Femoston-Conti 0.5/2.5 mg, 1/5 mg

/ Abbott

Femoston-conti 0.5 mg/2.5 mg or 1mg/ 5mg is a continuous combined HRT for oral use.
The oestrogen and the progestogen are given every day without interruption.
The dosage is one tablet per day for a 28 day cycle.
The drug should be taken continuously without a break between packs.
For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration should be used.
Femoston is indicated for the treatment of symptoms and not for prevention.
In case of no improvement of symptoms within 3 months, treatment should be stopped.
Continuous combined treatment may be started  depending on the
time since menopause and severity of symptoms. Women experiencing a natural menopause should commence treatment  12 months after their last natural menstrual bleed. For surgically induced menopause, treatment may start immediately.
Depending on the clinical response, the dosage can subsequently be adjusted.
Patients changing from a continuous sequential or cyclical preparation should complete the 28 day cycle and then change to Femoston-conti. Patients changing from another continuous combined preparation may start therapy at any time.
If a dose has been forgotten, it should be taken as soon as possible. If more than 12 hours have elapsed, treatment should be continued with the next tablet without taking the forgotten tablet. The likelihood of breakthrough bleeding or spotting may be increased.
The drug can be taken irrespectively of food intake.
Paediatric population:
There is no relevant indication for the use in the paediatric population.

Hormone replacement therapy (HRT) for estrogen deficiency symptoms in postmenopausal women at least 12 months since last menses.
men at high risk of future fractures. The drug should only be used in patients who are intolerant of other products, approved for the prevention of
osteoporosis or for whom these products are contra-indicated.
Femoston is indicated for women with an intact uterus.
Experience in treating women older than 65 years is limited.

-Known, past or suspected breast cancer
-Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer)
-Undiagnosed genital bleeding
-Untreated endometrial hyperplasia
-Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
-Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)
-Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
-Acute liver disease or a history of liver disease as long as the liver function tests have failed to return to normal
-Porphyria
-Known hypersensitivity to the active substances or to any of the excipients

