Fem 7

Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Fem 7 (FemSete 50)
50 μg/24 h (1.5 mg), transdermal system, patch
Estradiolum
Fem 7 and FemSete 50 are different trade names for the same medicinal product.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for possible future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What Fem 7 is and what it is used for
2. Important information before using Fem 7
3. How to use Fem 7
4. Possible side effects
5. How to store Fem 7
6. Contents of the pack and other information

1. What Fem 7 is and what it is used for

Fem 7 is a transdermal system in the form of a patch containing estradiol as the active substance. The estradiol contained in Fem 7 is 17β-estradiol, a hormone identical to natural estradiol. Estradiol is a member of the sex hormone group known as estrogens and is produced mainly by granulosa cells of the ovarian follicle. Smaller amounts of estrogens are produced in the corpus luteum, placenta, and adrenal glands. After menopause (when menstruation has completely ceased), ovarian function ceases and the body produces only small amounts of estradiol. Estrogen deficiency leads in many women to various disorders: hot flushes, sleep disturbances, atrophy of the endometrium and other tissues of the urogenital tract, and osteoporosis.
Fem 7 is available as a transdermal system, a patch. This means that the estrogen needed to compensate for the body's deficiency is slowly delivered through the skin via an adhesive patch. The estradiol contained in this patch relieves the unpleasant symptoms of menopause. It may also be used for the prevention of osteoporosis (reduced bone strength) when a patient cannot take other medicines for this purpose.
Experience with the use of this medicine in women over 65 years of age is limited.
Fem 7 is not a contraceptive.

2. Important information before using Fem 7

When not to use Fem 7

• if the patient is allergic to estradiol or any of the other ingredients of this medicine (listed in section 6);
• if the patient currently has, is suspected of having, or has had breast cancer in the past (see section below on breast cancer);
• if the patient currently has or is suspected of having endometrial cancer (endometrium – the mucous membrane lining the uterus) or any other estrogen-dependent malignant tumour (see sections below on endometrial cancer and ovarian cancer);
• if the patient has untreated endometrial hyperplasia (increased number of cells in the endometrial lining of the uterine cavity);
• if the patient has unexplained vaginal bleeding;
• if the patient currently has or has had venous thromboembolism (deep vein thrombosis) or pulmonary embolism or embolism to other parts of the body (see section below on blood clots);
• if the patient has blood clotting disorders (such as protein C, protein S or antithrombin deficiency);
• if the patient currently has or recently had a heart attack, stroke, or angina pectoris (see section below on heart disease and stroke);
• if the patient has acute liver disease or a history of liver disease until liver function test results return to normal;
• if the patient has porphyria.

Children and adolescents
Fem 7 must not be used in children.
Warnings and precautions
Before starting treatment with Fem 7, discuss this with your doctor, pharmacist, or nurse.
Medical examination / follow-up examinations
Before starting or reinitiating hormone replacement therapy (HRT), your doctor will perform a detailed medical history, including family history. A physical examination (including pelvic and breast examination) should take into account the patient's history and the contraindications and warnings related to HRT use. During treatment, your doctor will perform periodic check-ups, the frequency and type of which should be tailored to the individual patient's needs. HRT should only be continued as long as the benefits outweigh the risks.
If the patient notices changes in the breasts suggestive of lumps (see section "Breast cancer" below), she should inform her doctor, who may refer her for a mammogram.
Conditions requiring special monitoring
If any of the following conditions are present, have occurred previously, and/or have significantly worsened during pregnancy or previous hormone replacement therapy, the patient's health should be closely monitored by a physician. It should be considered that these disorders may recur or worsen during treatment with Fem 7. This particularly applies to the following conditions:

• benign uterine tumours (leiomyomas/uterine fibroids) or endometriosis (presence of endometrial tissue fragments in various locations within the pelvis);
• previous thromboembolic disorders or risk factors for them (see below);
• risk factors for estrogen-dependent cancers, e.g. breast cancer in close relatives;
• arterial hypertension;
• liver diseases (e.g. hepatic adenoma);
• diabetes with or without vascular complications;
• gallstones;
• migraine or (severe) headaches;
• systemic lupus erythematosus (an autoimmune disease);
• previous endometrial hyperplasia (see below);
• epilepsy;
• asthma;
• otosclerosis (a disease affecting the bony labyrinth leading to hearing loss);
• hereditary or acquired angioedema.

