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Estradiol transdermal low strength

Updated 2 Feb 2023 | Oestrogens and HRT

Presentation

Transdermal patches containing estradiol (less than 50 microgram per 24 hours).

Drugs List

  • ESTRADERM MX 25microgram/24hour patch
  • estradiol 25microgram/24hour twice weekly patch
  • estradiol 37.5microgram/24hour twice weekly patch
  • ESTRADOT 25microgram/24hour patch
  • ESTRADOT 37.5microgram/24hour patch
  • EVOREL 25 patch
  • Therapeutic Indications

    Uses

    Replacement therapy for oestrogen deficiency symptoms

    Hormone replacement therapy [HRT] for oestrogen deficiency symptoms in peri and postmenopausal women.

    Dosage

    For initiation and continuation of treatment, the lowest effective dose for the shortest duration should be used and reviewed annually.

    In women with a uterus, an approved progestogen for addition to oestrogen therapy, should be added for at least 12 to 14 days each cycle to oppose the production of an oestrogen-stimulated hyperplasia of the endometrium. Unless there is a previous diagnosis of endometriosis, it is not recommended to add a progestogen in hysterectomised women.

    Adults

    One transdermal patch should be applied weekly or twice weekly (every 3 to 4 days) on a continuous basis in accordance with the manufacturer's recommendations.

    Some weekly preparations may be applied on a cyclical basis. Where this is the case, one transdermal patch should be applied on a weekly basis for 3 consecutive weeks, followed by a patch free interval of 7 days before beginning the next treatment course.

    If after 3 months there is insufficient response in the form of alleviated symptoms, the dose can be increased to not more than a maximum dose of 100 micrograms per 24 hours.

    Starting treatment:

    Post-menopausal women with an intact uterus not currently receiving HRT, those transferring from a continuous combined or oestrogen only HRT regimen or women who have had a hysterectomy may begin treatment at any time.

    Post-menopausal women with an intact uterus transferring from a cyclical HRT regimen should begin treatment the day after completing the prior treatment course.

    Women with established amenorrhoea or women who are experiencing prolonged intervals between menses treatment may begin at any time. Women with an intact uterus who are still menstruating should begin treatment within five days of the onset of bleeding.

    Additional Dosage Information

    If the patient forgets to change their patch it should be changed as soon as is practical. If a patch has been forgotten or falls off, it may be reapplied if possible, if not then a new patch should be applied for the remainder of the dose interval.

    To aid compliance it is recommended that the patient then continues to change the patch on the original scheduled day(s).

    Contraindications

    Abnormal liver function test
    Acute hepatic disorder
    Breast cancer
    Breastfeeding
    History of breast cancer
    History of venous thromboembolism
    Oestrogen dependent neoplasm
    Porphyria
    Pregnancy
    Recent arterial thromboembolic disorder
    Thromboembolic disorder
    Thrombophilia
    Uncontrolled endometrial hyperplasia
    Undiagnosed gynaecological haemorrhage

    Precautions and Warnings

    Body mass index above 30kg per square metre
    Family history of breast cancer
    History of cholestatic jaundice
    History of recurrent spontaneous abortion
    Patients over 65 years
    Predisposition to thromboembolic disease
    Prolonged immobilisation
    Recent surgery
    Severe headache
    Abnormal mammography
    Asthma
    Cardiac impairment
    Cholelithiasis
    Diabetes mellitus
    Endometriosis
    Epileptic disorder
    Gall bladder disorder
    Hepatic disorder
    Hepatic impairment
    Hereditary angioneurotic oedema
    History of chloasma
    History of endometrial hyperplasia
    History of endometriosis
    History of thromboembolic disorder
    Hypertension
    Hypertriglyceridaemia
    Migraine
    Otosclerosis
    Renal impairment
    Systemic lupus erythematosus
    Uterine fibroids

    Add progestogen for 12-14 days each cycle for those with an intact uterus
    Assess family medical history prior to commencing treatment
    Exclude breast cancer before treatment
    Exclude oestrogen dependent neoplasm before treatment
    Do not apply on or near breasts
    Do breast & pelvic exam. before & during treatment if clinically indicated
    Abnormal and/or irregular bleeding should be investigated
    Advise patients of risks/benefits & review need for treatment regularly
    Discontinue treatment if patient develops seizures
    Advise patient of thromboembolic symptoms and to report them if they occur
    Advise patient that changes in their breasts should be reported to Dr/nurse
    Discontinue at the onset of severe depression
    Increased risk of VTE during travel involving >5hr immobilisation
    May interfere with certain laboratory measurements
    Discontinue 4 - 6 weeks before major surgery
    Advise patient to seek advice at first indications of pregnancy
    Discontinue at first signs of jaundice
    Discontinue at first signs of thrombophlebitis or thromboembolism
    Discontinue if angioedema occurs
    Discontinue if cerebrovascular disorders occur
    Discontinue if cholestasis develops
    Discontinue if first appearance of migraine or severe or frequent headache
    Discontinue if first occurrence or worsening of hearing disturbances
    Discontinue if first occurrence or worsening of migraine/severe headache
    Discontinue if first occurrence or worsening of visual disturbances
    Discontinue if liver function deteriorates
    Discontinue if severe abdominal symptoms develop
    Discontinue if significant rise in blood pressure occurs
    Discontinue if sudden breathlessness (or cough with blood stained sputum)
    Discontinue if sudden pain in the chest occurs
    Discontinue if symptoms due to endometriosis are exacerbated
    Advise patient not to take St John's wort concurrently
    Female: Not for contraception.Use non-hormonal contraception, if required
    Advise patient of increased risk of breast cancer vs benefits of HRT
    Women with a history of chloasma should avoid exposure to sun/UV light

