Estradiol

Registered South African indications:

• Atrophic vaginitis due to oestrogen deficiency

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known history (personal and/or family) or suspected breast cancer
• Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer)
• Undiagnosed genital bleeding
• Untreated endometrial hyperplasia
• Previous or current venous thromboembolism (deep vein thrombosis (DVT), pulmonary embolism)
• Inherited thrombophilia or known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)
• Active or recent arterial thromboembolic disease (e.g. coronary artery disease, angina pectoris, myocardial infarction, stroke)
• Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
• Porphyria
• Patients known with inherited genetic mutations: BRCA1 and BRCA2 genes
• Early menstrual periods (before the age of 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 exposure to diethylstilbestrol (DES)
• Pregnancy

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Known, past or suspected breast cancer
• Known, past or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer)
• Undiagnosed genital bleeding
• Untreated endometrial hyperplasia
• Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
• Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)
• Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
• Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
• Porphyria

Cautions 

• Renal impairment
• Elderly
• Short narrow vaginas due to previous surgery or the effect of atrophy
• Uterovaginal prolapse severe enough to prevent retention of the ring
• Constipation
• Conditions causing poor skin integrity
• Uterine fibroids or endometriosis
• Risk factors for thromboembolic disorders
• Risk factors for oestrogen dependent tumours
• Hypertension
• Diabetes mellitus 
• Cholelithiasis
• Migraine or (severe) headache
• Systemic lupus erythematosus
• A history of endometrial hyperplasia
• Epilepsy
• Asthma
• Otosclerosis
• Intact uterus
• Prolonged use
• Pre-existing hypertriglyceridemia 
• Hereditary angioedema

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

South African registered indications and dosages

Atrophic vaginitis due to oestrogen deficiency

• Intravaginal (tab): Initial: 10μg, daily using an applicator, for 2 weeks; Maintenance: 10μg, 2 times weekly

Treatment may be started on any convenient day

May be used by women with or without an intact uterus

For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration should be used

During treatment, especially during the first 2 weeks, absorption may be seen but as plasma estradiol levels usually do not exceed normal postmenopausal levels the addition of a progestagen is not recommended

Missed dose: If a dose is forgotten, it should be used as soon as the patient remembers. A double dose should be avoided

See additional prescribing points for administration directions

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

South African registered indications and dosages

Atrophic vaginitis due to oestrogen deficiency

Intravaginal (tab)

• Younger than 12 years: Contraindicated
• 12 years and older: No information available

See contraindications for additional information

Pregnancy

South African recommendations

• Contraindicated
• Estradiol vaginal tablets are contraindicated during pregnancy
• If pregnancy occurs during treatment should be withdrawn immediately

Recommendations in other jurisdictions

• Not indicated for use in pregnant women
• If pregnancy occurs during medication with estradiol, treatment should be withdrawn immediately
• The results of most epidemiological studies to date relevant to inadvertent foetal exposure to oestrogens indicate no teratogenic or foetotoxic effects

Breastfeeding

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Not indicated for use in breastfeeding women

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No information available

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  Patients with cardiac or renal dysfunction should be closely monitored in the initial weeks of treatment due to the potential of fluid retention caused by oestrogens, such as estradiol

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  The experience of treating women older than 65 years is limited

Central Nervous System Disorders

• Dizziness
• Headache
• Migraine
• Anxiety
• Depression
• Changes in libido
• Mood disturbances

Cardiovascular Disorders

• Venous thrombosis
• Pulmonary embolism

Gastrointestinal Disorders

• Nausea
• Bloating
• Abdominal pain
• Abdominal pain
• Abdominal discomfort
• Anorectal discomfort

Hepatobiliary Disorders

• Gallbladder disease

Genitourinary Disorders

• Bladder discomfort
• Vulvovaginal discomfort
• Pruritus genitalis
• Vaginal erosion
• Vaginal ulceration
• Urinary tract infection
• Vaginal infection
• Vaginitis
• Abnormal uterine bleeding
• Breast pain
• Breast tenderness
• Breast enlargement
• Breast discharge
• Leukorrhoea
• Change in menstrual flow
• Change in cervical ectropion and secretion

Endocrine and Metabolic Disorders

• Changes in weight 
• Increased triglycerides

Musculoskeletal Disorders

• Arthralgias
• Leg cramps

Skin and Subcutaneous Tissue Disorders

• Generalised pruritus
• Hyperhidrosis
• Alopecia
• Chloasma/melasma
• Hirsutism
• Pruritus
• Rash
• Oedema

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

Sensory Disorders

• Intolerance to contact lenses

• CYP450 inducers
• Ritonavir 
• Nelfinavir
• St John's wort
• Other vaginal agents
• Antidiabetic agents
• Thyroid therapy
• Diethylstilbestrol (previous exposure)

• Blood pressure
• Papanicolaou smear
• Breast examination
• Mammogram

Specific cases may require

• Endometrial sampling
• Blood glucose
• Lipid profile
• Thyroid function

Administration directions

• Open the blister pack at the plunger end
• Insert the applicator in the vagina until resistance is met (8-10cm)
• Release the tablet by pressing the plunger
• Withdraw the applicator and discard (may be disposed together with household waste)

Synthetic 17β-estradiol is chemically and biologically identical to endogenous human estradiol. 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-estradiol 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.

Vaginal tablet 10μg

• Vagifem ( Novo Nordisk) Originator

Also available in the following forms: Oral tablet, gel, implant and transdermal patch