Estradiol with (estradiol and norethisterone) oral
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Tablets containing estradiol 2mg
Tablets containing estradiol 2mg and norethisterone 1mg
HRT for treatment of oestrogen deficiency in women with intact uterus
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture
For initiation and continuation of treatment, the lowest effective dose for the shortest duration should be used.
One estradiol tablet to be taken daily for the first 16 days, followed by one estradiol with norethisterone combined tablet daily for the next 12 days. The next 28 day cycle should then commence without a break.
Treatment is continuous, so when one course is finished the next should be started the next day without an interval. A menstrual-type vaginal bleed usually occurs at the end of the treatment cycle or after administration of the last estradiol and norethisterone tablet.
In women who are still menstruating, the first tablet should be taken on the fifth day of bleeding.
Patients who are not menstruating, or in whom bleeding is infrequent or sporadic, may take the first tablet at any time.
Patients changing from a cyclic or continuous sequential HRT preparation should complete the cycle and then start treatment without a break in therapy.
Patients changing from a continuous combined HRT preparation may begin therapy at any time if amenorrhoea is established or otherwise start on the first day of bleeding.
(See Dosage; Adults)
Additional Dosage Information
Missed or forgotten tablets should be taken as soon as is convenient. However if a whole day has passed the missed tablet should be discarded and the next tablet taken at the usual time. A missed dose may increase the likelihood of breakthrough bleeding and spotting.
Breakthrough bleeding may occasionally occur in the first few weeks after initiating treatment but will usually settle.
Suspected hormone dependent neoplasm
Abnormal liver function test
Acute hepatic disorder
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder without anticoagulant therapy
History of venous thromboembolism
Protein C deficiency disease
Protein S deficiency disease
Recent arterial thromboembolic disorder
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage
Precautions and Warnings
Body mass index above 30kg per square metre
Family history of breast cancer
Family history of venous thromboembolism
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Fibrocystic breast disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
History of chloasma
History of endometrial hyperplasia
History of endometriosis
History of jaundice
History of thromboembolic disorder
Sickle cell disease
Systemic lupus erythematosus
Assess family medical history prior to commencing treatment
Not all available brands are licensed for all indications
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Abnormal and/or irregular bleeding should be investigated
Advise patients of risks/benefits & review need for treatment regularly
Discontinue treatment if patient develops seizures
Monitor hepatic function in patients with history of hepatic disease
Advise patient that changes in their breasts should be reported to Dr/nurse
Advise patient to contact a doctor if symptoms of thromboembolism develop
Discontinue at the onset of severe depression
Increased risk of VTE during travel involving >5hr immobilisation
May interfere with certain laboratory measurements
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of jaundice
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if cerebrovascular disorders occur
Discontinue if cholestasis develops
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if first occurrence or worsening of visual disturbances
Discontinue if pre-existing uterine fibroids increase in size
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden pain in the chest occurs
Discontinue if symptoms due to endometriosis are exacerbated
Advise patient not to take St John's wort concurrently
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT
Hormone replace therapy (HRT) should only be initiated for postmenopausal symptoms that adversely affect quality of life. A careful appraisal of the benefits and risks should be undertaken at least annually and treatment should only be continued as long as the benefit outweighs the risk.
For the treatment of menopausal symptoms the benefits of short-term HRT are considered to outweigh the risks in the majority of women.
In all cases, it is good practice to use the lowest effective dose for the shortest possible time and to review the need to continue treatment at least annually.
For postmenopausal women over 50 years who are at an increased risk of bone fracture, HRT should be used to prevent osteoporosis only in those who are intolerant of, or contraindicated for, other osteoporosis therapies.
Pregnancy and Lactation
Contraindicated during pregnancy.
Stop treatment immediately if pregnancy is suspected.
Data on a limited number of exposed pregnancies indicate adverse effects of norethisterone on the foetus. At higher doses than those used for HRT, masculisation of female foetuses has been observed. The results of most epidemiological studies to date relevant to foetal exposure to combinations of oestrogens with progestogens, indicate no teratogenic or foetotoxic effects.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Contraindicated in breastfeeding.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Encourage patients to participate in the national breast cancer screening programme and the national cervical cancer screening programme as appropriate for their age. Breast awareness should also be encouraged and patients advised to report any changes in their breasts to their doctor or nurse
Advise patients to contact their doctor if they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
Stop treatment immediately if pregnancy is suspected.
Aggravation of porphyria
Allergic skin reactions
Change in amount of cervical secretion
Change in carbohydrate metabolism
Changes in libido
Deep vein thrombosis (DVT)
Exacerbation of epilepsy
Exacerbation of varicose veins
Increase in plasma triglyceride concentration
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased risk of ovarian cancer
Increased size of uterine fibroids
Intolerance to contact lenses
Liver function disturbances
Peripheral vascular disorders
Steepening of corneal curvature
Effects on Laboratory Tests
The use of oestrogen may influence the laboratory results of certain endocrine tests and liver enzymes.
HRT increases the density of mammographic images and may adversely affect the radiological detection of breast cancer.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: October 2013
Summary of Product Characteristics: Clinorette - Estradiol 2mg / Norethisterone 1mg tablets. Resource Medical UK Ltd. March 2013.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 December 2022
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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