Estrogel (Estradiol Topical) - Side Effects and Adverse Reactions

ADVERSE EVENTS

See BOXED WARNINGS, WARNINGS and PRECAUTIONS.

Because clinical trials are conducted under widely varying conditions, adverse event 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 event 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.

EstroGel 1.25 g was studied in 2 well-controlled 12-week clinical trials. Incidence of adverse events =5% for 1.25 g EstroGel and placebo is given below in Table 4.

TABLE 4 Incidence of Treatment-emergent Signs and Symptoms =5% By COSTART Body System and by Descending Frequency of Occurrence in the EstroGel Treatment Group for the Intent-to-Treat Safety Population in 2 Well-controlled Clinical Studies (Expressed as % of Treatment Group)

Body System/Treatment-emergent Signs and Symptoms	EstroGel 1.25 g day (n=168)	Placebo (n=73)
* Infection: upper respiratory infection, common cold, eye infection. † Pain: generalized and extremity aches/pains, cramps. ‡ Rash and pruritus: more than half of the EstroGel-treated patients who had pruritus reported itching at a body site other than the arms or reported generalized itching or itching skin. Similarly, most of the EstroGel-treated patients with rash had rash on 1 or more areas of the body in addition to the arms. § Endometrial disorder: proliferative endometrium, benign endometrial disorders. || Pap smear suspicious: atypical squamous cells of undetermined significance, inflammatory changes, epithelial cell abnormality.
BODY AS A WHOLE
Headache	20.2	17.8
Infection*	17.3	6.8
Pain†	7.1	11.0
Abdominal pain	7.7	1.4
Back pain	4.8	4.1
Flu syndrome	5.4	1.4
Asthenia	4.8	4.1
CARDIOVASCULAR SYSTEM
Palpitations	0.6	1.4
DIGESTIVE SYSTEM
Nausea	6.0	4.1
Flatulence	6.5	5.5
Diarrhea	4.2	0.0
METABOLIC and NUTRITIONAL SYSTEMS
Weight gain	2.4	0.0
NERVOUS SYSTEM
Nervousness	2.4	1.4
Depression	3.0	2.7
Anxiety	1.8	0.0
RESPIRATORY SYSTEM
Sinusitis	3.6	1.4
Rhinitis	2.4	6.8
SKIN AND APPENDAGES
Rash‡	7.1	5.5
Pruritus‡	4.8	2.7
Application-site reaction	0.6	0.0
UROGENITAL
Breast pain	12.5	9.6
Metrorrhagia	3.0	0.0
Endometrial disorder§	1.8	1.4
Vaginitis	8.9	4.1
Pap smear suspicious||	5.4	2.7
Vaginal hemorrhage	1.2	0.0

The following additional adverse events have been reported with estrogen and/or progestin therapy.

1. Genitourinary system: changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea; 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
2. Breasts: tenderness; enlargement; pain; nipple discharge; galactorrhea; fibrocystic breast changes; breast cancer
3. Cardiovascular: deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure
4. Gastrointestinal: nausea; bloating; diarrhea; dyspepsia; constipation; vomiting; abdominal cramps; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas
5. Skin: chloasma or melasma, which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus; rash
6. Eyes: retinal vascular thrombosis, intolerance to contact lenses
7. Central nervous system: headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia
8. Miscellaneous: increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ESTROGEL

Possible Estrogel side effects / adverse reactions in 49 year old female

Reported by a individual with unspecified qualification from United States on 2007-04-25

Patient: 49 year old female weighing 49.0 kg (107.8 pounds)

Reactions: Haemoptysis, Lung Neoplasm, Epistaxis

Suspect drug(s):
Estrogel
    Dosage: 1.25 grams at bedtime transcutaneous
    Indication: Hysterectomy
    Start date: 2007-03-08
    End date: 2007-03-19

Estrogel
    Dosage: 1.25 grams at bedtime transcutaneous
    Indication: Hysterectomy
    Start date: 2007-04-04

Other drugs received by patient: Remeron; Xanax; Aspirin