See BOXED WARNINGS, WARNINGS and PRECAUTIONS.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Incidence of adverse events > 2% of each treatment group is given in Table 5.
Table 5: Incidence of Adverse Events > 2% for Alora (estradiol transdermal system) and Placebo Systems (data are expressed as N and (%) of treatment group)
| Body System Preferred Term | Placeboa (N=87) |
Alora (estradiol transdermal system) a 0.025 mg/day (N=89) |
Alora (estradiol transdermal system) a 0.05 mg/day (N=90) |
Alora (estradiol transdermal system) a 0.075 mg/day (N=89) |
Alora (estradiol transdermal system) b 0.1 mg/day (N=174) |
| Body As A Whole | |||||
| Accidental Injury | 4 (4.6) | 6 (6.7) | 8 (8.9) | 4 (4.5) | 9 (5.2) |
| Allergic Reaction | 2 (2.3) | 4 (4.5) | 4 (4.4) | 2 (2.2) | 1 (0.6) |
| Asthenia | 4 (4.6) | 7 (7.9) | 4 (4.4) | 0 (0) | 4 (2.3) |
| Cyst | 3 (3.4) | 0 (0) | 6 (6.7) | 3 (3.4) | 0 (0) |
| Flu Syndrome | 9 (10.3) | 8 (9) | 12 (13.3) | 9 (10.1) | 6 (3.4) |
| Headache | 11 (12.6) | 10 (11.2) | 8 (8.9) | 5 (5.6) | 37 (21.3) |
| Infection | 2 (2.3) | 2 (2.2) | 3 (3.3) | 3 (3.4) | 2 (1.1) |
| Infection Fungal | 1 (1.1) | 3 (3.4) | 9 (10) | 4 (4.5) | 0 (0) |
| Pain | 11 (12.6) | 9 (10.1) | 5 (5.6) | 6 (6.7) | 16 (9.2) |
| Pain Abdominal | 4 (4.6) | 7 (7.9) | 5 (5.6) | 1 (1.1) | 5 (2.9) |
| Pain Back | 5 (5.7) | 5 (5.6) | 3 (3.3) | 7 (7.9) | 11 (6.3) |
| Pain Chest | 4 (4.6) | 4 (4.5) | 2 (2.2) | 1 (1.1) | 2 (1.1) |
| Cardiovascular | |||||
| Hypertension | 3 (3.4) | 3 (3.4) | 3 (3.3) | 6 (6.7) | 0 (0) |
| Migraine | 2 (2.3) | 6 (6.7) | 2 (2.2) | 0 (0) | 2 (1.1) |
| Vasodilation | 13 (14.9) | 6 (6.7) | 2 (2.2) | 1 (1.1) | 0 (0) |
| Digestive | |||||
| Constipation | 4 (4.6) | 3 (3.4) | 6 (6.7) | 1 (1.1) | 3 (1.7) |
| Diarrhea | 2 (2.3) | 1 (1.1) | 3 (3.3) | 2 (2.2) | 5 (2.9) |
| Dyspepsia | 1 (1.1) | 8 (9) | 4 (4.4) | 3 (3.4) | 2 (1.1) |
| Flatulence | 5 (5.7) | 1 (1.1) | 2 (2.2) | 3 (3.4) | 8 (4.6) |
| Gastroenteritis | 2 (2.3) | 3 (3.4) | 4 (4.4) | 3 (3.4) | 0 (0) |
| Nausea | 3 (3.4) | 6 (6.7) | 5 (5.6) | 3 (3.4) | 7 (4) |
| Metabolic And Nutritional | |||||
| Edema Peripheral | 4 (4.6) | 3 (3.4) | 4 (4.4) | 3 (3.4) | 3 (1.7) |
| Weight Increased | 4 (4.6) | 3 (3.4) | 2 (2.2) | 4 (4.5) | 1 (0.6) |
| Musculoskeletal | |||||
| Arthralgia | 12 (13.8) | 5 (5.6) | 10 (11.1) | 11 (12.4) | 2 (1.1) |
| Bone Fracture Spontaneous | 7 (8) | 1 (1.1) | 3 (3.3) | 0 (0) | 0 (0) |
| Joint Disorder | 2 (2.3) | 4 (4.5) | 4 (4.4) | 1 (1.1) | 0 (0) |
| Myalgia | 4 (4.6) | 3 (3.4) | 2 (2.2) | 5 (5.6) | 3 (1.7) |
| Nervous | |||||
| Anxiety | 3 (3.4) | 0 (0) | 9 (10) | 2 (2.2) | 3 (1.7) |
| Depression | 8 (9.2) | 1 (1.1) | 3 (3.3) | 1 (1.1) | 6 (3.4) |
| Dizziness | 0 (0) | 1 (1.1) | 7 (7.8) | 4 (4.5) | 1 (0.6) |
| Hypesthesia | 2 (2.3) | 3 (3.4) | 3 (3.3) | 0 (0) | 0 (0) |
| Insomnia | 7 (8) | 4 (4.5) | 2 (2.2) | 1 (1.1) | 8 (4.6) |
| Respiratory | |||||
| Asthma | 1 (1.1) | 3 (3.4) | 3 (3.3) | 1 (1.1) | 2 (1.1) |
