Active ingredients: Estradiol, Didrogesterone
Femoston 1/5 Conti film-coated tablets
Femoston package inserts are available for pack sizes:- Femoston 1/5 Conti film-coated tablets
- Femoston 1/10 film-coated tablets
- Femoston 2/10 film-coated tablets
Why is Femoston used? What is it for?
Femoston is a hormone replacement therapy (HRT). It contains two types of female hormones, an estrogen called estradiol and a progestin called dydrogesterone. Femoston has been used in postmenopausal women for at least 12 months.
Femoston is used for
Relieving symptoms that occur after menopause: During menopause, the amount of estrogen produced by the female body decreases. This can cause symptoms such as redness of the face, neck and chest ("hot flashes"). Femoston relieves these. symptoms after menopause Femoston should only be prescribed if the symptoms seriously hamper daily life.
Prevent osteoporosis: After menopause some women may develop bone fragility (osteoporosis). You should discuss all available options with your doctor. If you are at high risk of fractures due to osteoporosis and other medicines are not suitable, Femoston can be used. to prevent osteoporosis after menopause.
Contraindications When Femoston is not to be used
Medical history and regular checkups
The use of HRT carries risks that need to be considered when deciding whether to initiate or continue treatment.
There is limited experience in women treated with premature menopause (due to ovarian damage or surgery). In the case of early menopause the risks of treatment with HRT may be different. Talk to your doctor.
Before starting HRT (or restarting), your doctor will ask you about your personal and family medical history. Your doctor may have a breast and / or pelvic (lower abdomen) checkup if necessary.
Once HRT has started, regular medical check-ups (at least annually) still need to be done for an accurate assessment of the risks and benefits of continuing therapy.
Get regular breast checks as recommended by your doctor.
Do not use Femoston if you are in any of the following conditions. If you are unsure about any of the points below, tell your doctor before starting Femoston therapy.
Do not use Femoston:
- if you have, have ever had or are suspected of having breast cancer
- if you have or suspect that you have a tumor whose growth is sensitive to estrogen, for example in the endometrium (lining of the uterus)
- if you have vaginal bleeding of unknown origin
- if you have excessive thickening of the lining of the womb (endometrial hyperplasia) that has not been treated
- if you have or have been treated in the past for blood clots in the veins (thrombosis), such as in the legs (deep vein thrombosis), or in the lungs (pulmonary embolism)
- if you have diseases caused by blood clots (such as protein C, protein S, or antithrombin deficiency)
- if you have or have ever had diseases caused by blood clots in the arteries, such as myocardial infarction, stroke or angina (severe chest pain)
- if you have or have had liver disease in the past and your liver function tests have not returned to normal
- if you have porphyria (inherited metabolic disease due to an alteration in the metabolism of blood pigments)
- if you are allergic (hypersensitive) to estradiol, dydrogesterone or any of the other ingredients of this medicine. During treatment with Femoston, if any of the above conditions appear for the first time, stop taking it and consult your doctor immediately. doctor.
Precautions for use What you need to know before taking Femoston
Tell your doctor or pharmacist before taking Femoston, if you have had any of the following problems in the past, as they may come back or get worse during treatment with Femoston. If so, your doctor may request more frequent checkups:
- uterine fibroids
- growth of the uterine wall outside the uterus (endometriosis) or previous excessive thickening of the uterine wall (endometrial hyperplasia)
- brain tumor which may be related to progesterone levels (meningioma)
- increased risk of developing blood clots (see "Blood clots inside the veins (thrombosis)")
- increased risk of having a tumor whose growth is sensitive to estrogen (having a first degree relative, such as a mother, sister or grandmother, who has had breast cancer)
- hypertension (high blood pressure)
- liver disorders such as benign liver tumor
- diabetes
- gallbladder stones
- migraines or severe headaches
- systemic lupus erythematosus (autoimmune disease)
- epilepsy
- asthma
- otosclerosis (hereditary middle ear disease)
- hypertriglyceridaemia (high increase in blood triglycerides
- fluid retention due to heart or kidney failure.
Stop taking Femoston and consult your doctor immediately
If you notice any of the following when starting HRT:
- one of the conditions mentioned in the paragraph "Do not use Femoston"
- yellowing of the skin or whites of the eyes (jaundice). These can be signs of liver disease
- increased blood pressure (symptoms may be headache, tiredness, dizziness)
- migraine headache appearing for the first time
- if you are pregnant
- if you notice signs of blood clots such as:
- painful swelling and redness of the legs
- sudden pain in the chest
- difficulty in breathing
For more information, see the section "Thrombus within the veins (thrombosis)".
Note: Femoston is not a contraceptive. If you are under the age of 50 or if your last period was less than 12 months ago, you may need additional contraception to prevent pregnancy. Consult your doctor.
HRT and cancer
Excessive thickening of the uterine wall (endometrial hyperplasia) and cancer of the uterine wall (endometrial cancer)
Taking estrogen-only HRT may increase your risk of excessive thickening of the womb (endometrial hyperplasia) and cancer of the womb (endometrial cancer).
