The following list presents adverse reactions from clinical trials, post-marketing studies or spontaneous reports. Unless specified, the frequency categories were calculated from the number of adverse events reported in a large phase III study conducted in 9,366 postmenopausal women with operable breast cancer given adjuvant treatment for five years (the Anastrozole, Tamoxifen, Alone or in Combination [ATAC] study).
Adverse reactions listed below are classified according to frequency and System Organ Class (SOC). Frequency groupings are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000).
The most frequently reported adverse reactions were headache, hot flushes, nausea, rash, arthralgia, joint stiffness, arthritis, and asthenia.
Metabolism and nutrition disorders:
Common: Anorexia, hypercholesterolaemia.
Uncommon: Hypercalcaemia (with or without an increase in parathyroid hormone).
Nervous system disorders:
Very common: Headache.
Common: Somnolence, Carpal Tunnel Syndrome*
Very common: Hot flushes.
Very common: Nausea.
Common: Diarrhoea, vomiting.
Common: Increases in alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase.
Uncommon: Increases in gamma-GT and bilirubin, hepatitis.
Skin and subcutaneous tissue disorders:
Very common: Rash.
Common: Hair thinning (Alopecia).
Rare: Erythema multiforme, anaphylactoid reaction. Cutaneaous vasculitis (including some reports of Henoch-Schönlein purpura)**.
Very rare: Stevens-Johnson syndrome, angioedema.
Musculoskeletal and connective tissue disorders:
Very common: Arthralgia/joint stiffness, arthritis, osteoporosis.
Common: Bone pain, myalgia.
Uncommon: Trigger finger.
Reproductive system and breast disorders:
Common: Vaginal dryness, vaginal bleeding***.
General disorders and administration site conditions:
Very common: Asthenia.
*Events of Carpal Tunnel Syndrome have been reported in patients receiving anastrozole treatment in clinical trials in greater numbers than those receiving treatment with tamoxifen. However, the majority of these events occurred in patients with identifiable risk factors for the development of the condition.
**Since cutaneous vasculitis and Henoch-Schonlein purpura was not observed in ATAC, the frequency category for these events can be considered as 'Rare' (≥ 0.01% and < 0.1%) based on the worst value of the point estimate.
***Vaginal bleeding has been reported commonly, mainly in patients with advanced breast cancer during the first few weeks after changing from existing hormonal therapy to treatment with anastrozole. If bleeding persists, further evaluation should be considered.
The table presents the frequency of pre-specified adverse events in the ATAC study after a median follow-up of 68 months, irrespective of causality, reported in patients receiving trial therapy and up to 14 days after cessation of trial therapy. (See Table.)
Click on icon to see table/diagram/image
Fracture rates of 22 per 1,000 patient-years and 15 per 1,000 patient-years were observed for the anastrozole and tamoxifen groups, respectively, after a median follow-up of 68 months. The observed fracture rate for anastrozole is similar to the range reported in age-matched postmenopausal populations. The incidence of osteoporosis was 10.5% in patients treated with anastrozole and 7.3% in patients treated with tamoxifen.
It has not been determined whether the rates of fracture and osteoporosis seen in ATAC in patients on anastrozole treatment reflect a protective effect of tamoxifen, a specific effect of anastrozole, or both.