Indications for immediate discontinuation of treatment
Treatment must be stopped immediately if any of the conditions listed under "When not to use Fem 7" occur, or if any of the following occur:

• jaundice or worsening of liver function;
• significant increase in blood pressure;
• onset of migraine-type headaches;
• pregnancy;
• swelling of the face, tongue and/or throat and/or difficulty swallowing, or urticaria, especially when associated with breathing difficulties, suggesting angioedema.

Safety of HRT use
In addition to its benefits, HRT is associated with certain risks that the patient should consider before starting or continuing this treatment.
Endometrial cancer (cancer of the uterine lining)
Long-term use of estrogen-only therapy increases the risk of endometrial cancer (cancer of the uterine lining). The addition of a progestagen significantly reduces this risk.

• For women with an intact uterus, the doctor will usually prescribe combined estrogen-progestagen therapy. These substances may be prescribed separately or as a combined preparation within HRT.
• For women who have undergone hysterectomy (removal of the uterus), the doctor will discuss with the patient the safety of using estrogen-only therapy without a progestagen.
• For women who have had a hysterectomy due to endometriosis and who still have residual endometriotic foci, the risk may concern any remaining fragments of endometrial tissue in the body. Therefore, the doctor may prescribe combined estrogen-progestagen HRT. Comparison:

Among women with an intact uterus who do not use HRT, endometrial cancer is diagnosed in an average of 5 out of 1,000 women between the ages of 50 and 65.
Among women using estrogen-only HRT, this number is 2 to 12 times higher, depending on the dose and duration of HRT.
Adding a progestagen to estrogen-only HRT significantly reduces the risk of endometrial cancer.
If the patient experiences intermenstrual bleeding or spotting, this is usually not a cause for concern, especially during the first few months of HRT.
However, if bleeding or spotting:

• persists beyond the first few months,
• occurs for the first time some time after starting HRT,
• continues even after stopping HRT, the patient should inform her doctor. This may indicate thickening of the uterine lining.

Breast cancer
Women with current or past breast cancer should not use HRT.
Evidence confirms that using hormone replacement therapy (HRT), either as a combination of estrogen and progestagen or as estrogen alone, increases the risk of developing breast cancer. The additional risk depends on how long the patient uses HRT. This additional risk becomes apparent after 3 years of HRT use.
After stopping HRT, the additional risk gradually decreases, but may persist for 10 years or longer if HRT was used for more than 5 years.
The risk of breast cancer is also higher:

• in women who have a close relative (mother, sister, or grandmother) with breast cancer;
• in women who are significantly overweight.

Comparison:
Among women aged 50 to 54 who do not use HRT, breast cancer will be diagnosed in an average of 13 to 17 out of 1,000 women over a 5-year period.
Among women aged 50 who start a 5-year course of estrogen-only HRT, the number of cases will be 16–17 per 1,000 women (i.e. 0 to 3 additional cases).
Among women aged 50 who start a 5-year course of combined estrogen-progestagen HRT, the number of cases will be 21 per 1,000 women (i.e. 4 to 8 additional cases).
Among women aged 50 to 59 who do not use HRT, breast cancer will be diagnosed in an average of 27 out of 1,000 women over a 10-year period.
Among women aged 50 who start a 10-year course of estrogen-only HRT, the number of cases will be 34 per 1,000 women (i.e. 7 additional cases).
Among women aged 50 who start a 10-year course of combined estrogen-progestagen HRT, the number of cases will be 48 per 1,000 women (i.e. 21 additional cases).
If the patient notices any changes in the breasts, such as:

• skin dimpling of the breast,
• nipple changes,
• any visible or palpable lumps, she should consult a doctor as soon as possible.

Blood clots
HRT is associated with an increased risk of venous thrombosis (deep vein thrombosis), particularly during the first year of treatment.
These clots are not always life-threatening, but if one travels to the lungs, it may cause chest pain, shortness of breath, collapse, or even death. This condition is known as pulmonary embolism.
Deep vein thrombosis and pulmonary embolism are examples of venous thromboembolic disease (VTE).
The occurrence of blood clots is more likely:

• in women who are significantly overweight;
• in women with a history of blood clots;
• if blood clots have occurred in close relatives;
• if the patient has had at least one miscarriage;
• if the patient has clotting disorders requiring anticoagulant treatment;
• in women immobilized for prolonged periods due to major surgery, trauma, or illness;
• in women with the rare condition systemic lupus erythematosus.