The progesterone contained in Femoston prevents this additional risk.
Irregular bleeding
During the first 3-6 months of Femoston therapy you may have irregular bleeding or spotting (drops of blood). However, contact your doctor as soon as possible if irregular bleeding:
- occurs for more than 6 months
- starts after you have been taking Femoston for more than 6 months
- occurs after cessation of therapy with Femoston Breast cancer
Evidence suggests that the risk of breast cancer increases with combined estrogen-progestogen and possibly estrogen-only HRT. The additional risk depends on how long HRT is taken and becomes evident within a few years. However, it returns to normal levels within a few (at most 5) years of stopping therapy.
Data in comparison
Among women aged 50 to 79 who do not use HRT for more than 5 years, an average of 9 to 17 breast cancers per 1,000 women are diagnosed.
Among women aged 50 to 79 who have been using estrogen-progestogen HRT for over 5 years, there will be 13 to 23 cases of breast cancer diagnosed per 1,000 users (4 to 6 additional cases).
Check your breasts regularly. See your doctor if you have any breast changes such as:
- small depressions in the skin
- changes in the nipple
- any visible or perceptible hardening.
Also, participate in mammography follow-up programs when they are offered to you. For mammography check-ups, it is important that you inform the healthcare professional who is taking the x-rays that you are taking HRT, as this medicine can increase breast density affecting the mammogram result. is increased, mammography may not detect all indurations.
Cancer of the ovary
Ovarian cancer is rare - much rarer than breast cancer. Use of estrogen-only or estrogen-progestogen therapy has been associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer varies by age. For example, in women aged 50 to 54 who are not taking HRT, about 2 in 2,000 women will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be around 3 cases in 2,000 women treated (i.e. around 1 more case).
Effects of HRT on the heart and circulation
Blood clots within the veins (thrombosis) The risk of blood clots within the veins is approximately 1.3 - 3 times higher in HRT users, especially during the first year of taking.
Blood clots can be serious, and if one reaches the lungs, it can cause chest pain, breathlessness, fainting, and even death.
As you age, you are more likely to get blood clots in your veins and if you have any of the following, talk to your doctor:
- if you have to be immobilized for a long time due to major surgery, trauma or illness (if you need surgery)
- if you are severely obese (body mass index> 30 kg / m2)
- if you have clotting problems that require prolonged treatment with anticoagulants
- if any of your first degree family members have had blood clots in the leg, lung or other organ in the past
- if you have a rare condition such as systemic lupus erythematosus (SLE)
- if you have cancer
For symptoms of a thrombus, see "Stop taking Femoston and see your doctor immediately".
Data in comparison
In women around the age of 50 who have not taken HRT for more than 5 years, an average of 4 to 7 in 1,000 women can expect to have a venous thrombus.
In women around the age of 50 who have taken estrogen-progestogen HRT for more than 5 years, there will be 9 to 12 cases in 1,000 (e.g. 5 additional cases).
Heart disease (heart attack)
There is no evidence that HRT prevents a heart attack. Women over 60 who are using estrogen-progestogen HRT are slightly more prone to developing heart disease than women who are not taking any HRT.
Stroke
The risk of having a stroke is about 1.5 times higher in HRT users than in non-users. The number of additional cases of stroke due to HRT use may increase with advancing age.
Data in comparison
In women around the age of 50 who have not taken HRT for more than 5 years, an average of 8 in 1,000 women can expect to have a stroke.
In women around the age of 50 who have been taking HRT for over 5 years, there will be 11 in 1,000 cases (e.g. 3 additional cases).
Other conditions
HRT does not prevent memory loss. There is some evidence of a higher risk of memory loss in women starting HRT after the age of 65. Ask your doctor for advice.
Tell your doctor if you have or have had any of the following medical conditions as they will need to check you more frequently:
- heart disease
- kidney failure
- higher than normal levels of some blood fats (hypertriglyceridaemia).
Children
Femoston is not intended for use in children.
Interactions What medications or foods can change the effect of Femoston
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Some medications can interfere with the effectiveness of Femoston. This can lead to irregular bleeding and occurs with the following medications:
- drugs for epilepsy (eg phenobarbital, carbamazepine, phenytoin)
- drugs for tuberculosis (e.g. rifampicin, rifabutin)
- drugs for HIV infection [AIDS] (eg ritonavir, nelfinavir, nevirapine, efavirenz)
- herbal preparations containing St. John's wort (Hypericum perforatum).
Laboratory analysis
If you need to have a blood test, tell your doctor or nurse that you are taking Femoston because this drug can interfere with the results of some tests.
Femoston with food and drink
Femoston can be given with or without food.
Warnings It is important to know that:
Pregnancy and breastfeeding
Femoston is indicated for postmenopausal women only.
If you become pregnant,
- stop taking Femoston and consult your doctor.
Femoston is not indicated during lactation.
