UK Prescribing Information: Estradot® (estradiol hemihydrate) transdermal patch

UK Prescribing Information:  Estradot® (estradiol hemihydrate) transdermal patch.
Please refer to the Summary of Product Characteristics before prescribing

Indications: Estradot 25 mcg, 37.5 mcg, 50 mcg, 75mcg/24hours as Hormone Replacement Therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women. Estradot 50 mcg, 75 mcg, 100 mcg/24 hours patches are also licensed for the prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis.. Posology and administration: The transdermal patch is applied as continuous therapy (uninterrupted application) twice weekly to the abdomen. Oestrogen deficiency symptoms: initiate or continue at the lowest effective dose for the shortest duration, depending on patient response. If after three months of treatment, there is insufficient response, the dose can be increased. Prevention of osteoporosis: initiate treatment with an Estradot 50 microgram/24 hours patch. Adjustments can be made by using Estradot 50, 75 and 100 microgram patches. In women with an intact uterus, combine with a progestagen approved for addition to oestrogen treatment. General instructions: Addition of a progestogen in hysterectomized women is not recommended unless there is a previous diagnosis of endometriosis. Estradot should not be applied to the breasts. The site of application must be rotated, with at least 1 week interval between applications to the same site. Interruption of treatment might increase the likelihood of irregular bleeding and spotting. If symptoms of overdose occur, including breast tenderness and/or vaginal bleeding, a reduction in dosage should be considered. 

Contraindications: known, past or suspected breast cancer; known or suspected oestrogen-dependent malignant tumours; undiagnosed genital bleeding; untreated endometrial hyperplasia; previous or current venous thromboembolism; known thrombophilic disorders; active or recent arterial thromboembolic disease; acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal; known hypersensitivity to the active substance or any excipients: Porphyria. 

Warnings/Precautions: not indicated during pregnancy or lactation. HRT treatment should only be initiated or continued if postmenopausal symptoms adversely affect quality of life and if the benefit outweighs the risk. A benefit risk appraisal should be undertaken annually at minimum. HRT use in premature menopause has limited risk evidence. Before initiation, medical personal and family history and physical assessment should be performed. Regular check-ups are recommended based on clinical and individual needs. Women should report changes in their breasts to a healthcare professional. Assessment of benefits and risks should be carefully considered also in chronic anticoagulant treatment. Conditions which need supervision: The current or previous presence, and/or aggravation during pregnancy or previous hormone treatment, of any of the following conditions requires close supervision of the patient during treatment with Estradot: leiomyoma, endometriosis, risk factors for thromboembolic disorders, risk factors for oestrogen-dependent tumours, hypertension, liver disorders, diabetes mellitus with or without vascular involvement, cholelithiasis, migraine or (severe) headache, systemic lupus erythematosus, history of endometrial hyperplasia, epilepsy, asthma and otosclerosis. Reasons for immediate withdrawal of therapy: jaundice or deterioration in liver function, significant increase in blood pressure, new onset of migraine-type headache, pregnancy. Endometrial hyperplasia/caricoma: women with an intact uterus receiving oestrogens alone for long periods have a higher risk. The risk may remain elevated for at least 10 years after stopping treatment. Addition of a progestagen can prevent the excess risk. Endometrial safety of added progestagens has not been studied for Estradot 75 or 100 μg/day. Break-through bleeding and spotting may occur in the first months of therapy. If symptoms continue, investigate further. Addition of progestagens to oestrogen replacement therapy should be considered in women who have undergone hysterectomy because of endometriosis, if they are known to have residual endometriosis. Breast Cancer: an increased risk is present in women on combined oestrogen-progestagen or oestrogen-only HRT and it is dependent on the duration of HRT treatment. HRT, especially oestrogen-progestagen combined treatment, can cause an increase in the density of mammographic images and affect the radiological detection of breast cancer. Ovarian cancer: much rarer than breast cancer. Suggested risk varies. Venous thromboembolism (VTE), increased risk with HRT, more likely within the first year. If prolonged immobilisation is to follow elective surgery, temporarily stopping HRT 4 to 6 weeks earlier is recommended. Treatment should not be restarted until the woman is completely mobilised. In women with no personal history of VTE but with a first degree relative with a history of thrombosis at young age, screening may be offered after careful counselling. If VTE develops after initiating therapy, the drug should be discontinued. Coronary Artery Disease (CAD): Combined oestrogen-progestagen or oestrogen-only HRT has not shown to protect against myocardial infarction, the relative risk is slightly increased with combined oestrogen-progestan HRT. Ischaemic stroke: Combined oestrogen-progestagen and oestrogen-only therapy are associated with a higher risk. Angioedema: Cases of anaphylactic/anaphylactoid reactions have been reported. Exogenous estrogens may induce or exacerbate symptoms of hereditary and acquired angioedema. Other conditions: Oestrogens may cause fluid retention and monitoring is required for patients with cardiac or renal dysfunction. Rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported and close monitoring of pre-existing hypertriglyceridemia should occur. Increases in thyroid binding globulin, increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels or T3 levels have been reported. Free T4 and free T3 concentrations are unaltered. Corticoid binding globulin and sex-hormone-binding globulin are increased in serum leading to increased circulating corticosteroids and sex steroids. Other plasma proteins may be increased. HRT use does not improve cognitive function and there is limited evidence of increased risk of probable dementia in women who start continuous combined or oestrogen-only HRT after the age of 65. Contact sensitization can occur. ALT elevations: Caution is warranted for co-administration with the combination drug regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir and also the regimen glecaprevir/pibrentasvir in women using ethinylestradiol-containing medicinal products. 

Adverse reactions: Very Common: headache, application site reactions, erythema, breast tension and pain, dysmenorrhoea, menstrual disorder. Common: depression, nervousness, affect liability, insomnia, nausea, dyspepsia, diarrhoea, abdominal pain, abdominal distension, acne, rash, dry skin, pruritus, back pain, breast enlargement, menorrhagia, genital discharge, irregular vaginal bleeding, uterine spasms, vaginal infection, endometrial hyperplasia, pain, asthenia, oedema peripheral, weight fluctuation
Prescribers should consult the summary of product characteristics in relation to other adverse reactions

Legal classification: POM
Marketing Authorisation holder GB and NI: Sandoz Limited, Park View, Riverside Way, Watchmoor Park, Camberley, Surrey. GU15 3YL United Kingdom
Marketing Authorisation (MA) number, quantities and price:
PL 23860/0007 Estradot 25 micrograms/24 hours, transdermal patch [x8], £7.38
PL 23860/0008 Estradot 37.5 micrograms/24 hours, transdermal patch [x8], £7.39
PL 23860/0009 Estradot 50 micrograms/24 hours, transdermal patch [x8], £7.41
PL 04416/1722 Estradot 75 micrograms/24 hours, transdermal patch [x8], £8.62
PL 23860/0011 Estradot 100 micrograms/24 hours, transdermal patch [x8], £8.95

Full Prescribing Information available from: Sandoz Limited, Park View, Riverside Way, Watchmoor Park, Camberley, Surrey, GU15 3YL
Date of last revision of prescribing information: August 2024
MLR ID: MLR-0004-UK