Oestradiol/ Norgestrel/ Oestradiol

Registered South African indications:

• Regulation of menstrual cycle
• Menopause

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Personal and family history of breast cancer
• Severe migraine
• Markedly impaired liver function, acute liver disease (e.g. cholestatic jaundice), or a benign or malignant liver tumour, which developed during the use of oestrogen-containing medicines, or a history of liver disease as long as liver function tests have failed to return to normal
• Dubin-Johnson syndrome or Rotor syndrome
• Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial or genital carcinoma)
• Undiagnosed abnormal, vaginal or genital bleeding
• Untreated endometrial hyperplasia
• Congenital disturbances of lipid metabolism
• Otosclerosis with deterioration during pregnancy
• Cerebral vascular or coronary artery disease
• Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)
• Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
• Previous deep-vein thrombosis
• Previous pulmonary embolism
• Inherited thrombophilia
• Known with inherited genetic mutations: BRCA 1 and BRCA 2 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)
• Porphyria
• Pregnancy or suspected pregnancy

Cautions

• Breastfeeding
• Renal impairment
• Leiomyoma
• Endometriosis
• Risk factors for thromboembolic disorders
• Risk factors for oestrogen dependent tumours
• Hypertension
• Hepatic disorders
• Diabetes mellitus
• Cholelithiasis
• Migraine or severe headaches
• Systemic lupus erythematosus
• Chorea minor
• History of endometrial hyperplasia
• Epilepsy
• Asthma
• Otosclerosis
• Hereditary angioedema
• Cardiac dysfunction
• Prolonged use
• Hypertriglyceridaemia
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorbtion

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

Regulation of menstrual cycle
Hormone replacement therapy for menopause

Estradiol valerate 2mg

• Oral (tab): 1 tablet, dly for 11 days

THEN

Estradiol valerate/ norgestrel
2/0.5 (mg)

• Oral (tab): 1 tablet, dly for 10 days

THEN

Inactive tablets

• Oral (tab): 1 tablet, dly for 7 days

If still menstruating: Initiate estradiol valerate 2mg on day 1 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

If menstruation has stopped, or is infrequent or sporadic, then 1st tablet can be taken at any time

Withdrawal bleeding can be expected 2-4 days after completion of estradiol valerate 2mg/norgestrel 0.5mg tablets

NOTE: This is not a contraceptive product

Missed tablets: See additional prescribing points

Not indicated for use in children

Contraindicated in early menstrual periods (before the age of 12 years)

Pregnancy

• Contraindicated

Breastfeeding

• Not indicated for use in breastfeeding women
• Mothers breastfeeding their infants should not be treated with this combination product

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Marked impaired liver function: Contraindicated
• Acute liver disease (e.g. cholestatic jaundice), or a benign or malignant liver tumour, which developed during the use of oestrogen-containing medicines, or a history of liver disease (as long as liver function tests have failed to return to normal): Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Contraindicated

Drugs in Sport

• Permitted - No warnings 

Central Nervous System Disorders

• Depressed mood
• Anxiety
• Headache
• Migraine
• Dizziness
• Fatigue
• Dementia

Cardiovascular Disorders

• Palpitations
• Venous thromboembolism
• Myocardial infarction
• Stroke

Gastrointestinal Disorders

• Abdominal pain 
• Nausea and vomiting
• Dyspepsia
• Bloating

Hepatobiliary Disorders

• Gallbladder disease

Genitourinary Disorders

• Increased libido
• Decreased libido
• Abnormal vaginal bleeding
• Dysmenorrhoea
• Vaginal discharge
• Premenstrual-like syndrome
• Endometrial tumours
• Breast tumours
• Ovarian malignancy

Endocrine and Metabolic Disorders

• Increased weight 
• Decreased weight 
• Breast pain
• Breast enlargement

Musculoskeletal Disorders

• Muscle cramps

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritis
• Erythema nodosum
• Urticaria
• Hirsutism
• Acne
• Oedema
• Chloasma
• Vascular purpura

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

Sensory Disorders

• Visual disturbances
• Contact lens intolerance

• CYP450 inducers
• Ritonavir
• Nelfinavir
• Antidiabetic agents

• Pelvic examination
• Breast examination
• Pregnancy test
• Blood pressure

Specific cases may require

• Hepatic function

Missed dose

• <12hrs late: take tablet as soon as possible
• >12hrs late: leave the missed tablet in the pack and the next tablet taken at the right time

Estradiol binds to estrogen receptors in target tissues (female organs, breasts, hypothalamus and pituitary) which leads to the formation of messenger RNA which interacts with ribosomes to produce specific proteins that express the effect of estrogen upon the target cell.

Norgestrel binds to estrogen and progesterone receptors in target tissues (female organs, breasts, hypothalamus and pituitary). This leads to decreased gonadotropin releasing hormone release and blunting of the luteinizing hormone surge.

COMBINATION PREPARATIONS

Oestradiol valerate/ Norgestrel/ Oestradiol valerate

Tablet 2mg/0.5mg/2mg

• Postoval (Pharmacare) originator