Oestradiol

Registered South African indications:

• Menopause
• Prophylaxis of postmenopausal osteoporosis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known current or past or suspected breast cancer
• Family history of breast cancer
• Known or suspected estrogen-dependent malignant tumours (e.g. endometrial cancer) or pre-malignant tumours (e.g. untreated atypical endometrial hyperplasia)
• Undiagnosed genital bleeding
• Pregnancy
• Lactation
• Active liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
• Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
• Known thrombophilic conditions
• Inherited thrombophilia
• Active or past arterial thromboembolic disease (e.g. cerebrovascular accident, myocardial infarction)
• Endometriosis
• Porphyria
• Patients known with inherited genetic mutations: BRCA 1 and BRCA 2 genes
• Early menstrual periods (before age 12 years)
• History of non-cancerous breast diseases (atypical hyperplasia or lobular carcinoma in situ)
• Previous treatment using radiation therapy to the chest or breast
• Previous treatment with diethylstilboestrol (DES)
• Depression not well controlled with treatment
• History of depression with the use of estrogen and/or progesterone/progestogen-containing medicines irrespective of the indication, dosage formulation, and route of administration

Cautions

• Renal impairment
• Premature menopause
• Leiomyomata
• Endometriosis
• Risk factors for thromboembolic disorders
• Risk factors for oestrogen-dependent tumours
• Hypertension
• Diabetes mellitus with or without vascular involvement
• Cholelithiasis
• Migraine or severe headache
• Systemic lupus erythematosus
• History of endometrial hyperplasia
• Epilepsy
• Asthma
• Otosclerosis
• Hereditary angioedema
• Mastopathy
• Cardiac dysfunction
• History of cholestatic jaundice
• Hypertriglyceridaemia
• History of chloasma gravidarum

Forms avail. in SA and covered in this monograph: pat

Prophylaxis of osteoporosis in women post-hysterectomy
Hormone replacement therapy (HRT) for menopausal symptoms in women post-hysterectomy

Oestradiol 25μg equivalent to 1.6mg
Oestradiol 37.5μg
Oestradiol 50μg equivalent to 3.2mg
Oestradiol 75μg equivalent to 4.8mg
Oestradiol 100μg equivalent to 6.4mg

• Transdermal (pat): Initial: 50μg/day patch, applied every 3-4 days; Titrate at intervals of 3 months; Maintenance: 25μg/day OR 37.5μg/day OR 50μg/day OR 75μg/day OR 100μg/day patch, applied once every 3-4 days continuously; Max: 100μg/24hrs

Oestradiol 50μg equivalent to 3.9mg
Oestradiol 100μg equivalent to 7.8mg

• Transdermal (pat): 50μg/day OR 100μg/day patch, applied once every 7 days continuously or cyclically

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Cyclical treatment: 3 weeks continuously then 1 week treatment free interval

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Once treatment has been initiated, the lowest effective dose necessary for the relief of symptoms should be established

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To reduce the risk of postmenopausal bone loss should be initiated as soon as possible after menopause

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Prophylaxis of osteoporosis in women with intact uterus
Hormone replacement therapy (HRT) for menopausal symptoms in women with intact uterus

Oestradiol 25μg equivalent to 1.6mg
Oestradiol 37.5μg
Oestradiol 50μg equivalent to 3.2mg
Oestradiol 75μg equivalent to 4.8mg
Oestradiol 100μg equivalent to 6.4mg

• Transdermal (pat): Initial: 50μg/day patch, applied every 3-4 days; Titrate at intervals of 3 months; Maintenance: 25μg/day OR 37.5μg/day OR 50μg/day OR 75μg/day OR 100μg/day patch, applied once every 3-4 days continuously; Max: 100μg/24hrs

Oestradiol 50μg equivalent to 3.9mg
Oestradiol 100μg equivalent to 7.8mg

• Transdermal (pat): 50μg/day OR 100μg/day patch, applied once every 7 days continuously or cyclically

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Oestradiol cyclical treatment: 3 weeks continuously then 1 week treatment free interval

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For both continous and cyclical oestradiol therapy: Ensure that progestogen is given

Sequentially opposed therapy: Progestogen given cyclically for 12-14 days of every 4 week cycle