Driving and using machines
The effect of Femoston on driving or using machines has not been studied. An effect is unlikely.
Femoston tablets contain lactose
If you are intolerant to some sugars, contact your doctor before taking this drug.
Dose, Method and Time of Administration How to use Femoston: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
When to start Femoston treatment
Do not start Femoston treatment until at least 12 months after your last menstruation.
You can start taking Femoston any day if:
- you are not currently taking any HRT
- you are changing from continuous combined HRT. That is when you take a tablet or patch every day that contains both, an estrogen and a progestin.
Start taking Femoston the day after you finish day 28 of your cycle if:
- you are changing from cyclic or sequential TOS.That is when you take a tablet or use a patch that contains estrogen for the first part of your cycle. Then take a tablet or use a patch containing both an estrogen and a progestin for up to 14 days.
Taking the drug
- swallow the tablet with water
- you can take the tablet with or without food
- try to take the tablet at the same time each day. This will ensure that there is a constant amount of product in your body. It will also help you remember to take the tablet
- take one tablet every day, without interruption between one pack and the next. The days of the week are highlighted on the blisters. This will make it easier for you to remember when to take the tablet.
How long
- your doctor will prescribe the lowest dose to treat your symptoms for as short a time as possible. If you have the impression that this dose is too strong or too low, consult your doctor.
- If you are taking Femoston to prevent osteoporosis, your doctor will adjust your dose. It will depend on your bone mass.
- Take one salmon tablet every day for a 28 day cycle.
If you need surgery
If you need to have surgery, tell your doctor that you are taking Femoston. You may need to stop taking Femoston about 4 - 6 weeks before surgery to reduce the risk of blood clots (blood clots in the veins). Ask your doctor when you can restart Femoston.
If you forget to take Femoston
Take the forgotten tablet as soon as you remember. If it has been more than 12 hours after you were supposed to take the tablet, take your next dose at the usual time. Do not take the missed dose. Do not double the dose. If you miss a dose, irregular bleeding or spotting may occur.
If you stop taking Femoston
Do not discontinue Femoston without the advice of the treating physician.
- If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken an overdose of Femoston
If you have taken too many Femoston tablets (or someone else has) they are unlikely to harm you. You may feel nauseous, or feel sick (vomit), you may have breast pain / tenderness, dizziness, abdominal pain, sleepiness / fatigue, or breakthrough bleeding.
No treatment is needed, but if you are concerned, contact your doctor for advice.
Side Effects What are the side effects of Femoston
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following disorders occur more often in women who use HRT than in women who are not:
- breast cancer
- abnormal growth or cancer of the uterine walls (endometrial hyperplasia or cancer)
- ovarian cancer
- blood clots in the veins of the legs or lungs (venous thromboembolism)
- heart disease
- stroke
- possible memory loss if HRT is started after the age of 65.
The following side effects may occur with this medicine:
Very common (may affect more than 1 in 10 patients treated):
- headache
- abdominal pain
- back pain
- breast pain / tenderness
Common (may affect up to 1 in 10 patients treated):
- vaginal candidiasis (infection caused by a fungus called Candida albicans)
- feeling depressed, nervousness
- migraine. If you are experiencing migraine headache for the first time, stop using Femoston and contact your doctor immediately.
- dizziness
- feeling sick (nausea), vomiting, bloating (swelling of the abdomen), including wind (flatulence)
- allergic skin reactions (rash, severe itching or hives)
- menstrual disorders such as irregular bleeding, spotting, painful periods (dysmenorrhea), heavy or light bleeding
- pelvic pain
- vaginal discharge
- feeling weak, tired or sick
- swelling of the ankles, feet or fingers (peripheral edema)
- weight gain.
Uncommon (may affect up to 1 in 100 patients treated):
- disorders that mimic cystitis
- increase in size of uterine fibroids
- hypersensitivity reactions such as dyspnoea (allergic asthma)
- changes in sexual desire
- blood clots in the veins of the legs and lungs (venous thromboembolism or pulmonary embolism)
- increased blood pressure (hypertension)
- circulation problems (peripheral vascular disease)
- enlarged and tortuous (varicose) veins
- indigestion
- changes in liver function, sometimes with yellowing of the skin (jaundice), feeling faint (asthenia) or generally feeling sick (malaise) and abdominal pain. If you notice yellowing of your skin or whites of your eyes, stop taking Femoston and contact your doctor immediately.