If any of these conditions apply to the patient, she should consult her doctor about whether starting HRT is possible.
Comparison:
Among women aged 50 to 59 who do not use HRT, the estimated number of cases of venous blood clots over 5 years is 4 to 7 per 1,000 women. Among women aged 50 to 59 using combined estrogen-progestagen HRT, the number of venous blood clot cases over 5 years will be 9 to 12 per 1,000 women (i.e. 5 additional cases). Among women aged 50 to 59 who have had a hysterectomy and are using estrogen-only HRT, the number of venous blood clot cases over 5 years will be 5 to 8 per 1,000 women (i.e. 1 additional case).
If the patient experiences:

• painful swelling of the leg,
• sudden chest pain,
• difficulty breathing, she should consult a doctor immediately and must not use HRT until her doctor gives approval. These may be symptoms of thrombosis.

If the patient is scheduled for surgery, she should inform her doctor. It may be necessary to discontinue HRT 4 to 6 weeks before surgery to reduce the risk of clot formation. The doctor will advise when HRT can be resumed.
Ischaemic heart disease
HRT is not recommended for women with current or recent heart disease.
If the patient has ever had heart disease, she should consult her doctor about whether HRT use is possible.
HRT does not support prevention of heart disease.
Studies with one type of HRT (conjugated estrogens and medroxyprogesterone) have shown that the risk of heart disease may be slightly higher during the first year of treatment. For other types of HRT, the risk may be similar, although this is not certain.
If the patient experiences:

• chest pain radiating to the arm and neck, she should consult a doctor immediately and must not use HRT until her doctor gives approval. These may be symptoms of heart disease.

Stroke
Recent studies suggest that HRT slightly increases the risk of stroke. Other factors that may increase stroke risk include:

• ageing;
• high blood pressure;
• smoking;
• alcohol abuse;
• irregular heartbeat.

If the patient has any of the above-mentioned factors increasing stroke risk, or if she has had a stroke in the past, she should consult her doctor about whether she can use HRT.
Comparison:
Among women aged 50 to 59 who do not use HRT, stroke occurs in an average of 8 out of 1,000 women over 5 years. Among women aged 50 to 59 using HRT, the number of stroke cases over 5 years will be 11 per 1,000 women (i.e. 3 additional cases).
Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. The use of HRT containing only estrogens or a combination of estrogens and progestagens is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2,000 women over a 5-year period. Among women who have used HRT for 5 years, it will occur in about 3 out of 2,000 women (i.e. about 1 additional case).
Other disorders
Estrogens may cause fluid retention; therefore, patients with heart or kidney dysfunction should be carefully monitored. Patients with severe renal impairment should be closely monitored, as increased blood concentrations of the active substances in Fem 7 may be expected.
Patients with a history of hypertriglyceridemia should be carefully observed during estrogen therapy or other HRT, as rare cases have been reported in which increased serum triglyceride levels led to pancreatitis during estrogen therapy.
Estrogens affect the levels of other hormones and proteins.
HRT does not improve cognitive function (memory loss, perceptual disturbances, attention deficits). Evidence suggests an increased risk of dementia in women who start HRT after age 65.
Fem 7 and other medicines
The metabolism of estrogens and progestagens may be enhanced when used concomitantly with substances that induce the activity of drug-metabolizing enzymes (mainly cytochrome P-450 enzymes), such as antiepileptic drugs (e.g. phenobarbital, phenytoin, carbamazepine) and antimicrobial agents (rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as strong enzyme inhibitors, may exhibit enzyme-inducing properties when used concomitantly with steroid hormones.
Herbal products containing St John's wort (Hypericum perforatum) may increase the metabolism of estrogens.
With transdermal administration, the so-called "first-pass effect" in the liver does not occur; therefore, enzyme-inducing substances have less impact on transdermally administered estrogens and progestagens than on orally administered hormones.
Clinically, accelerated metabolism of estrogens and progestagens may lead to reduced hormonal efficacy and disturbances in the vaginal bleeding pattern.
Warning! This also applies to medicines taken recently.
Hormone replacement therapy may affect the action of other medicines:

