Estradiol transdermal low strength
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Transdermal patches containing estradiol (less than 50 microgram per 24 hours).
Replacement therapy for oestrogen deficiency symptoms
Hormone replacement therapy [HRT] for oestrogen deficiency symptoms in peri and postmenopausal women.
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.
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.
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).
Abnormal liver function test
Acute hepatic disorder
History of breast cancer
History of venous thromboembolism
Oestrogen dependent neoplasm
Recent arterial thromboembolic disorder
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
Gall bladder disorder
Hereditary angioneurotic oedema
History of chloasma
History of endometrial hyperplasia
History of endometriosis
History of thromboembolic disorder
Systemic lupus erythematosus
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
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 ).
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
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.
Aggravation of porphyria
Allergic skin reactions
Benign and malignant liver changes
Change in menstrual flow
Changes in cervical secretion
Changes in libido
Contact lenses may irritate
Deep vein thrombosis (DVT)
Erythema at application site
Exacerbation of epilepsy
Exacerbation of hypocalcaemia
Exacerbation of otosclerosis
Exacerbation of pre-existing asthma
Exacerbation of varicose veins
Fibrocystic breast changes
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
Lability of affect
Liver function disturbances
Peripheral vascular disorders
Reduced carbohydrate tolerance
Steepening of corneal curvature
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.
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 ).
Last Full Review Date: February 2018.
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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.
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Estrogens and progestogens Last revised: February 2011
Last accessed: 05 February 2018.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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