Conjugated Oestrogens

Registered South African indications:

• Osteoporosis
• Menopause
• Primary ovarian failure
• Amenorrhoea
• Prostate cancer
• Breast cancer
• Female hypogonadism

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients
• Hepatic impairment
• Breast cancer or history thereof
• Oestrogen-dependent malignant tumours
• Undiagnosed genital bleeding
• Untreated endometrial hyperplasia
• Venous thromboembolism  
• Thrombophilic disorders
• Arterial thromboembolic disease
• Porphyria

Cautions

• Breastfeeding
• Renal impairment
• Women older than 65 years
• Leiomyoma or endometriosis
• Risk factors for venous thromboembolism
• Risk factors for oestrogen-dependent tumours (such as first degree heredity for breast cancer)
• Hypertension
• Ischaemic stroke
• Cardiac dysfunction
• Diabetes mellitus  
• Cholelithiasis
• Migraine or severe headaches
• Systemic lupus erythematosus
• Endometrial hyperplasia or history thereof
• Epilepsy
• Asthma
• Otosclerosis
• Breakthrough bleeding or spotting after the first few months of use or after discontinuation of use
• Hypertriglyceridemia
• Gallbladder disease
• Hereditary angioedema
• Severe hypocalcaemia
• Galactose intolerance
• Lapp lactase deficiency
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrose-isomaltase insufficiency

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

Climacteric and menopausal symptoms

• Oral (tab): 0.3-1.25mg, dly, continuously or cyclically; Titrate according to response to symptoms 

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Can be given continuously or cyclically (21 days of dly treatment followed by a 7 day treatment free interval)

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Once treatment is established the lowest effective dose necessary for the relief of symptoms should be used; Patients should be re-evaluated periodically to determine if treatment for symptoms is still necessary

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See additional prescribing points

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Osteoporosis prevention and management

• Oral (tab): 0.3mg, dly, continuously or cyclically; Titrate according to bone mineral density

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Can be given continuously or cyclically (25 days of dly treatment followed by a 5 day treatment free interval)

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Dose may be adjusted based on bone mineral density and clinical response. The lowest effective dose should be used

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See additional prescribing points

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Female hypogonadism

• Oral (tab): 0.3-0.625mg, dly, continuously or cyclically; Titrate according to severity of symptoms and responsiveness of the endometrium 

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To be given cyclically (21 days of dly treatment followed by a 7 day treatment free interval) or continuously as a case-based requirement

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Primary ovarian failure
Female castration

• Oral (tab): 1.25mg, dly, administered cyclically; Titrate as needed to control symptoms

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Cyclical treatment: 3 weeks of dly treatment followed by 1 week treatment free interval

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Minimum effective dose should always be used

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Palliation of prostate carcinoma
Palliation of breast carcinoma

• Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

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

Breastfeeding

• Not indicated for use in breastfeeding women 

Renal Impairment

• Caution; no information available 

Hepatic Impairment

• Contraindicated

Elderly

• No dose adjustment recommended
  The lowest effective dose should be used

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Changes in libido
• Mood disturbances
• Irritability
• Migraine
• Headache
• Dizziness
• Anxiety
• Exacerbation of epilepsy
• Exacerbation of chorea
• Stroke
• Growth potentiation of benign meningioma
• Dementia

Cardiovascular Disorders

• Myocardial infarction
• Hypertension
• Superficial thrombophlebitis
• Venous thromboembolism

Respiratory Disorders

• Exacerbation of asthma
• Pulmonary embolism

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting
• Bloating
• Pancreatitis
• Ischaemic colitis

Hepatobiliary Disorders

• Gall bladder disease
• Cholestatic jaundice
• Enlargement of hepatic haemangiomas

Genitourinary Disorders

• Vaginitis
• Vaginal candidiasis
• Changes in menstrual flow
• Abnormal uterine bleeding
• Change in cervical ectropion and secretion
• Dysmenorrhoea
• Increased size of uterine leiomyomata
• Leucorrhoea
• Ovarian cancer
• Breast pain
• Breast tenderness
• Breast enlargement
• Fibrocystic breast changes
• Galactorrhoea
• Gynecomastia (in males)

Endocrine and Metabolic Disorders

• Increased total thyroid hormone
• Aggravation of porphyria  
• Hypocalcaemia
• Increased or decreased weight
• Glucose intolerance
• Increased triglycerides
• Dyslipidaemia

Musculoskeletal Disorders

• Arthralgia
• Leg cramps

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Pruritis
• Angioedema
• Hirsutism
• Alopecia
• Chloasma/melasma
• Erythema multiforme
• Erythema nodosum
• Vascular purpura

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reaction
• Anaphylactic reactions
• Decreased levels of antithrombin II
• Increased plasminogen antigen and activity
• Increased platelet count
• Elevated serum binding proteins

Sensory Disorders

• Retinal vascular thrombosis
• Intolerance to contact lenses
• Exacerbation of otosclerosis

Others

• Oedema
• Oestrogen-dependent benign and malignant neoplasms

• CYP3A4 inducers
• St. John's wort (Hypericum perforatum)  
• Phenobarbital
• Phenytoin
• Carbamazepine
• Rifampicin
• Rifabutin
• Nevirapine
• Efavirenz
• Dexamethasone
• CYP3A4 inhibitors
• Cimetidine
• Erythromycin
• Clarithromycin
• Ketoconazole
• Itraconazole
• Ritonavir
• Nelfinavir
• Grapefruit juice
• Metyrapone
• Anticoagulant therapy
• Thyroid replacement therapy

• Gynaecological and physical exam

Specific cases may require

• Hepatic function
• Blood glucose level
• Lipid profile
• Thyroid function

Coadministration with progestogen 

• In women with a uterus where the addition of a progestogen is necessary, it should be added for at least 12-14 days every 28 day cycle to reduce the risk to the endometrium
• Unless there is a previous diagnosis of endometriosis, it is not recommended to add a progestogen in hysterectomised women
• The benefits of the lower risk of endometrial hyperplasia and endometrial cancer due to adding progestogen should be weighed against the increased risk of breast cancer

Benefit/risk balance of use

• For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk
• Evidence regarding the risks associated with HRT in the treatment of premature menopause is limited. Due to the low level of absolute risk in younger women, however, the balance of benefits and risks for these women may be more favourable than in older women
• Increased risk of ischaemic stroke, coronary artery disease, venous thromboembolism, ovarian cancer, endometrial hyperplasia and carcinoma, and breast cancer have been noted in clinical trials

Missed dose

• If a tablet is forgotten, it should be taken as soon as the patient remembers. Therapy should then be continued as before
• If more than one tablet has been forgotten, only the most recent tablet should be taken and the patient should not take double the usual dose to make up for missed tablets

Immediate withdrawal of therapy

• Therapy should be discontinued if a contraindication is discovered and in the following situations:
  - Jaundice or deterioration in liver function
  - Significant increase in blood pressure
  - New onset of migraine-type headache
  - Pregnancy

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Tablet 0.625, Tablet 0.3mg - EML (Primary)

Tablet 1.25mg - Non-EML

Oestrogens act through binding to nuclear receptors in oestrogen-responsive tissues. Oestrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone and follicle stimulating hormone through a negative feedback mechanism. Oestrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.

Tablet 0.625

• Premarin (Pfizer) originator

Tablet 0.3mg

• Premarin (Pfizer) originator

Tablet 1.25mg

• Premarin (Pfizer) originator

Also available in the following forms: Injection and vaginal cream.