Continuous combined therapy: Progestogen given continuously

Menstruation-like bleeding normally occurs 2-3 days after withdrawal of progestogen

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Once treatment has been initiated, the lowest effective dose necessary for the relief of symptoms should be established

To reduce the risk of postmenopausal bone loss, should be initiated as soon as possible after menopause

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See additional prescribing points for administration directions

Not indicated for use in children

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Early menstrual periods (before age 12 years)

Pregnancy

• Contraindicated
• Oestradiol is not indicated during pregnancy. If pregnancy occurs during use of oestradiol, treatment should be withdrawn immediately
• There are no clinical data on exposed pregnancies
• Studies in animals have not shown reproductive toxicity
• The results of most epidemiological studies to date relevant to inadvertent fetal exposure to combinations of oestrogens (and progestogens) indicate no teratogenic or foetotoxic effect

Breastfeeding

• Contraindicated

Renal Impairment

• Caution: no dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• Caution; no information available

Porphyria Information

• Contraindicated

Drugs in Sport

• Permitted - No warnings 

Central Nervous System Disorders

• Depressed mood
• Migraine
• Dizziness
• Headache
• Seizures
• Cerebrovascular accident

Cardiovascular Disorders

• Palpitations
• Myocardial infarction
• Thrombosis
• Deep vein thombosis
• Oedema

Respiratory Disorders

• Pulmonary embolism

Gastrointestinal Disorders

• Abdominal pain
• Diarrhoea
• Nausea
• Flatulence
• Abdominal distention

Hepatobiliary Disorders

• Cholelithiasis

Genitourinary Disorders

• Genital candidiasis
• Breast cancer
• Endometrial cancer
• Dysmenorrhoea
• Metrorrhagia

Endocrine and Metabolic Disorders

• Breast pain
• Breast enlargement
• Increased weight

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Pruritis
• Rash
• Angiodema
• Application site erythema
• Application site reactions

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

• CYP450 inducers
• CYP450 inhibitors
• Lamotrigine

• Pelvic examination
• Breast examination
• Cervical smear
• Blood pressure

Specific cases may require

• Blood glucose
• Hepatic function
• Lipid profile

Administration directions

• Apply to clean, dry area of the trunk below the waistline
• Do not apply to the breasts
• Sites of application should be rotated, with an interval of at least one week between applications to a particular site
• Patient can bath/shower as usual
• If patch falls off, replace with a new patch for the remainder of the dosing interval

Synthetic 17β-oestradiol is chemically and biologically identical to endogenous human oestradiol. Oestrogen mediates its effects by binding to the oestrogen receptor, which is located in various tissues such as the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Endogenous 17β-oestradiol induces and maintains the primary and secondary female sexual characteristics. It substitutes for the loss of oestrogen production in menopausal women and alleviates menopausal symptoms.

Patch 25μg (equivalent to 1.6mg)

• Estradot (Novartis) originator
• Evorel 25 (Adcock Ingram Limited) originator

Patch 37.5μg

• Estradot (Novartis) originator

Patch 50μg (equivalent to 3.2mg)

• Estradot (Novartis) originator
• Evorel 50 (Adcock Ingram Limited) originator

Patch 75μg (equivalent to 4.8mg)

• Estradot (Novartis) originator
• Evorel 75 (Adcock Ingram Limited) originator

Patch 100μg (equivalent to 6.4mg)

• Estradot (Novartis) originator
• Evorel 100 (Adcock Ingram Limited) originator

Patch 50μg (equivalent to 3.9mg)

• Climara 50 (Bayer) originator

Patch 100μg (equivalent to 7.8mg)

• Climara 100 (Bayer) originator (Discontinued)

Also available in the following forms: Gel, vaginal tablet, oral tablet and implant.

COMBINATION PREPARATIONS

Fixed preparation

Oestradiol/ Norethisterone

Patch 50μg/250μg

• Estalis (Novartis) originator

Patch (per 16cm²) 3.2mg/11.2mg

• Evorel conti (Janssen) originator

Sequential preparation

Oestradiol/ Norethisterone

Patch (per 16cm²) 3.2mg/11.2mg

• Evorel sequi (Janssen) originator