- pathology of the gallbladder
- breast swelling
- symptoms simulating PMS
- weight decrease
Rare (may affect up to 1 in 1,000 patients treated):
(* post-marketing undesirable effects not observed in clinical studies to which the frequency "rare" was attributed)
- disease characterized by the destruction of red blood cells (haemolytic anemia) *
- meningioma (brain tumor) *
- modification of the surface of the eye (increased curvature of the cornea) *, which does not allow contact lenses to be worn (intolerance to contact lenses) *
- heart attack (myocardial infarction)
- stroke *
- swelling of the skin of the face and throat. This can cause difficulty in breathing (angioedema)
- purple spots or dots on the skin (vascular purpura)
- painful reddish skin nodules (erythema nodosum) *, discoloration of the skin especially of the face or neck, known as "pregnancy spots" (chloasma or melasma) *
- leg cramps *
The following side effects have been associated with the use of other HRTs:
- estrogen dependent tumors (both benign and malignant), such as cancer of the uterine walls, ovarian cancer
- increase in the size of progestogen dependent tumors (such as meningioma)
- immune system disease affecting many organs of the body (systemic lupus erythematosus)
- possible dementia
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at www.agenziafarmaco.it/it/responsabili.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use the medicine after the expiry date indicated on the blister and carton. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other Information
What Femoston contains
- The active ingredients are estradiol as well as estradiol hemihydrate and didrogesterone
- each tablet contains 1 mg of estradiol and 5 mg of didrogesterone
- The other ingredients in the tablet core are lactose monohydrate, hypromellose, maize starch, colloidal anhydrous silica and magnesium stearate.
- The other ingredients of the tablet coating are:
- titanium dioxide (E171), yellow iron oxide (E 172), red iron oxide (E 172), hypromellose, macrogol 400.
What Femoston looks like and contents of the pack
- This medicine consists of a film-coated tablet. The tablet is round, biconvex, salmon colored, and marked "379" on one side (7 mm).
- Each blister contains 28 tablets.
- The tablets are packed in PVC / aluminum blisters.
- Packs contain 28, 84 or 280 (10 x 28) film-coated tablets in blisters.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
FEMOSTON 1/5 CONTI TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
28 tablets, each containing 1 mg of 17? -Estradiol (as hemihydrate) and 5 mg of didrogesterone.
Excipient with known effect: lactose monohydrate 114.7mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
Salmon colored, round, biconvex, 1/5 mg tablet, debossed with "379" on one side (size 7 mm).
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Hormone replacement therapy (HRT) for the treatment of estrogen deficiency symptoms in postmenopausal women for more than 12 months.
Prevention of osteoporosis in postmenopausal women at high risk of future fractures who have intolerances or contraindications to other drugs authorized for the prevention of osteoporosis (see also section 4.4).
Experience with the treatment of women over the age of 65 is limited.
04.2 Posology and method of administration
Femoston 1/5 conti is oral HRT to be taken on a continuous combined schedule.
Estrogen and progesterone must be taken every day without interruption.
The dose is one tablet per day for a 28 day cycle.
Femoston 1/5 conti should be taken continuously without interruption between packs.
To initiate and continue treatment of postmenopausal symptoms, the lowest effective dose should be used for as short a period as possible (see also section 4.4).
Continuous combined treatment can be started with Femoston 1/5 count depending on when menopause started and the severity of symptoms. Physiologically menopausal women should start Femoston 1/5 count 12 months after their last menstruation. When menopause is surgically induced, treatment can begin immediately.
In relation to the clinical response, the dosage can subsequently be adjusted on an individual basis.
Patients being treated with a continuous cyclic or sequential regimen must complete the 28-day course of therapy and then initiate Femoston 1/5 count.
Patients from another continuous combination therapy can start treatment at any time.
If a dose is forgotten, the forgotten tablet should be taken as soon as possible. If more than 12 hours have already passed, the next dose should be continued without taking the forgotten tablet. The likelihood of inter-cycle bleeding or spotting may be increased.
Femoston 1/5 conti can be given regardless of food intake.
Pediatric population:
There are no relevant indications for the use of Femoston 1/5 count in the pediatric population.
04.3 Contraindications
- Known, past or suspected breast cancer
- Known or suspected estrogen-dependent neoplasms (eg endometrial cancer)
- Genital bleeding of unknown origin
- Untreated endometrial hyperplasia
- Previous or current venous thromboembolism (deep vein thrombosis, pulmonary embolism)
- Known thrombophilic disorders (e.g. protein C, protein S or antithrombin deficiency, see section 4.4)
- Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
- Acute liver disease or history of liver disease, if liver function indices have not normalized
- Porphyria
- Known hypersensitivity to the active substances or to any of the excipients listed in section 6.1
04.4 Special warnings and appropriate precautions for use
For the treatment of postmenopausal symptoms, HRT should only be initiated in the presence of symptoms that adversely affect quality of life. In any case, an accurate assessment of the risks and benefits must be carried out at least every year and therapy must continue only if the benefits outweigh the risks.
There is limited evidence regarding the risks associated with HRT in the treatment of early menopause. However, due to the low level of absolute risk in younger women, the balance of risks and benefits for these women may be more favorable than in older women.
Medical examination / check-ups
Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical examination (including pelvic and breast) and evaluation of contraindications and warnings for use of HRT will be conducted on this basis. During treatment, periodic check-ups are recommended with frequency and characteristics adapted to the individual needs of the woman. Patients should be advised to report any changes in their breasts to their doctor or healthcare professional (see "Breast cancer" below). furthermore, to carry out an accurate monitoring of the breast, including an appropriate diagnosis by image, eg a mammogram, in accordance with the control programs currently in use, modified according to the individual clinical needs.
