 (0.1) | 0 |
| Asthenia | 862 (33.6) | 826 (32.1) | 16 (0.6) | 7 (0.3) |
| Edema NOS | 471 (18.4) | 416 (16.2) | 4 (0.2) | 3 (0.1) |
| Arthralgia | 565 (22) | 465 (18.1) | 25 (1) | 20 (0.8) |
| Arthritis NOS | 173 (6.7) | 124 (4.8) | 10 (0.4) | 5 (0.2) |
| Myalgia | 171 (6.7) | 122 (4.7) | 8 (0.3) | 6 (0.2) |
| Back Pain | 129 (5) | 112 (4.4) | 8 (0.3) | 7 (0.3) |
| Headache | 516 (20.1) | 508 (19.7) | 18 (0.7) | 17 (0.7) |
| Dizziness | 363 (14.2) | 342 (13.3) | 9 (0.4) | 6 (0.2) |
| Sweating Increased | 619 (24.2) | 577 (22.4) | 1 (< 0.1) | 0 |
| Constipation | 290 (11.3) | 304 (11.8) | 6 (0.2) | 2 (< 0.1) |
| Nausea | 221 (8.6) | 212 (8.2) | 3 (0.1) | 10 (0.4) |
| Diarrhea NOS | 128 (5) | 143 (5.6) | 12 (0.5) | 8 (0.3) |
| Hypercholesterolemia | 401 (15.6) | 398 (15.5) | 2 (< 0.1) | 5 (0.2) |
| Vaginal Hemorrhage | 123 (4.8) | 171 (6.6) | 2 (< 0.1) | 5 (0.2) |
| Vulvovaginal Dryness | 137 (5.3) | 127 (4.9) | 0 | 0 |
| Insomnia | 149 (5.8) | 120 (4.7) | 2 (< 0.1) | 2 (< 0.1) |
| Dyspnea | 140 (5.5) | 137 (5.3) | 21 (0.8) | 18 (0.7) |
Extended adjuvant trial (MA-17): postmenopausal women with early breast cancer who had finished 5 years of tamoxifen, median 24 months of treatment. Shown are the individual reactions; body-system totals are left out. The label says hot flashes, arthralgia/arthritis and myalgia were the drug-related reactions significantly different from placebo.
| Adverse Reaction | Femara (N = 2448) n (%) | Tamoxifen (N = 2447) n (%) |
|---|---|---|
| Hypercholesterolemia | 1280 (52.3) | 700 (28.6) |
| Hot flashes | 819 (33.5) | 929 (38.0) |
| Arthralgia/arthritis | 621 (25.4) | 504 (20.6) |
| Bone fractures | 361 (14.7) | 280 (11.4) |
| Night sweats | 356 (14.5) | 426 (17.4) |
| Weight increase | 317 (12.9) | 378 (15.4) |
| Nausea | 284 (11.6) | 277 (11.3) |
| Fatigue (lethargy, malaise, asthenia) | 235 (9.6) | 250 (10.2) |
| Myalgia | 221 (9.0) | 212 (8.7) |
| Vaginal bleeding | 129 (5.3) | 320 (13.1) |
| Osteoporosis | 126 (5.1) | 67 (2.7) |
Adjuvant trial (BIG 1-98) comparing Femara with tamoxifen, not placebo. Shown are the most frequent rows, all grades. Bone fractures here are at any time after randomization (median 96 months follow-up).
Bone density: in a 2-year adjuvant study, lumbar spine bone density fell a median 4.1% on letrozole vs a 0.3% rise on tamoxifen. In the extended adjuvant study, hip bone density fell 3.8% vs 2.0% on placebo at 2 years.
Extended adjuvant trial at 62 months median follow-up: new fractures 13.3% on letrozole vs 7.8% on placebo, new osteoporosis 14.5% vs 7.8%, and cardiovascular disease 14.4% vs 9.8% at any time after randomization.
In the adjuvant trial, total cholesterol rose to 1.5 times the upper limit of normal or more in 8.4% on letrozole vs 3.9% on tamoxifen, and lipid-lowering medicine was needed by 29% vs 20%.
Advanced breast cancer, first line (Table 4, Femara vs tamoxifen): bone pain 22% vs 21%, hot flushes 19% vs 16%, back pain 18% vs 19%, shortness of breath 18% vs 17%, nausea 17% vs 17%, joint pain 16% vs 15%, fatigue 13% vs 13%.
Reported after approval: blurred vision, raised liver enzymes and hepatitis, anaphylaxis and allergic reactions, carpal tunnel syndrome, angioedema and severe skin reactions, tendon problems including tendon rupture and trigger finger, and miscarriage and birth defects when used in pregnancy.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Bone loss. Femara may lower bone mineral density, and the label says bone density monitoring should be considered. Fractures and osteoporosis were more frequent than on tamoxifen or placebo in the trials.
Cholesterol. Total cholesterol may rise, and the label says cholesterol monitoring should be considered. High cholesterol was reported in 52.3% on letrozole vs 28.6% on tamoxifen in the adjuvant trial.
Liver impairment. People with cirrhosis and severe liver impairment had about twice the exposure of healthy volunteers, so the dose is reduced for them.
Tiredness and dizziness. Fatigue, dizziness and sleepiness have been reported, so the label advises caution with driving or machinery until it is known how Femara affects a person.
Lab test changes. Moderate drops in lymphocyte counts were seen in some patients, about half of them temporary. Two patients developed low platelets, with an unclear link to Femara.
Harm to an unborn baby. Femara can cause fetal harm and is contraindicated in pregnancy. A pregnancy test is done before starting in women who could become pregnant, and effective contraception is used during treatment and for at least 3 weeks after the last dose.
Who should not use it. Pregnant women and people allergic to letrozole or any of the tablet's ingredients.
From the Patient Counseling Information (section 17); the label has no separate Patient Information leaflet that comes with Femara:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.