    Hormone replacement therapy (HRT) should only be considered for patients whose symptoms adversely affect quality of life. An annual careful appraisal of the risks and benefits should be undertaken. When carrying out initial medical examinations of patients, ensure that investigations (including appropriate imaging tools, e.g. mammography) are carried out in accordance with currently accepted screening practices.

    There is an increased risk of breast cancer in women currently or recently using Hormone Replacement Therapy (HRT). The risk of breast cancer increases with the duration of treatment and, after stopping HRT, the risk will decrease with time. When HRT lasts for more than 5 years, the risk may persist for 10 years or more.

    Ovarian cancer is much rarer than breast cancer. Evidence suggests a slight increased risk in women taking estradiol, which becomes apparent within 5 years of use and diminishes over time after stopping. Examinations to rule out endometrial abnormalities should be undertaken at regular intervals. Prolonged monotherapy with oestrogens increases the risk of endometrial hyperplasia and carcinoma in postmenopausal women unless supplemented by sequential administration of a progestogen to protect the endometrium.
    Breakthrough bleeding and spotting may occur during the first months of treatment. If such bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, possibly including endometrial biopsy to exclude endometrial malignancy. The presence of a personal or strong family history of recurrent thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophilic predisposition. Estradiol treatment should be stopped until a definitive diagnosis has been made or anticoagulant treatment initiated.

    Oestrogenic effects e.g. breast discomfort / tenderness, water retention and bloating may be observed at the start of treatment, particularly in patients receiving hormone replacement for the first time. If symptoms persist for more than 6 weeks the patient should be advised to contact their doctor.

    Pregnancy and Lactation

    Pregnancy

    Estradiol is contraindicated during pregnancy.

    Should pregnancy occur, treatment should be discontinued immediately.

    Estrogens have been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb. However, some studies have failed to find a relationship with cardiovascular defects and non-genital malformations. Down's syndrome has also been associated with oestrogens as a group, but not for estradiol.

    Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males who have been exposed to estradiol and progestogen have demonstrated a trend to have less heterosexual characteristics and fewer masculine interests than males which have not been exposed to these hormones prenatally.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Lactation

    Estradiol is contraindicated during breastfeeding.

    Estrogens use in early postpartum may reduce volume of milk produced and protein content (Hale, 2014). Estradiol has been used to suppress postpartum breast engorgement in patients who did not desire to breastfeed. In a study using six lactating women, vaginal administration of 50mg or 100mg of estradiol resulted in less than 10% of dose in breast milk.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

    Counselling

    Encourage patients to participate in the national breast cancer screening programme and the national cervical cancer screening programme as appropriate for their age.

    Advise patients to avoid applying the patch to the same site twice running, applying to areas of skin with major folds, areas subject to chafing by clothes or around the waist.

    Advise patients that patches should never be applied to or near the breasts.

    Advise patient that forgetting to change a patch on schedule may increase the likelihood of break-through bleeding or spotting.

    If the patch becomes detached in the bath allow the skin to cool before applying new patch to avoid excessive absorption.

    Advise patients that once applied, the transdermal patch has to be covered by clothes to avoid direct exposure to sunlight.

    Advise patients to fold the patch in two after use, with the adhesive surface to the inside and dispose of it with normal household solid waste.

    Advise patients the patch should be applied to clean, dry, healthy skin which is neither irritated nor grazed, free from cream, lotion or other oily product.