| Bronchitis | 6 (6.9) | 7 (7.9) | 4 (4.4) | 4 (4.5) | 6 (3.4) |
| Cough Increased | 2 (2.3) | 1 (1.1) | 4 (4.4) | 1 (1.1) | 6 (3.4) |
| Infection Respiratory | 23 (26.4) | 22 (24.7) | 22 (24.4) | 19 (21.3) | 28 (16.1) |
| Pharyngitis | 1 (1.1) | 4 (4.5) | 2 (2.2) | 2 (2.2) | 4 (2.3) |
| Pneumonia | 4 (4.6) | 4 (4.5) | 4 (4.4) | 1 (1.1) | 1 (0.6) |
| Sinusitis | 16 (18.4) | 9 (10.1) | 11 (12.2) | 6 (6.7) | 13 (7.5) |
| Skin | |||||
| Application Site Reaction | 51 (58.6) | 47 (52.8) | 51 (56.7) | 49 (55.1) | 10 (5.7) |
| Hirsutism | 0 (0) | 2 (2.2) | 2 (2.2) | 4 (4.5) | 1 (0.6) |
| Pruritus | 4 (4.6) | 2 (2.2) | 1 (1.1) | 6 (6.7) | 9 (5.2) |
| Rash | 5 (5.7) | 6 (6.7) | 8 (8.9) | 4 (4.5) | 5 (2.9) |
| Special Senses | |||||
| Conjunctivitis | 2 (2.3) | 2 (2.2) | 3 (3.3) | 2 (2.2) | 0 (0) |
| Otitis Media | 2 (2.3) | 3 (3.4) | 2 (2.2) | 1 (1.1) | 0 (0) |
| Urogenital | |||||
| Breast Enlargement | 3 (3.4) | 1 (1.1) | 2 (2.2) | 6 (6.7) | 4 (2.3) |
| Infection Urinary Tract | 2 (2.3) | 5 (5.6) | 4 (4.4) | 2 (2.2) | 3 (1.7) |
| Leukorrhea | 1 (1.1) | 3 (3.4) | 2 (2.2) | 4 (4.5) | 3 (1.7) |
| Neoplasm Breast | 6 (6.9) | 3 (3.4) | 5 (5.6) | 1 (1.1) | 3 (1.7) |
| Pain Breast | 7 (8) | 13 (14.6) | 16 (17.8) | 31 (34.8) | 12 (6.9) |
| Vaginitis | 6 (6.9) | 0 (0) | 3 (3.3) | 0 (0) | 14 (8) |
| Vaginal Bleedingc | 4 (12.9) | NA | 6 (8.7) | NA | 29 (33.3) |
| a - Adverse events for the three lower Alora (estradiol transdermal system) doses and placebo were obtained from the two-year prevention of osteoporosis study b - Adverse events for the highest Alora (estradiol transdermal system) doses were obtained from two 12-week studies of the treatment of menopausal symptoms c - Data reported for women with partially or fully intact uteri in the menopausal symptom study only (N=31 for Placebo; N=69 for Alora (estradiol transdermal system) 0.05 mg/day and N=87 for Alora (estradiol transdermal system) 0.1 mg/day) NA – data not available |
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The following additional adverse reactions have been reported with estrogens and/or progestin therapy:
- Genitourinary system. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.
- Breasts. Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
- Cardiovascular. Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.
- Gastrointestinal. Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gall bladder disease; pancreatitis; enlargement of hepatic hemangiomas.
- Skin. Chloasma or melasma, which may persist when drug is discontinued; erythema multiform; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus; rash.
- Eyes.Retinal vascular thrombosis; intolerance to contact lenses.
- Central nervous system.Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.
- Miscellaneous.Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; anaphylactoid/anaphylactic reactions including urticaria and angioedema; hypocalcemia; exacerbation of asthma; increased triglycerides.