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.
Medical examination/follow up
Before initiating or re-instituting HRT, a complete personal and family medical history should be taken.
Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be
reported to their doctor or nurse (see “Breast cancer” below). Investigations, including appropriate imaging tools, e.g. mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Conditions which need supervision
If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment, in particular:
-Leiomyoma (uterine fibroids) or endometriosis
-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 (see below)
-Epilepsy
-Asthma
-Otosclerosis
-Meningioma
Reasons for immediate withdrawal of therapy
Therapy should be discontinued in case 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
Endometrial hyperplasia and carcinoma
-In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods. The reported increase in endometrial cancer risk among oestrogen-only users varies from 2- to12-fold greater compared with non-users, depending on the duration of treatment and oestrogen dose. After stopping treatment risk may remain elevated for at least 10 years.
-The addition of a progestogen cyclically for at least 12 days per month /28 day cycle or continuous combined oestrogen-progestogen therapy in non-hysterectomised women can prevent the excess risk associated with oestrogen-only HRT.
-Break-through bleeding and spotting may occur during the first months of treatment. If break-through bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Breast cancer
The overall evidence suggests an increased risk of breast cancer in women taking combined oestrogenprogestogen and possibly also oestrogen-only HRT, that is dependent on the duration of taking HRT.
Combined oestrogen-progestogen therapy:
-The randomised placebo-controlled trial, the Women’s Health Initiative study (WHI), and epidemiological studies are consistent in finding an increased risk of breast cancer in women taking combined oestrogen-progestogen for HRT that becomes apparent after about 3 years.
Oestrogen-only therapy:
-The WHI trial found no increase in the risk of breast cancer in hysterectomised women using oestrogenonly HRT. Observational studies have mostly reported a small increase in risk of having breast cancer diagnosed that is substantially lower than that found in users of oestrogen-progestogen combinations.
The excess risk becomes apparent within a few years of use but returns to baseline within a few (at most five) years after stopping treatment.
HRT, especially oestrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.
Ovarian cancer
Ovarian cancer is much rarer than breast cancer. Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women taking oestrogen-only or combined oestrogen-progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping. Some other studies, including the WHI trial suggest that use of combined HRTs may be associated with a similar, or slightly smaller, risk.
Venous thromboembolism
-HRT is associated with a 1.3- to 3-fold risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of HRT than later.
-Patients with known thrombophilic states have an increased risk of VTE and HRT may add to this risk.
HRT is therefore contraindicated in these patients.
-Generally recognised risk factors for VTE include: use of oestrogens, older age, major surgery, prolonged immobilisation, obesity (BMI>30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE), and cancer. There is no consensus about the possible role of varicose veins in VTE.
As in all postoperative patients, prophylactic measures need to be considered to prevent VTE following surgery. If prolonged immobilisation is to follow elective surgery, temporarily stopping HRT 4 to 6 weeks earlier is recommended. Treatment should not be restarted until the woman is completely mobilised.
-In women with no personal history of VTE but with a first degree relative with a history of thrombosis at young age, screening may be offered after careful counselling regarding its limitations (only a proportion of thrombophilic defects are identified by screening).
If a thrombophilic defect is identified which segregates with thrombosis in family members or if the defect is ‘severe’ (e.g. antithrombin, protein S, or protein C deficiencies or a combination of defects) HRT is contraindicated.
-Women already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
-If VTE develops after initiating therapy, the drug should be discontinued. 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).
Coronary artery disease (CAD)
There is no evidence from randomised controlled trials of protection against myocardial infarction in women with or without existing CAD who received combined oestrogen-progestogen or oestrogen-only HRT.
Combined oestrogen-progestogen therapy:
The relative risk of CAD during use of combined oestrogen-progestogen HRT is slightly increased. As the baseline absolute risk of CAD is strongly dependent on age, the number of extra cases of CAD due to oestrogen-progestogen use is very low in healthy women close to menopause, but will rise with more advanced age.
Oestrogen-only:
Randomised controlled data found no increased risk of CAD in hysterectomised women using oestrogen only therapy.
Ischaemic Stroke
Combined oestrogen-progestogen and oestrogen-only therapy are associated with an up to 1.5-fold
increase in risk of ischaemic stroke. The relative risk does not change with age or time since menopause.
However, as the baseline risk of stroke is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age.
Other conditions
-Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed.
-Women with pre-existing hypertriglyceridaemia should be followed closely during oestrogen replacement or hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition.
-Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio-immunoassay) or T3 levels (by radio-immunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biological active hormone concentrations are
unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-I-antitrypsin, ceruloplasmin).
-HRT use does not improve cognitive function. There is some evidence of increased risk of probable dementia in women who start using continuous combined or oestrogen-only HRT after the age of 65.
-Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine.
-This oestrogen-progestogen combination treatment is not a contraceptive.

Very common: Headache, abdominal pain, back pain, breast pain/ tenderness.
Common: Vaginal candidiasis, depression, nervousness, migraine; dizziness, nausea, vomiting; flatulence , allergic skin reactions (e.g. rash, urticaria, pruritus), menstruation disorders (including postmenopausal, spotting, metrorrhagia, menorrhagia, oligo/ amenorrhoea, irregular menstruation, dysmenorrhoea), pelvic pain, cervical erosion , asthenic disorders (asthenia, fatigue, malaise), peripheral oedema , weight gain.
See prescribing information for full details.

No interaction studies have been performed.
The efficacy of oestrogens and progestogens might be impaired:
-The metabolism of oestrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically P450 enzymes, such as anticonvulsants (e.g. phenobarbital, carbamazepin, phenytoin) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
-Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.
-Herbal preparations containing St John’s Wort (Hypericum perforatum) may induce the metabolism of oestrogens and progestogens.
-Clinically, an increased metabolism of oestrogens and progestogens may lead to decreased effect and changes in the uterine bleeding profile.

Pregnancy
The drug is not indicated during pregnancy. If pregnancy occurs during medication, treatment should be withdrawn immediately.
There are no adequate data from the use of estradiol/dydrogesterone in pregnant women. The results of most epidemiological studies to date relevant to inadvertent fetal exposure to combinations of oestrogens and progestogens indicate no teratogenic or foetotoxic effect.
Breast Feeding
The drug is not indicated during lactation.
Fertility
The drug is not indicated during fertility.

Both estradiol and dydrogesterone are substances with low toxicity. Symptoms such as nausea, vomiting, breast tenderness, dizziness abdominal pain, drowsiness/fatigue and withdrawal bleeding could occur in cases of overdosing. It is unlikely that any specific or symptomatic treatment will be necessary.
Paediatric population
Aforementioned information is also applicable for overdosing in children.