Conditions that require supervision
The patient should be carefully monitored if one of the following conditions develops, has occurred in the past, and / or worsened during pregnancy or during previous hormonal treatments. The possibility that these conditions may recur or worsen during treatment with Femoston 1/5 conti should be considered, in particular:
- Leiomyomas (uterine fibroids) or endometriosis
- Risk factors for thromboembolic disorders (see below)
- Risk factors for estrogen-dependent cancers, eg. 1st degree heredity for breast cancer
- Hypertension
- Liver disease (e.g. liver adenomas)
- Diabetes mellitus with or without vascular compromise
- Cholelithiasis
- Migraine or headache (severe)
- Systemic lupus erythematosus
- History of endometrial hyperplasia (see below)
- Epilepsy
- Asthma
- Otosclerosis
- Meningioma
Reasons for immediate discontinuation of therapy:
Therapy should be discontinued if a contraindication appears and in the following situations:
- Jaundice or deterioration of liver function
- Significant increase in blood pressure
- Onset of migraine-like headache
- Pregnancy
Endometrial hyperplasia and carcinoma
• The risk of endometrial hyperplasia and carcinoma in patients with an intact uterus increases when estrogen is administered alone for prolonged periods. The observed increase in the risk of endometrial cancer among estrogen-only users varies from 2 to 12 times more than in women who do not use it, depending on the duration of treatment and the estrogen dosage (see section 4.8 Undesirable effects) . After discontinuation of treatment the risk remains high for at least 10 years.
• The addition of a progestogen administered cyclically for at least 12 days per month over a 28-day cycle or continuous estrogen-progesticin combination therapy in non-hysterectomised patients may prevent the excessive risk associated with estrogen-only HRT.
• Intercycle bleeding and spotting may occur during the first courses of treatment. If these inter-cycle bleeding or spotting appear after a certain period of time from the start of therapy or continue after the interruption of treatment, the cause should be investigated, also using endometrial biopsy to rule out endometrial neoplasms.
Breast cancer
General evidence suggests an increased risk of breast cancer in patients taking combined estrogen-progestogen and possibly estrogen-only HRT, which depends on the duration of treatment with HRT.
Combined estrogen-progestogen therapy:
• The randomized, placebo-controlled study, "Women" s Health Initiative study "(WHI), and epidemiological studies, agree in the finding of an increased risk of breast cancer diagnosis in women on combined estrogen-based HRT. and progestogens which appears after about 3 years (see section 4.8).
Estrogen-only therapy:
• The WHI study showed that the risk of breast cancer in hysterectomised women taking estrogen-only HRT does not increase. Observational studies have mostly reported a slightly increased risk of a breast cancer diagnosis that is substantially lower than that seen in users of combined estrogen-progestogen therapies (see section 4.8).
The excess risk appears within a few years from the start of treatment but returns to its initial value within a few years (at most 5) after the suspension of treatment.
HRT, especially estrogen-progestogen treatment, increases mammography density which may adversely affect the radiological diagnosis of breast cancer.
Ovarian cancer
Ovarian cancer is rarer than breast cancer. Long-term use (at least 5-10 years) of estrogen-only HRT has been associated with a slightly increased risk of ovarian cancer (see section 4.8). Some studies, including the WHI study, suggest that "Long-term use of combined HRT may confer a similar or slightly lower risk (see section 4.8).
Venous thromboembolism
• HRT is associated with a 1.3 to 3-fold risk of developing venous thromboembolism (VTE), eg. deep vein thrombosis or pulmonary embolism. The likelihood of this occurring is higher in the first year of HRT than thereafter (see section 4.8).
• Patients with known thrombophilic states have an increased risk of VTE and HRT may increase this risk. HRT is therefore contraindicated in these patients (see section 4.3).
• Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (body mass index> 30 kg / m2), pregnancy / postpartum period, lupus erythematosus systemic (SLE), and cancer There is no consensus on the possible role of varicose veins in VTE.
As in all post-operative patients, careful attention should be given to prophylactic measures to prevent post-surgical VTE. When prolonged immobilization follows major surgery, temporary discontinuation of HRT is recommended to a period of 4-6 weeks before surgery. Treatment can be resumed after complete mobilization of the patient.
• In patients without a personal history of VTE but with a first degree relative with a previous thrombosis at a young age, controls should be proposed after careful consultation regarding their limits (only part of the problems due to thrombophilia can be identified by the controls ).
If a thrombophilic defect isolated with thrombosis is identified in family members, or if the problem is severe (e.g. antithrombin, protein S, or protein C deficiency or a combination of problems), HRT is contraindicated.
• Women already being treated with anticoagulants require a "careful benefit / risk assessment of" HRT use.
