Estradiol/ Norethisterone

Registered South African indications:

• Hormone replacement therapy
• Prevent osteoporosis

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Hepatic impairment
• Breast carcinoma
• Oestrogen-dependent malignant tumours  
• Undiagnosed genital bleeding
• Current or history of venous thromboembolism
• Active or recent arterial thromboembolic disease
• Severe diabetes mellitus with vascular changes
• Dyslipidaemias
• Conditions known to worsen during pregnancy
• Porphyria
• Hypertension
• Haemoglobinopathies
• Untreated endometrial hyperplasia

Cautions 

• Renal impairment
• Elderly
• Risk factor for breast cancer
• Risk factors for estrogen dependant tumours
• Multiple sclerosis
• Leiomyoma
• Endometriosis
• Endometrial hyperplasia
• Risk factors for venous/arterial thromboembolism
• Cholelithiasis
• Severe headache
• Migraine
• Cardiac dysfunction
• Systemic lupus erythematosus
• Epilepsy
• Asthma
• Hearing loss

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

Hormone replacement therapy in females with intact uterus
Prevent estrogen deficiency related osteoporosis in post menopausal women

Sequential therapy

• Estradiol 1mg: Oral (tab): 1 tab, dly, for 16 days

THEN

• Estradiol 1mg/ Norethisterone acetate 1mg: Oral (tab): 1 tab, dly, for 12 days

Sequential therapy

• Estradiol 2mg: Oral (tab): 1 tab, dly, for 12 days

THEN

• Estradiol 2mg/ Norethisterone acetate 1mg: Oral (tab): 1 tab, dly, for 10 days

THEN

• Estradiol 1mg: Oral (tab): 1 tab, dly, for 6 days

Continuous therapy

• Estradiol 1mg/ Norethisterone 0.5mg: Oral (tab): 1 tab, dly, for 28 days

Continuous therapy

• Estradiol 2mg/ Norethisterone 1mg: Oral (tab): 1 tab, dly, for 28 days

See additional prescribing points

Take without interruption, at same time each day

Not indicated for use in children

Pregnancy

• FDA Pregnancy Category Not Rated (NR)

Breastfeeding

• Contraindicated 

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• Caution; no dose adjustment recommended 

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warning

Central Nervous System Disorders

• Depressed mood
• Nervousness
• Migraine
• Headache

Cardiovascular Disorders

• Deep  and superficial thrombophlebitis
• Pulmonary embolism
• Peripheral oedema

Gastrointestinal Disorders

• Abdominal pain
• Abdominal distension
• Nausea
• Bloating
• Flatulence

Genitourinary Disorders

• Genital candidiasis
• Vaginitis
• Uterine fibroids
• Breast oedema
• Breast cancer

Endocrine and Metabolic Disorders

• Increased weight
• Fluid retention
• Breast tenderness
• Breast pain

Musculoskeletal Disorders

• Leg pain
• Back pain

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Urticaria
• Acne
• Hirsutism
• Alopecia

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

• CYP450 inducers
• CYP450 inhibitors
• Protease inhibitors
• Non-nucleoside reverse transcritpase inhibitors

• Pelvic examination
• Breast examination
• Physical examination

Specific cases may require

• Hepatic function 
• Blood glucose 

Changing from different contraceptive methods

Transferring from sequential hormone replacement therapy regimen: Treatment should begin the day following completion of the prior regimen OR right after the withdrawal bleed has ended

Missed dose

If the patient has forgotten to take a tablet, the tablet should be taken as soon as possible within the next 12 hours. If more then 12 hours have passed, the tablet should be discarded

Initiating in special circumstances: Sequential therapy

If menstruation still regular, 1st tablet should be taken the day after the last day of menstrual bleeding; If irregular menstruation or no menstrual bleeding, start on any day

Tablet 1mg/0.5mg, Tablet 2mg/1mg - EML (Primary)

All other preparations are Non-EML

Estrogens increase the hepatic synthesis of sex hormone binding globulin, thyroid-binding globulin, and other serum proteins and suppress follicle-stimulating hormone from the anterior pituitary. Progestins slow the frequency of release of gonadotropin releasing hormone from the hypothalamus and blunt the pre-ovulatory luteinising hormone surge

COMBINATION PREPARATIONS

Fixed combinations preparations

Oestradiol/ Norethisterone

Tablet 1mg/0.5mg

• Activelle (Novo Norsdisk) originator

Oestradiol/ Norethisterone

Tablet 2mg/1mg

• Kliogest (Novo Nordisk) originator

Sequential preparations

Oestradiol/ Norethisterone

Tablet 1mg/1mg

• Estro-Pause N (Adcock)
• Novofem (Novo Nordisk) Originator

Oestradiol/ Norethisterone

Tablet 1mg/2mg

• Trisequens (Novo Nordisk) Originator