Estradiol transdermal
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Transdermal patches containing estradiol.
Drugs List
Therapeutic Indications
Uses
Replacement therapy for oestrogen deficiency symptoms
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture
Hormone replacement therapy [HRT] for oestrogen deficiency symptoms in peri and postmenopausal women.
Prevention of osteoporosis in postmenopausal women at a high risk of fractures and who are intolerant or contraindicated for other drugs indicated for the prevention of osteoporosis.
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
Angina
Breast cancer
Breastfeeding
Deep vein thrombosis
History of breast cancer
History of venous thromboembolism
Myocardial infarction
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Pulmonary embolism
Recent arterial thromboembolic disorder
Thromboembolic disorder
Thrombophilic disorder
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage
Precautions and Warnings
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
Hepatic adenoma
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
Risk of pancreatitis in individuals with hypertriglyceridaemia
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
Not all available brands are licensed for all indications
Do not apply on or near breasts
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Abnormal and/or irregular bleeding should be investigated
Advise patients of risks/benefits & review need for treatment regularly
Discontinue treatment if patient develops seizures
Monitor hepatic function in patients with history of hepatic disease
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
Avoid immobilisation-treatment may cause increased risk of thromboembolism
Discontinue at the onset of severe depression
Increased risk of VTE during travel involving >5hr immobilisation
Uterine fibroids may increase in size
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 visual disturbances
Discontinue if jaundice or other evidence of hepatic impairment occurs
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 sudden, severe pain in stomach 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
There is an increased risk of breast cancer in women currently or recently using receiving estradiol treatment. The risk of breast cancer increases with the duration of treatment and returns to normal after 5 years of stopping treatment. Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.
Evidence suggests a slight increased risk of ovarian cancer 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.
The manufacturer does not recommend using estradiol during pregnancy. Should pregnancy occur, treatment should be discontinued immediately.
Estradiol has been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb (Briggs, 2015). 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 (Schaefer, 2015).
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.
Lactation
Estradiol is contraindicated during breastfeeding.
The manufacturer does not recommend using estradiol during breastfeeding. Estradiol use in early postpartum may reduce volume of milk produced and protein content (Briggs, 2015). Estradiol has been used to suppress postpartum breast engorgement in patients who did not desire to breastfeed (Hale, 2014).
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.
Advise patient of thromboembolic symptoms and to report them if they occur (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
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 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 appetite
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
Increased sweating
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
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: January 2020
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) 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.
Medications and Mothers' Milk, 16th Edition (2014) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Elleste Solo MX 40microgram Transdermal Patch. Mylan. Revised May 2018.
Summary of Product Characteristics: Elleste Solo MX80 mcg Transdermal Patch. Mylan. Revised May 2018.
Summary of Product Characteristics: Estraderm MX 25. Merus Labs Luxco S.A.R.L. Revised May 2019.
Summary of Product Characteristics: Estraderm MX 50. Merus Labs Luxco S.A.R.L. Revised June 2019.
Summary of Product Characteristics: Estraderm MX 75. Merus Labs Luxco S.A.R.L. Revised June 2019.
Summary of Product Characteristics: Estraderm MX 100. Merus Labs Luxco S.A.R.L. Revised June 2019.
Summary of Product Characteristics: Estradot 25 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised April 2019.
Summary of Product Characteristics: Estradot 37.5 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised April 2019.
Summary of Product Characteristics: Estradot 50 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised April 2019.
Summary of Product Characteristics: Estradot 75 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised April 2019.
Summary of Product Characteristics: Estradot 100 micrograms/24 hours transdermal patches. Novartis Pharmaceuticals UK Ltd. Revised April 2019.
Summary of Product Characteristics: Evorel 50 Patches, Evorel 75 Patches, Evorel 100 Patches. Theramex UK Ltd. Revised October 2019.
Summary of Product Characteristics: Femseven 50. Theramex UK Ltd. Revised February 2019.
Summary of Product Characteristics: Femseven 75. Theramex UK Ltd. Revised February 2019.
Summary of Product Characteristics: Femseven 100. Theramex UK Ltd. Revised February 2019.
Summary of Product Characteristics: Progynova TS 50mcg/24hrs Transdermal patch. Bayer Plc. Revised August 2017.
Summary of Product Characteristics: Progynova TS 100mcg/24hrs Transdermal Patch. Bayer Plc. Revised August 2017.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 January 2020
The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.org
Last accessed: 08 January 2020
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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