• the antiepileptic drug lamotrigine, as it may increase the frequency of seizures;
• medicines used to treat hepatitis C virus (HCV) (such as the ombitasvir/paritaprevir/ritonavir regimen with or without dasabuvir, or the glecaprevir/pibrentasvir regimen), as it may cause increased liver function test parameters in blood laboratory tests (elevated liver enzyme AlAT activity) in women using combined hormonal contraceptives containing ethinylestradiol. Fem 7 contains estradiol instead of ethinylestradiol. It is not known whether elevated AlAT liver enzyme activity may occur when Fem 7 is used concomitantly with these HCV combination treatment regimens.

The patient should inform her doctor about all medicines currently or recently taken, as well as any medicines she plans to take. The doctor will provide appropriate advice.
Laboratory tests
If blood tests are required, inform the doctor or laboratory staff that Fem 7 is being taken, as this medicine may affect the results of certain tests.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Fem 7 is not indicated during pregnancy. If the patient becomes pregnant while being treated with Fem 7, the medicine must be discontinued immediately.
Results from most epidemiological studies on accidental fetal exposure to estrogens have not shown harmful effects on the embryo or fetus.
Breastfeeding
Fem 7 is not indicated for use during breastfeeding.
Driving and operating machinery
No effects of Fem 7 on the ability to drive motor vehicles or operate mechanical equipment have been reported.

3. How to use Fem 7

This medicine should always be used as directed by your doctor. If in doubt, consult your doctor or pharmacist.

Dosage in adults

• Fem 7 is applied once a week; the used patch should be immediately replaced with a new one every 7 days (always on the same day of the week).
• Treatment should begin by applying one patch.
• If menopausal symptoms are not relieved, the dose may be increased to two patches per week.
• Do not use more than two patches per week.
• If signs of overdose occur, such as breast tenderness, the dose should be reduced accordingly.
• Fem 7 should be used either cyclically (3 weeks of treatment, 1 week without applying the patch) or continuously.
• In women with an intact uterus who are using hormone replacement therapy (HRT), a progestagen must also be administered for at least 12 days of the cycle. After stopping the progestagen, regular withdrawal bleeding may occur.

In women who have had a hysterectomy and who are not currently using hormone replacement therapy, or who are switching from another HRT product, treatment with Fem 7 may be started at any time.
In women with an intact uterus who are not currently using hormone replacement therapy, treatment with Fem 7 may also be started at any time.
In women with an intact uterus who are currently using sequential HRT, treatment with Fem 7 may be started after completion of the previous treatment cycle.
The use of Fem 7 in children is contraindicated.

Method of application
The instructions for use are illustrated in the figures below.
The patch consists of a thin, transparent film in the shape of an octagon, connected to a two-part protective liner.
The octagonal part of the patch is the actual active patch. The inner adhesive side contains the hormone estradiol, which is continuously released into the skin.
Each Fem 7 patch is individually packed in a sealed, airtight pouch.

• Tear open one pouch along the side notches (do not use scissors) and remove the patch. (Fig. 1 and 2).
• Apply the patch to the skin immediately after removing it from the packaging.
• Remove half of the two-part protective liner. Do not touch the adhesive surface of the patch with fingers. Apply the adhesive side of the patch to the skin. (Fig. 3 and 4).
• Remove the second half of the protective liner. Press the patch firmly with the palm of your hand and hold for 30 seconds. The patch will warm to body temperature, ensuring optimal adhesion to the skin. (Fig. 5 and 6). Make sure the entire patch adheres to the skin, especially at the edges.
• The application site should be changed each time; that is, a new patch may be applied to the same site only after two weeks.
• The skin at the chosen site should be healthy, dry, clean, degreased, and undamaged.
• The best sites for applying the patch are the hips, upper buttocks, and lower abdomen, as the skin in these areas is relatively smooth. The Fem 7 patch must not be applied to the breasts or the area immediately surrounding them! Do not apply the patch at the waist!
• The patch adheres strongly to the skin. Bathing, showering, and physical exercise should not affect the patch's performance.
• Avoid rubbing the patch with a sponge or towel, as this may cause it to detach.
• Avoid wearing tight clothing that could cause the patch to peel off.
• If the patch detaches completely before 7 days have passed, simply apply a new patch.
• Each patch should be used for seven days. It is recommended to change the patch on the same day of the week.
• The next patch should be applied according to the original treatment schedule. Avoid exposing the patch to direct sunlight.