    Side Effects

    "Spotting" bleeding
    Abdominal cramps
    Acne
    Aggravation of porphyria
    Allergic skin reactions
    Alopecia
    Anaphylaxis
    Angioedema
    Arthralgia
    Asthenia
    Back pain
    Benign and malignant liver changes
    Bloating
    Breakthrough bleeding
    Breast enlargement
    Breast pain
    Breast secretion
    Breast tenderness
    Cerebrovascular accident
    Cervical erosion
    Change in menstrual flow
    Changes in cervical secretion
    Changes in libido
    Chloasma
    Cholestatic jaundice
    Chorea
    Contact dermatitis
    Contact lenses may irritate
    Cystitis-like syndrome
    Deep vein thrombosis (DVT)
    Dementia
    Depression
    Diarrhoea
    Dizziness
    Dry skin
    Dysmenorrhoea
    Dyspepsia
    Dyspnoea
    Endometrial hyperplasia
    Erythema at application site
    Erythema multiforme
    Erythema nodosum
    Exacerbation of epilepsy
    Exacerbation of hypocalcaemia
    Exacerbation of otosclerosis
    Exacerbation of pre-existing asthma
    Exacerbation of varicose veins
    Exanthema
    Fibrocystic breast changes
    Flatulence
    Fluid retention
    Gallbladder disease
    Gallstones
    Genital candidiasis
    Headache
    Hirsutism
    Hypertension
    Increase in plasma triglyceride concentration
    Increased risk of breast cancer
    Increased risk of endometrial cancer
    Increased risk of oestrogen-dependent neoplasms
    Increased risk of ovarian cancer
    Increased size of uterine fibroids
    Insomnia
    Lability of affect
    Leg cramps
    Liver function disturbances
    Malaise
    Migraine
    Mood changes
    Myalgia
    Myocardial infarction
    Nausea
    Nervousness
    Oedema
    Palpitations
    Pancreatitis
    Paraesthesia
    Peripheral vascular disorders
    Premenstrual-like syndrome
    Pruritus
    Pulmonary embolism
    Rash
    Reduced carbohydrate tolerance
    Skin discolouration
    Skin necrosis
    Sodium retention
    Steepening of corneal curvature
    Thromboembolic disorders
    Thromboembolism
    Urticaria
    Vaginal candidiasis
    Vaginal discharge
    Vaginitis
    Vascular purpura
    Visual disturbances
    Vomiting
    Weight changes

    Effects on Laboratory Tests

    Estradiol may increase the density of mammographic images and adversely effect the detection of breast cancer.

    The use of oestrogen may influence the laboratory results of certain endocrine tests and liver enzymes.

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full Review Date: February 2018.

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Medications and Mothers' Milk, 16th Edition (2014) Hale, T. Hale Publishing, Amarillo, Texas.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

    Summary of Product Characteristics: Elleste Solo MX 40microgram Transdermal Patch. Meda pharmaceuticals. Revised March 2012.

    Summary of Product Characteristics: Elleste Solo MX80 mcg Transdermal Patch. Meda Pharmaceuticals. Revised March 2012.

    Summary of Product Characteristics: Estraderm TTS. Novartis Pharmaceuticals UK Ltd. Revised August 2011.

    Summary of Product Characteristics: Estraderm MX 25. Novartis Pharmaceuticals UK Ltd. Revised August 2011.

    Summary of Product Characteristics: Estraderm MX 50. Novartis Pharmaceuticals UK Ltd. Revised August 2011.

    Summary of Product Characteristics: Estraderm MX 75. Novartis Pharmaceuticals UK Ltd. Revised August 2011.

    Summary of Product Characteristics: Estraderm MX 100. Novartis Pharmaceuticals UK Ltd. Revised August 2011.

    Summary of Product Characteristics: Estradot 25 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised November 2020.

    Summary of Product Characteristics: Estradot 32.5 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised November 2020.

    Summary of Product Characteristics: Estradot 50 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised November 2020.

    Summary of Product Characteristics: Estradot 75 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised November 2020.

    Summary of Product Characteristics: Estradot 100 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised November 2020.

    Summary of Product Characteristics: Evorel 25 Patches. Jansen-Cilag Ltd. Revised June 2016.

    Summary of Product Characteristics: Evorel 50 Patches. Jansen-Cilag Ltd. Revised June 2016.

    Summary of Product Characteristics: Evorel 75 Patches. Jansen-Cilag Ltd. Revised June 2016.

    Summary of Product Characteristics: Evorel 100 Patches. Jansen-Cilag Ltd. Revised June 2016.

    Summary of Product Characteristics: Femseven 50. Merck Serono. Revised December 2011.

    Summary of Product Characteristics: Femseven 75. Merck Serono. Revised December 2011.

    Summary of Product Characteristics: Femseven 100. Merck Serono. Revised December 2011.

    Summary of Product Characteristics: Progynova TS 50mcg/24hrs Transdermal patch. Bayer Plc. Revised September 2012.

    Summary of Product Characteristics: Progynova TS 100mcg/24hrs Transdermal Patch. Bayer Plc. Revised September 2012.

    NAPOS. The drug database for acute porphyria.
    Available at: https://www.drugs-porphyria.org/
    Estrogens and progestogens Last revised: February 2011
    Last accessed: 05 February 2018.

    NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 February 2018.

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