• If VTE occurs after initiation of therapy, the drug should be discontinued. Patients should be advised to contact their physician immediately if they experience potential symptoms of thromboembolism (eg, sore leg edema, sudden chest pain, dyspnea).
Coronary artery disease (CAD)
There is no evidence from randomized controlled trials of protection against myocardial infarction in women with or without coronary disease receiving combined estrogen-progestogen or estrogen-only HRT.
Combined estrogen-progestogen therapy:
The relative risk of CAD during use of combined estrogen-progestogen HRT is slightly increased. The absolute risk at baseline CAD is highly age-dependent, the number of additional cases of CAD due to the use of estrogen -Progestin is very low in healthy women near menopause, but increases with advancing age.
Estrogen-only therapy:
Data from randomized controlled clinical trials do not show an increased risk of CAD in hysterectomised patients treated with estrogen-only therapy.
Ischemic stroke
Combined estrogen-progestogen and estrogen-only therapy are associated with an up to 1.5-fold increased risk of ischemic stroke. The relative risk does not change with age or when menopause is reached. However, as the risk of stroke at initial levels is highly age-dependent, the overall risk of stroke in patients taking HRT increases. with advancing age (see section 4.8).
Other conditions
- Estrogen can cause fluid retention and therefore patients with cardiac or renal dysfunction should be carefully monitored.
- Women with hypertriglyceridaemia should be closely monitored during estrogen replacement or hormone replacement therapy, as rare cases of elevated triglyceride levels leading to pancreatitis have been reported during estrogen therapy.
- Estrogens cause an increase in thyroid hormone binding globulin (TBG), leading to an increase in total thyroid hormone, measured with iodine binding protein (PBI), in T4 levels (on the spine or with radio-immunological method) or T3 levels (with radio-immunological method). Resin uptake of T3 is reduced, reflecting the increase in TBG. The concentrations of free T4 and free T3 are not modified. Other binding proteins may be increased in serum, e.g. corticoid hormone binding globulin (CBG), sex hormone binding globulin (SHBG), causing increased circulating corticosteroids and sex steroids, respectively. The concentration of free or biologically active hormones is not modified. Other plasma proteins may be increased (angiotensinogen / renin substrate, alpha-1-antitrypsin, ceruloplasmin).
HRT does not improve cognitive function. There is some evidence of an increased risk of probable dementia in women who have started continuous combined or estrogen-only HRT after the age of 65.
- Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.
- This combined estrogen-progestogen treatment is not a contraceptive.
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed.
The efficacy of estrogen and progestogen can be reduced:
- The metabolism of estrogens and progestogens may be increased by the concomitant use of substances capable of inducing drug metabolising enzymes, in particular cytochrome P450 enzymes, such as anticonvulsants (eg phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
- Ritonavir and nelfinavir, although known as potent inhibitors, on the contrary they show
inducing properties, when used concomitantly with steroid hormones.
- Herbal preparations containing St. John's wort (Hypericum perforatum)
they can increase the metabolism of estrogens and progestogens.
- From a clinical point of view, the increased metabolism of estrogens and progestogens may lead to a reduction in their effect and changes in the uterine bleeding profile.
04.6 Pregnancy and breastfeeding
Pregnancy
Femoston 1/5 conti is not indicated in pregnancy. If pregnancy occurs during the administration of Femoston 1/5 count, treatment should be stopped immediately.
There are no adequate data on the use of estradiol / dydrogesterone in pregnant women. The results of most epidemiological studies relating to unintentional fetal exposure to combined estrogens and progestogens indicate no teratogenic or foetotoxic effects.
Feeding time
Femoston 1/5 conti is not indicated during lactation.
Fertility
Femoston 1/5 conti is not indicated during the fertile period.
04.7 Effects on ability to drive and use machines
Femoston 1/5 conti does not affect the ability to drive and / or use machines.
04.8 Undesirable effects
The most common side effects seen in patients treated with estradiol / didrogesterone during clinical trials are: headache, abdominal pain, breast pain / tenderness and back pain.
In clinical trials (n = 4929) the following undesirable effects were observed with a frequency listed below: * Undesirable effects reported from spontaneous reports not observed in clinical trials were attributed with the frequency "rare":
Breast cancer risk
• An up to 2-fold increased risk of breast cancer has been reported in patients taking combined estrogen / progestogen HRT for more than 5 years.
• Any increased risk in users of estrogen-only therapy is substantially lower than reported in users of an estrogen-progestogen combination.
• The level of risk is dependent on the duration of therapy (see section 4.4).
• The results of the largest randomized placebo-controlled study (WHI study) and the largest epidemiological study (MWS study) are presented below.
MWS - Estimated Additional Risks of Breast Cancer After 5 Years of Therapy
US WHI Studies - Additional risk of breast cancer after 5 years of therapy
Endometrial cancer risk
Women with a postmenopausal uterus:
The risk of endometrial cancer is about 5 in 1000 women with a uterus who are not using HRT.