If any adhesive residue remains on the skin after removing the patch, gently wipe it off using a cream or cosmetic milk.

How long can Fem 7 be used?
Each patch should be used for seven days.
HRT should be continued only as long as the benefits of relieving menopausal symptoms outweigh the risks associated with HRT use.

Use of a higher than recommended dose of Fem 7
Due to the route of administration, a significant overdose of estradiol with Fem 7 is unlikely, and the effects of overdose can be immediately reversed by removing the patch.
Symptoms of overdose include breast tenderness, swelling, nausea, and vaginal bleeding.
In case of overdose, the dose should be reduced accordingly.

Missed dose of Fem 7
Even if the patch change is delayed beyond seven days, it should be replaced immediately. The next patch change should then occur on the originally scheduled day, at the usual time.
Do not use a double dose to make up for a missed patch.

Stopping treatment with Fem 7
The duration of treatment is determined by the doctor. The need for continued treatment should be reviewed regularly (e.g., every 6 months). If treatment is stopped earlier than planned or if adverse effects occur, consult your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone experiences them.
Below are listed possible adverse effects associated with hormone therapy during the menopausal period.

Very common adverse effects (may occur in more than 1 in 10 patients):

• Skin reactions at the site of the patch application, including itching, redness of the skin (erythema), rash, urticaria, skin swelling, and skin pigmentation changes. These reactions usually resolve within 2–3 days after removing the patch.

Common adverse effects (may occur in less than 1 in 10 patients):

• Increase or decrease in body weight
• Headache
• Abdominal pain, nausea
• Skin rash, itching
• Bleeding or spotting from the uterus or vagina

Uncommon adverse effects (may occur in less than 1 in 100 patients):

• Hypersensitivity reaction
• Depressive mood
• Visual disturbances
• Palpitations
• Nodular erythema, urticaria
• Breast pain, breast tenderness
• Dizziness
• Dyspepsia
• Edema

Rare adverse effects (may occur in less than 1 in 1,000 patients):

• Nervousness
• Decreased or increased libido
• Migraine
• Intolerance to contact lenses
• Bloating and vomiting
• Hirsutism, acne
• Muscle cramps
• Painful menstruation, vaginal discharge, premenstrual tension syndrome, breast enlargement
• Fatigue
• Uterine leiomyomas

If any of these symptoms occur, inform your doctor, who will adjust the dosage of the medicine.

Reporting of adverse effects

If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to collect more information on the safety of the medicine.

5. How to store Fem 7

• Keep the medicine out of the sight and reach of children.
• Store below 30°C.
• Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
• Used patches should be folded in half with the adhesive side inwards, then discarded.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Fem 7 contains
The active substance is estradiol (in the form of estradiol hemihydrate).
1 transdermal system, patch, contains:
active substance
estradiol (as estradiol hemihydrate 1.5 mg).
The active surface area of the system is 15 cm².
The release rate of estradiol is 50 μg/24 h over 7 days.
other components are:
Adhesive layer: styrene-isoprene copolymer, glyceryl esters of hydrogenated resin acids.
Outer protective layer: poly(ethylene terephthalate) (PET).
Protective liner (to be removed): poly(ethylene terephthalate) (PET) coated with silicone.

What Fem 7 looks like and contents of the pack
Fem 7 is an octagonal, fully transparent transdermal system, patch. Its inner (adhesive) layer is covered with a two-part transparent protective film.
Available in packs containing 4 transdermal systems, patches, or 12 transdermal systems, patches.
For more detailed information, please contact the marketing authorisation holder or parallel importer.

Marketing authorisation holder in Portugal, country of export:
Theramex Ireland Limited
3 Floor, Kilmore House
Park Lane, Spencer Dock
D01 YE64 - Dublin 1, Ireland

Manufacturer:
LTS Lohmann Therapie-Systeme AG
Lohmannstr. 2
56626 Andernach
Germany

Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Poland

Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Poland

Marketing authorisation number in Portugal, country of export: 2638682
Parallel import authorisation number: 174/24