The following serious adverse reactions are discussed elsewhere in the labeling:
- Cardiovascular Disorders [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Malignant Neoplasms [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
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.
Adverse reactions reported by ≥ 5 percent of subjects in controlled clinical studies of femhrt are shown in Table 1.
Table 1: Associated Adverse Reactions Reported by ≥ 5 Percent of Subjects by Body Systema
|BODY SYSTEM/Adverse Reaction||Placebo
N = 247
|Number (Percent) of Subjects|
N = 244
N = 258
|BODY AS A WHOLE||23 (12.8)||30 (16.9)||30 (15.7)|
|Edema - Generalized||10 (4.0)||12 (4.9)||11 (4.3)|
|Headache||12 (4.9)||14 (5.7)||16 (6.2)|
|DIGESTIVE SYSTEM||8 (4.4)||17 (9.6)||25 (13.1)|
|Abdominal Pain||3 (1.2)||13 (5.3)||14 (6.8)|
|UROGENITAL SYSTEM||20 (11.1)||34 (19.2)||45 (23.6)|
|Breast Pain||9 (3.6)||22 (9.0)||20 (7.8)|
|aThe total number of subjects for each body system may be less than the number of subjects with AEs in that body system because a subject may have had more than one AE per body system|
The following additional adverse reactions have been identified during post-approval use of femhrt. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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; uterine cancer; vaginal hemorrhage; ovarian cyst; irregular menstruation; metrorrhagia; menorrhagia; dysmenorrhea; uterine enlargement.
Tenderness, enlargement, breast pain, nipple pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer; breast disorder; breast mass; breast enlargement.
Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; thrombosis; chest pain; myocardial infarction; cerebrovascular accident (stroke); transient ischemic attack; hemiparesis; increase in blood pressure; irregular heart rate; palpitations; dyspnea.
Nausea, vomiting; cholestatic jaundice; pancreatitis, enlargement of hepatic hemangiomas; bloating, abdominal cramps; abdominal pain; increased incidence of gallbladder disease; cholecystitis; cholelithiasis.
Chloasma or melasma that may persist when drug is discontinued; generalized erythema; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; rash, pruritus.
Retinal vascular thrombosis; visual impairment; intolerance to contact lenses.
Central Nervous System (CNS)
Headache; migraine; dizziness; depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia; paresthesia; insomnia.
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps; back pain; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides; blood glucose abnormal; fatigue; myalgia; hypersensitivity.