Dosage

Adults
Elderly
Patients with Renal Impairment
Patients with Hepatic Impairment
Additional Dosage Information

Estradiol with Levonorgestrel once weekly patch (continuous therapy)

Apply one patch once a week, that is replacing each patch every 7 days.

This is a continuous combined hormone replacement therapy (HRT) treatment without a treatment-off phase: as one patch is removed, the next is applied immediately.

In women with amenorrhoea and not taking HRT or women transferring from another continuous combined HRT product, treatment may be started on any convenient day.

In women transferring from sequential HRT regimens, treatment should start immediately after their withdrawal bleeding has ended.

Remove each used patch after 7 days and apply a fresh patch to a different site.

Estradiol with Levonorgestrel once weekly patch (sequential therapy)

Women who are not taking hormone replacement therapy (HRT) or women switching from continuous combined HRT may start treatment on any convenient day.

Women transferring from a sequential HRT regimen should begin treatment the day following completion of the previous regimen.

Apply one phase I patch (estradiol only) once weekly for the first two weeks followed by one phase II patch (estradiol and levonorgestrel) weekly for the next two weeks.

Remove each used patch after 7 days and apply a fresh patch to a different site.

Precautions and Warnings

Only for use in the treatment of menopausal symptoms which adversely affect the quality of life.

Assessment of each woman before taking hormone replacement therapy (and at regular intervals thereafter) should include a personal and family medical history.
Clinical examination of pelvis and breast should be performed where clinically indicated rather than as a routine procedure.
Investigations including mammography should be carried out in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

There is an increased risk of breast cancer in women currently or recently using Hormone Replacement Therapy (HRT). The risk of breast cancer increases with the duration of treatment and returns to normal after 5 years of stopping treatment. Use with caution in patients with strong hereditary risk of breast cancer. Patients with a history of breast nodules or fibrocystic disease should be closely monitored for breast status.
Use with caution in patients with strong hereditary risk of breast cancer. Patients with a history of breast nodules or fibrocystic disease should be closely monitored for breast status.

Examinations to rule out endometrial abnormalities should be undertaken at regular intervals. Prolonged monotherapy with oestrogens increases the risk of endometrial hyperplasia and carcinoma in postmenopausal women unless supplemented by sequential administration of a progestogen to protect the endometrium. The addition of a progestogen for at least 12 days of the cycle in non-hysterectomised women greatly reduces this risk. Unless there is a previous diagnosis of endometriosis it is not recommended to add a progestogen in hysterectomised women.
Breakthrough bleeding and spotting may occur during the first months of treatment. If such bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, possibly including endometrial biopsy to exclude endometrial malignancy.

Prolonged use ( 5 - 10 years ) may be associated with an increase risk of ovarian cancer.

Not to be used for oral contraception. Barrier methods of contraception are advised.

The following conditions may deteriorate on HRT and close monitoring of the patient is advised if any of the conditions are present, have occurred previously and/or have been aggravated during pregnancy or previous hormone treatment:
Leiomyoma (uterine fibroids) or endometriosis
A family history of, or risk factors for, thromboembolic disorders (see below)
Risk factors for oestrogen dependent tumours, e.g. 1st degree heredity for breast cancer
Hypertension
Liver disorders (e.g. liver adenoma)
Diabetes mellitus with or without vascular involvement
Cholelithiasis
Migraine or (severe) headache
Systemic lupus erythematosus
A history of endometrial hyperplasia
Endometriosis

If worsening of any of the above conditions is diagnosed or suspected during HRT, the benefits and risks of HRT should be reassessed based on the individual case.

Although included in product literature some sources consider the evidence for caution in the following conditions to be inconclusive:
Hypertension
Epilepsy
Asthma
Otosclerosis
Sickle-cell disease
Melanoma
Multiple sclerosis.

It is essential that patients with epilepsy are kept under surveillance and HRT be stopped if there is an increase in epileptic seizures.

Treatment should be discontinued immediately and the appropriate investigations carried out if any of the following occurs:
Jaundice or deterioration in liver function
Significant increase in blood pressure
Severe abdominal pain
New onset of migraine-type headache, disturbances of vision or hearing or other signs and symptoms suggestive of cerebrovascular accident
Onset of severe depression
Pregnancy.

Caution is advised in patients with a history of oestrogen related jaundice and pruritus.

Diabetic patients should be monitored during initiation of therapy until further information is available on the effect of oestrogens on carbohydrate metabolism.

