SIDE EFFECTS

See WARNINGS and Boxed Warning regarding the potential adverse effects on the fetus, the induction of malignant neoplasms, gallbladder disease, cardiovascular disease, elevated blood pressure, and hypercalcemia.

Skin irritation: In controlled clinical studies with Esclim (estradiol transdermal) , the most commonly reported adverse events were topical reactions of erythema and/or pruritus at the application site. In general these reactions caused patients little or no discomfort, and led to premature discontinuation of treatment in 0.9% (3/317) of patients in these trials. The rate of application site reactions, based on 8,135 applications of the 0.025, 0.05, and 0.1 Esclim (estradiol transdermal) systems in these trials was 6.1 per 100 applications (4.9, 5.4, 10.7 for the 3 Esclim (estradiol transdermal) doses respectively) compared to 6.2 in the placebo treated patients (2,014 applications).

In a placebo-controlled trial of Esclim (estradiol transdermal) 0.025, 0.05, and 0.1 conducted in 196 patients in the US, the adverse events reported by at least 5% of patients in 1 or more of the treatment groups are shown in Table 5.

Urogenital Adverse Events (See Precautions: Addition of a progestin): In the US placebo-controlled study, 72 patients were included who had intact uteri. As expected, after 12-13 weeks of continuous unopposed therapy, findings of endometrial hyperplasia (diagnosed either by endometrial biopsy and/or ultrasonography) were increased with increasing doses of estradiol (placebo: 0/18 patients; Esclim (estradiol transdermal) 0.025: 1/14 (7.1%); Esclim (estradiol transdermal) 0.05: 12/22 (54.5%); Esclim (estradiol transdermal) 0.1: 10/18 (55.6%). In the 86 patients who had not previously undergone a total hysterectomy, vaginal bleeding was also increased with increasing doses of estradiol [placebo: 2/21 patients (9.5%); Esclim (estradiol transdermal) 0.025: 6/19 (31.6%); Esclim (estradiol transdermal) 0.05: 14/25 (56.0%); Esclim (estradiol transdermal) 0.1: 12/21 (57.1%)].

In 2 long-term studies involving a total of 488 patients treated for a mean duration of 618 days and up to 3.5 years, the nature and incidence of adverse events did not change with prolonged duration of treatment.

The following additional adverse reactions have been reported with estrogen therapy:

1. Genitourinary System. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting; increase in size of uterine leiomyomata; vaginal candidiasis; change in amount of cervical secretion.

2. Breasts. Tenderness, enlargement.

3. Gastrointestinal. Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; gallbladder disease.

4. Skin. Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism.

5. Eyes. Steepening of corneal curvature: intolerance to contact lenses.

6. Central Nervous System. Headache, migraine, dizziness; mental depression; chorea.

7. Miscellaneous. Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; changes in libido.

Read the entire FDA prescribing information for Esclim (Estradiol Transdermal) »