In women with a uterus, the use of estrogen-only HRT is not recommended because it increases the risk of endometrial cancer (see section 4.4). Depending on the duration of estrogen-only treatment and the dose of estrogen used, the increased risk of endometrial cancer in epidemiological studies ranged from 5 to 55 additional cases diagnosed per 1000 women aged 50 to 65 years.
Adding a progestogen to estrogen-only therapy for at least 12 days per cycle may prevent the increased risk. In the MWS study, the use of a combination therapy (sequential or continuous) for 5 years does not increase the risk of endometrial cancer (RR of 1.0 (0.8 - 1.2)).
Ovarian cancer
Long-term use of estrogen-only and combined estrogen-progestagen HRT was associated with a slightly increased risk of ovarian cancer. 1 additional case was reported in the 5-year MWS study of HRT. out of 2500 users.
Risk of venous thromboembolism
HRT is associated with a 1.3 to 3-fold increased risk of developing venous thromboembolism (VTE), e.g. deep vein thrombosis or pulmonary embolism. This type of event occurs most during the first year of using HRT (see section 4.4). The following are the results of the WHI studies:
WHI Studies - Additional risk of VTE after more than 5 years of therapy
Coronary heart disease risk
The risk of coronary artery disease is slightly increased in patients on combined estrogen-progestagen HRT who are over 60 years of age (see section 4.4).
Risk of ischemic stroke
The use of estrogen-only and estrogen-progestagen therapy is associated with an up to 1.5-fold greater relative increase in the risk of ischemic stroke. The risk of haemorrhagic stroke is not increased during HRT treatment.
This relative risk is not age-dependent or duration of therapy, but as the baseline risk is highly age-dependent, the overall risk of stroke in women using HRT may increase with age (see section 4.4).
WHI studies combined - Additional risk of ischemic stroke after more than 5 years of therapy
Other adverse reactions have been reported in relation to estrogen-progestogen treatment
Neoplasms benign, malignant and of an unspecified nature:
Both benign and malignant estrogen-dependent neoplasms, eg. endometrial cancer, ovarian cancer. Increase in the size of the meningioma.
Disorders of the immune system:
Systemic lupus erythematosus.
Metabolism and nutrition disorders:
Hypertriglyceridemia.
Nervous system disorders:
Probable dementia, chorea, exacerbation of epilepsy.
Vascular pathologies:
Arterial thromboembolism.
Gastrointestinal disorders:
Pancreatitis (in women with pre-existing hypertriglyceridaemia).
Skin and subcutaneous tissue disorders:
Erythema multiforme.
Renal and urinary disorders:
Urinary incontinence.
Diseases of the reproductive system and breast:
Variations of the fibrocystic breast, erosion of the uterine cervix.
Congenital, familial and genetic disorders:
Worsening of porphyria.
Diagnostic tests:
Total thyroid hormones increased.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Both estradiol and didrogesterone are substances with low toxicity. Symptoms such as nausea, vomiting, breast tenderness, dizziness, abdominal pain, sleepiness / fatigue and delayed menstruation may occur in the event of an overdose. Treatment is unlikely to be necessary. specific or symptomatic.
Pediatric population:
This information is also applicable in the case of overdose in children.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: urogenital system and sex hormones, progestogens and estrogens, fixed combinations.
The ATC code is G03FA14.
Estradiol
The active ingredient, synthetic 17b-estradiol, is chemically and biologically identical to endogenous human estradiol. It supplements the loss of estrogen production in postmenopausal women and relieves menopausal symptoms. Estrogen prevents bone loss following menopause or ovariectomy.
Didrogesterone
Dydrogesterone is an orally active progestogen which has comparable activity to a parenterally administered progestogen.
Since estrogen promotes endometrial proliferation, administration of estrogen alone increases the risk of endometrial hyperplasia and cancer. The addition of a progestin greatly reduces the estrogen-induced risk of endometrial hyperplasia in non-hysterectomised women.
Information from clinical studies
• Improvement of estrogen deficiency symptoms and bleeding characteristics
• Improvement of menopausal symptoms achieved in the first weeks of treatment.
Amenorrhea (absence of bleeding or spotting) occurs in 88% of women after 10-12 months of treatment.
Bleeding and / or spotting appear in 15% of women during the first three months of treatment and in 12% during the 10th-12th month of treatment.
Prevention of osteoporosis:
Estrogen deficiency in menopause is associated with an increase in bone turnover and a reduction in bone mass. The effect of estrogen on bone mineral density is dose dependent. The protective action is effective as long as treatment is continued. After discontinuation of treatment, bone mass continues to be lost at a rate similar to that of untreated women.
Evidence from the WHI study and meta-analysis studies have shown that current use of HRT, either estrogen-only or combined with a progestin - given to mostly healthy women - reduces the risk of osteoporotic hip fractures HRT may also prevent fractures in women with low bone density and / or a diagnosis of osteoporosis, but the evidence in this case is limited.