Caution is advised in conditions which may be aggravated by fluid retention (e.g. cardiac or renal impairment).

Use with caution in severe hypocalcaemia.

Pre-existing uterine leiomyomas or fibroids may become enlarged during oestrogen therapy.

Women with endometriosis should be carefully monitored.

The presence of a personal or strong family history of recurrent thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophilic predisposition. HRT treatment should be stopped until a definitive diagnosis has been made or anticoagulant treatment initiated.
Use of HRT in patients with a history of recurrent venous thromboembolism (VTE) or known thrombophilic states already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.

Generally recognised risk factors for VTE include a personal history or family history, severe obesity (Body Mass Index >30kg per metre squared), systemic lupus erythematosus with phospholipid antibodies. The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery.
As in all post-operative patients scrupulous attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to temporarily stopping HRT 4-6 weeks earlier, if possible. Treatment should not be restarted until the patient is fully mobilised.
Women taking hormone replacement therapy may be at increased risk of deep-vein thrombosis during travel involving long periods of immobility (over 5 hours). The risk may be reduced by appropriate exercise during the journey and possibly by wearing elastic hosiery.

Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

Discontinue treatment with HRT if VTE develops after initiating therapy.

Women with familial hypertriglyceridaemia should be monitored closely due to the increased risk of pancreatitis.

HRT does not prevent coronary heart disease and should not be used for this purpose.
There is an increased risk of coronary heart disease in women starting HRT more than 10 years after the menopause.

HRT therapy has been associated with increased risks of:
ischaemic stroke
dementia
gall bladder disease

Oestrogens increase the levels of circulating thyroid hormone, corticosteroids and sex steroids.

Should the patient complain of severe upper abdominal symptoms, enlarged liver of signs of abdominal haemorrhage consider the possibility of a hepatic tumour.

Exogenous oestrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should minimise exposure to the sun or ultraviolet radiation whilst taking HRT.

St John's Wort may induce the metabolism of oestrogens and progestogens.

Contact sensitisation is known to occur with all topical applications. Although extremely rare, patients who develop contact sensitisation to any of the components of the patch should be warned that severe hypersensitivity reaction may occur with continuous exposure to the causative agent.

CSM Warnings

Recently conducted randomised clinical trials have failed to show any benefit of hormone replacement therapy in the prevention of coronary heart disease. These studies showed a slight tendency to increased rates of coronary heart disease in the first year or two of treatment, with a possible decrease in later years, both in women with a history of coronary heart disease and those without. The initiation and continuation of HRT should be based on established indications.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Should pregnancy occur, treatment should be discontinued immediately.

Estradiol has been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb (Briggs, 2011). However, some studies have failed to find a relationship with cardiovascular defects and non-genital malformations. Down's syndrome has also been associated with oestrogens as a group, but not for estradiol (Schaefer, 2007).

Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males who have been exposed to estradiol and progestogen have demonstrated a trend to have less heterosexual characteristics and fewer masculine interests than males which have not been exposed to these hormones prenatally.

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 14-17 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 ).

Lactation

Hormone replacement therapy is contraindicated during breastfeeding.

Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breastfeed (Hale, 2010). Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk (Briggs, 2011). Even though the extent of these changes is low, the changes in milk production and composition may be of nutritional importance in malnourished mothers. Because of the reasons mentioned above the use of this medication during lactation should be avoided.

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

Presentation

Estradiol with Levonorgestrel once weekly patch (continuous therapy)

Each transdermal patch contains 1.5mg of estradiol hemihydrate and 525 micrograms levonorgestrel in a patch size of 15 cm squared, releasing 50 micrograms of estradiol and 7 micrograms of levonorgestrel per 24 hours.

Estradiol with Levonorgestrel once weekly patch (sequential therapy)

Transdermal patches for phased treatment:

Phase I patch contains 1.5mg estradiol hemihydrate releasing approximately 50 micrograms of estradiol per 24 hours

Phase II patch contains 1.5mg estradiol hemihydrate and 1.5mg levonorgestrel releasing approximately 50 micrograms of estradiol and 10 micrograms of levonorgestrel per 24 hours

Drugs List

estradiol with levonorgestrel 50microgram+7microgram/24hour once weekly patch

FEMSEVEN CONTI patch

Therapeutic Indications

Uses

Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women with an intact uterus.

Use the lowest effective dose for the shortest possible time and review the need to continue treatment at least annually.

The preparation for continuous therapy is intended for use in women whose last menstrual period was at least 12 months ago.

Dosage

Adults