ESTRADOT

What it is

Estradot is a matrix transdermal drug delivery system (patch) containing estradiol. The medicine is available in five strengths: Estradot 25 with a nominal in vivo release rate of 25 micrograms estradiol per day, Estradot 37.5 with a release rate of 37.5 micrograms per day, Estradot 50 with a release rate of 50 micrograms per day, Estradot 75 with a release rate of 75 micrograms per day, and Estradot 100 with a release rate of 100 micrograms per day.

Approved indications

— Short term treatment of symptoms of estrogen deficiency due to the menopause, whether natural or surgically induced.

Dosing overview

Treatment is usually initiated with an Estradot 50 patch. Depending on the clinical response the dose should then be adjusted to the woman's individual needs. If, after three months, there is an insufficient response in the form of alleviated symptoms, the dose should be increased. If symptoms of overdose arise the dose should be decreased. Maintenance therapy must always be at the lowest effective dose. Estradot is administered as continuous therapy (uninterrupted application twice weekly). Estradot should be replaced twice weekly (i.e. every 3 to 4 days). The adhesive side of Estradot should be placed on a clean, dry area of the abdomen. The site of application must be rotated, with an interval of at least 1 week allowed between applications to a particular site.

Key safety warnings

Estrogens with or without progestogens should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative study reported increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 6.8 years of treatment with conjugated estrogens relative to placebo. The WHI study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with conjugated estrogens combined with medroxyprogesterone acetate relative to placebo. The Women's Health Initiative Memory Study reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 to 5.2 years of treatment with conjugated estrogens, with or without medroxyprogesterone acetate, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. Because of these risks, estrogens with or without progestogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users with an intact uterus is about 2- to 12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. The use of estrogens and progestogens by postmenopausal women has been reported to increase the risk of breast cancer. After a mean follow-up of 5.6 years, the WHI trial reported an increased risk of breast cancer in women who took estrogen plus progestogen. Cases of anaphylactic/anaphylactoid reactions, which developed anytime during the course of estradiol treatment and required emergency medical management, have been reported in the post marketing setting. Involvement of skin (urticaria, pruritus, swelling of the face, throat, lips, tongue, skin and periorbial oedema) and either respiratory tract (respiratory compromise) or gastrointestinal tract (abdominal pain, vomiting) has been noted. Patients who develop angioedema after treatment with estradiol should not receive Estradot again. A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Contraindications

Estradot is contraindicated in: known, past or suspected carcinoma of the breast; known or suspected carcinoma of the endometrium or other estrogen-dependent neoplasia; undiagnosed abnormal vaginal bleeding; severe hepatic impairment; active venous thromboembolism (including deep venous thrombosis and pulmonary embolism), known thrombophilic or thromboembolic disorders, or arterial thromboembolic disease; porphyria; known or suspected pregnancy; breast-feeding; non-hysterectomised women unless on concomitant progestogen therapy; and known hypersensitivity to estrogens or any other component of the patch.

PBS listing

Estradot transdermal patches are listed on the PBS in five strengths (390 micrograms, 585 micrograms, 780 micrograms, 1.17 mg, and 1.56 mg) with unrestricted access. The ex-manufacturer prices range from A$15.50 to A$16.85 per pack of 8 patches.

Regulatory history

Estradot was first registered on the Australian Register of Therapeutic Goods on 17 October 2020. Five strengths were registered simultaneously: Estradot 25, 37.5, 50, 75, and 100 microgram transdermal patches.