Usual Adult Dose for Postmenopausal Symptoms

Apply one patch (estradiol 0.045 mg per day/levonorgestrel 0.015 mg per day) to skin on lower abdomen or upper quadrant of buttock once a week

• For women not currently receiving continuous estrogen-alone or estrogen plus progestin therapy: May initiate therapy at any time
• For women currently receiving continuous estrogen-alone or estrogen plus progestin therapy: Complete cycle of current therapy before switching to this therapy; if withdrawal bleeding occurs at completion of cycle, the first day of bleeding would be an appropriate time to start this medication

• Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and individual risks.
• For treatment of moderate to severe vasomotor symptoms due to menopause, attempts to discontinue therapy should be made at 3 to 6 months intervals.
• When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered.

• Treatment of moderate to severe vasomotor symptoms due to menopause
• Prevention of postmenopausal osteoporosis

Usual Adult Dose for Prevention of Osteoporosis

Apply one patch (estradiol 0.045 mg per day/levonorgestrel 0.015 mg per day) to skin on lower abdomen or upper quadrant of buttock once a week

• For women not currently receiving continuous estrogen-alone or estrogen plus progestin therapy: May initiate therapy at any time
• For women currently receiving continuous estrogen-alone or estrogen plus progestin therapy: Complete cycle of current therapy before switching to this therapy; if withdrawal bleeding occurs at completion of cycle, the first day of bleeding would be an appropriate time to start this medication

• Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and individual risks.
• For treatment of moderate to severe vasomotor symptoms due to menopause, attempts to discontinue therapy should be made at 3 to 6 months intervals.
• When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered.

• Treatment of moderate to severe vasomotor symptoms due to menopause
• Prevention of postmenopausal osteoporosis

Renal Dose Adjustments

Use caution; no dose adjustments recommended

Liver Dose Adjustments

Known liver impairment or disease: Contraindicated

• For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, therapy should be discontinued if cholestatic jaundice recurs

Precautions

US BOXED WARNINGS: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER, AND PROBABLE DEMENTIA

• Cardiovascular Disorders: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease: The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years old) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) compared to placebo.
• Cardiovascular Disorders: Estrogen alone therapy should not be used for prevention of cardiovascular disease. The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years old) taking daily conjugated estrogens (0.625 mg) for 7.1 years, relative to placebo.
• Probable Dementia: Estrogen plus progestin therapy should not be used for the prevention of dementia: The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increase risk of developing probable dementia in postmenopausal women over 65 years old during 4 years of treatment with daily conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) compared to placebo; it is unknown if this applies to younger postmenopausal women.
• Probable Dementia: The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily conjugated estrones (0.625 mg) relative to placebo.
• Breast Cancer: The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
• Endometrial Cancer: Endometrial cancer risk is increased in a woman with a uterus using unopposed estrogens (estrogen-alone therapy). Adding a progestin to estrogen therapy reduces the risk of endometrial hyperplasia, which may be an endometrial cancer precursor. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

• Lacking comparable data, assume the risk is similar for other doses of conjugated estrogens and other forms of estrogen.
• Estrogens, with or without progestins, should be prescribed at the lowest effective dose for the shortest duration consistent with treatment goals and risks.

• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer
• Known or suspected estrogen dependent neoplasia
• Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history thereof
• Active or history of arterial thromboembolic disease (e.g. stroke or myocardial infarction)
• Know anaphylactic reaction or angioedema to active substances or excipients
• Known liver disease or impairment
• Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
• Known or suspected pregnancy

Dialysis

Hemodialysis: Use with caution; patients with ESRD receiving maintenance hemodialysis have higher total serum estradiol levels which may be excessive
Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• For transdermal use only
• Apply 1 patch to smooth, clean, dry area of skin on lower abdomen or upper quadrant of the buttock once every 7 days; ; remove old patch as new patch is applied
• Rotate application sites allowing at least 1-week between applications to the same site
• Apply immediately after opening pouch
• Press patch firmly against skin, holding for at least 10 seconds; if patch lifts apply pressure to maintain adhesion.
• Do not apply on or near the breasts.
• Avoid applying patch to the waistline and areas where sitting may dislodge patch; the application site should not be oily, damaged, or irritated
• If patch falls off, the same patch may be reapplied to another area of the lower abdomen or if patch cannot be reapplied, a new patch may be applied; only 1 system should be worn at any one time
• The effects of swimming, bathing, or using a sauna have not been studied; these activities may decrease patch adhesion and drug delivery.
• Remove patch carefully and slowly to avoid skin irritation.
• If adhesive remains on skin after removal, allow area to dry for 15 minutes, then gently rub area with an oil-based cream or lotion to remove adhesive residue.
• Used patches still contain active drug; to discard, fold sticky side together and place in trash away from pets and children; do not flush in toilet; if available, use a take-back program

• Do not store unpouched; apply immediately upon removal from pouch

• Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
• A careful appraisal of the risks and benefits should be undertaken at least annually; HRT should be continued only as long as the benefit outweighs the risks.

• A complete personal and family medical history should be performed prior to therapy
• Breast examinations including appropriate imaging tools (e.g. mammography) should performed in accordance with accepted screening practices and clinical needs of the patient
• Monitor thyroid function in women on thyroid replacement therapy

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Patients should be instructed to report any abnormal vaginal bleeding to their healthcare provider promptly.
• Patients should understand that serious adverse reactions are possible including cardiovascular disorders, malignant neoplasms, and dementia.