ELESTRIN

Product Type: HUMAN PRESCRIPTION DRUG

Route: TOPICAL

Dosage Form:

NDC: 0037-4801

Application: NDA021813

Effective: 20231215

1 INDICATIONS AND USAGE ELESTRIN is an estrogen indicated for the treatment of moderate to severe vasomotor symptoms due to menopause ( 1.1 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestin to reduce the risk of endometrial cancer. Generally, a woman without a uterus does not need to take a progestin in addition to her estrogen therapy. In some cases, however, hysterectomized women who have a history of endometriosis may need a progestin [see Warnings and Precautions (5.2) , (5.14) ] . Use estrogen-alone, or in combination with a progestin, at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary. ELESTRIN is applied onto the skin in a thin layer. The recommended area of application is the upper arm to shoulder (approximately 320 cm 2 ). Start therapy with daily administration of one pump actuation to deliver 0.87 grams of gel providing 0.52 mg estradiol to the upper arm. Dosage adjustment should be guided by the clinical response ( 2.1 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ELESTRIN is applied once daily to the upper arm for the treatment of moderate to severe vasomotor symptoms due to menopause using a metered-dose pump which delivers 0.87 grams of estradiol gel (0.52 mg estradiol) per actuation (1 pump). Start therapy with one pump per day (0.87 grams per day, which contains 0.52 mg of estradiol). Make dosage adjustments based on clinical response.

4 CONTRAINDICATIONS ELESTRIN is contraindicated in women with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2) ] . • Breast cancer or a history of breast cancer [see Warnings and precautions (5.2) ] . • Estrogen-dependent neoplasia [see Warnings and Precautions (5.2) ] . • Active DVT, PE, or history of these conditions [see Warnings and Precautions (5.1) ] . • Active arterial thromboembolic disease (for example, stroke and MI) or a history of these conditions [see warnings and Precautions (5.1) ] . • Known anaphylactic reaction, or angioedema, or hypersensitivity to ELESTRIN. • Hepatic impairment or disease. • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. • Undiagnosed abnormal genital bleeding ( 4 ) • Breast cancer or a history of breast cancer ( 4 , 5.2 ) • Estrogen-dependent neoplasia ( 4 , 5.2 ) • Active DVT, PE, or history of these conditions ( 4 , 5.1 ) • Active arterial thromboembolic disease (for example, stroke and MI) or a history of these conditions ( 4 , 5.1 ) • Known anaphylactic reaction or angioedema or hypersensitivity with ELESTRIN ( 4 ) • Hepatic impairment or disease ( 4 , 5.10 ) • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )

Not available.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Cardiovascular Disorders [see Boxed Warning , and Warnings and Precautions (5.1) ]. • Malignant Neoplasms [see Boxed Warning , and Warnings and Precautions (5.2) ]. The most common adverse reactions (≥ 5 percent) in any ELESTRIN treatment group are: breast tenderness, metrorrhagia, nasopharyngitis, and upper respiratory tract infections. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Meda at 1-877-999-8401 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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. ELESTRIN was studied in a placebo-controlled trial that included a total of 484 postmenopausal women. The adverse reactions that occurred at a rate greater than 5 percent in any of the treatment groups are summarized in Table 1. TABLE 1 - Incidence of Treatment-Emergent Adverse Reactions Occurring in ≥ 5 Percent of Women Body System / Signs and Symptoms Number (%) of Women Placebo (n = 137) ELESTRIN 0.87 g/day (n = 136) ELESTRIN 1.7 g/day (n = 142) Reproductive system & breast disorders Breast tenderness 5 (3.6) 9 (6.6) 11 (7.7) Metrorrhagia 3 (2.2) 6 (4.4) 13 (9.2) Respiratory, thoracic & mediastinal disorders Nasopharyngitis 10 (7.3) 14 (10.3) 12 (8.5) Upper respiratory tract infection 5 (3.6) 8 (5.9) 5 (3.5) 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ELESTRIN. 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. 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. 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 gallbladder disease; pancreatitis, enlargement of hepatic hemangiomas. Skin Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; 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; arthralgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.