After one year of treatment with Femoston 1/5 count, the increase in bone mineral density (BMD) of the lumbar vertebrae is 4.0% ± 3.4 (mean ± SD).
The percentage of women who maintain or increase their BMD in the lumbar area during treatment is 90%.
Femoston 1/5 conti has also shown its effect in hip BMD. The increase after one year is 1.5% ± 4.5 (mean ± SD) for the femoral neck, 3.7% ± 6.0 (mean ± SD) at the level of the trochanter and 2.1% ± 7.2 (mean ± SD) for Ward's triangle. The percentage of women who maintain or increase BMD in the three different hip districts during treatment is 71.66 and 81% respectively.
05.2 Pharmacokinetic properties
Estradiol
• Absorption:
The absorption of estradiol depends on the size of the particles: micronized estradiol is rapidly absorbed from the gastrointestinal tract.
The following table provides the steady-state mean pharmacokinetic values of estradiol (E2), estrone (E1) and estrone sulfate (E1S) for each micronized estradiol dose. The results are expressed as mean (SD):
• Distribution:
Estrogen can be found both unbound and bound. Approximately 98-99% of the estradiol dose is bound to plasma proteins, of which approximately 30-52% to albumin and approximately 46-69% to sex hormone binding globulin (SHBG).
• Biotransformation:
After oral administration, estradiol is extensively metabolised. The main metabolites, unconjugated and conjugated, are estrone and estrone sulfate. These metabolites can contribute to estrogenic activity, both directly and after conversion to estradiol. Estrone sulfate can undergo enterohepatic circulation.
• Elimination:
Through the urine, the main components are the glucuronides of estrone and estradiol. The elimination half-life is between 10-16 hours.
Estrogen is secreted in breast milk.
• Dependence on dose and time:
Following the daily oral administration of Femoston, the estradiol concentration reached a steady state after approximately 5 days.
Generally, steady state concentrations appear to be reached after 8-11 days of treatment.
Didrogesterone
• Absorption:
After oral administration, didrogesterone is rapidly absorbed with a Tmax between 0.5 and 2.5 hours. The absolute bioavailability of didrogesterone (oral dose of 20 mg versus intravenous infusion of 7.8 mg) is 28%.
The following table provides the mean steady-state pharmacokinetic values of didrogesterone (D) and dihydrodhydrogesterone (DHD). The results are expressed as mean (SD):
• Distribution:
After intravenous administration of dydrogesterone the steady-state volume of distribution is approximately 1400L. Dydrogesterone and DHD are more than 90% bound to plasma proteins.
• Biotransformation:
After oral administration, didrogesterone is rapidly metabolised to DHD. Levels of the major active metabolite 20? -Dihydro-didrogesterone (DHD) peak approximately 1.5 hours after administration. Plasma levels of DHD are substantially higher compared with the parent drug. The AUC and Cmax of DHD relative to didrogesterone are in the order of 40 and 25 times, respectively. The mean duration of the elimination half-life of didrogesterone and DHD varies from 5 to 7 and from 14 to 17 hours, respectively. A common feature of all metabolites identified is the retention of the 4,6 diene-3-one configuration. of the original component and the absence of 17? -hydroxylation. This explains the lack of estrogenic and androgenic activity of didrogesterone.
• Elimination:
After oral administration of radiolabelled dydrogesterone, on average 63% of the dose is excreted in urine. Total plasma clearance is 6.4 L / min. Excretion is complete within 72 hours. DHD is present in urine mainly in the form of conjugated glucuronic acid.
• Dependence on dose and time:
Single and multiple pharmacokinetic doses are linear in the oral dose range from 2.5 to 10 mg.
Comparison of single and multiple dose kinetics show that the pharmacokinetics of didrogesterone and DHD did not change as a result of repeat dosing. Steady state was reached after 3 days of treatment.
05.3 Preclinical safety data
There are no preclinical safety data in the reference population relevant to the prescriber in addition to those already described in other sections of the Summary of Product Characteristics (SmPC).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablet core: lactose monohydrate, hypromellose, corn starch, colloidal anhydrous silica, magnesium stearate.
Tablet coat: hypromellose, macrogol 400, titanium dioxide (E171), yellow and red iron oxide (E172).
06.2 Incompatibility
Not applicable.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Packs of 14, 28, 84 (3 blisters of 28) or 280 (10 blisters of 28) tablets in PVC-Aluminum blisters.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
BGP Products S.r.l. - Viale Giorgio Ribotta 11 - 00144 Rome (RM).
08.0 MARKETING AUTHORIZATION NUMBER
033639079- "1/5 conti film-coated tablets" 14 tablets in PVC / AL blister
033639081- "1/5 conti film-coated tablets" 28 tablets in PVC / AL blister
033639093- "1/5 conti film-coated tablets" 280 (10x28) tablets in PVC / AL blister
033639105- "1/5 conti film-coated tablets" 84 (3x28) tablets in PVC / AL blister
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
07/07/01
10.0 DATE OF REVISION OF THE TEXT
June 2016
