FEM 7

Patient Information Leaflet

Warning! Please keep this leaflet. The information on the immediate packaging is in a foreign language.
Fem 7 (FemSete 50)
50 μg/24 h (1.5 mg), transdermal system, patch
Estradiol
Fem 7 and FemSete 50 are different brand names of the same medicine.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible side effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

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 in Fem 7 is 17β-estradiol, a hormone identical to naturally occurring estradiol. Estradiol belongs to the group of sex hormones known as estrogens and is produced mainly by granulosa cells of the ovarian follicle. Smaller amounts of estrogens are produced by the corpus luteum, placenta, and adrenal glands. After menopause (when menstruation has completely ceased), ovarian function stops, and the body produces only a small amount of estradiol. Estrogen deficiency causes various disorders in many women, such as hot flushes, sleep disturbances, atrophy of the endometrium and other tissues of the urogenital tract, and osteoporosis.
Fem 7 is available as a transdermal patch. This means that the estrogen needed by the body is slowly delivered through the skin via an adhesive patch. The estradiol in this patch helps relieve unpleasant menopausal symptoms. It may also be used for the prevention of osteoporosis (reduced bone strength) when a patient cannot take other medications 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 previously had breast cancer (see section below on breast cancer);

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• if the patient currently has or is suspected of having endometrial cancer (endometrium – the mucous lining of 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 mucous lining of the uterus);
• if the patient has unexplained vaginal bleeding;
• if the patient currently has or has previously had venous thrombosis (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 deficiency, protein S deficiency 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
The use of Fem 7 in children is contraindicated.
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), the doctor will perform a detailed medical and family history. A physical examination (including pelvic and breast examination) should take into account the patient’s history as well as contraindications and warnings related to HRT use. During treatment, the 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 used as long as the benefits outweigh the risks.
If the patient notices changes in her breasts suggestive of breast 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 outside the uterus 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;
• 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.

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Reasons for immediate discontinuation of treatment.
Treatment should be immediately stopped 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;
• a significant increase in blood pressure;
• the onset of migraine-type headaches;
• pregnancy;
• swelling of the face, tongue and/or throat and/or difficulty swallowing or urticaria, combined with breathing difficulties, suggesting angioedema.

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

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

Comparison:
Among women with an intact uterus who do not use HRT, endometrial cancer is diagnosed in an average of 5 per 1,000 women aged 50–65.
Among women using HRT with estrogens alone, this number is 2 to 12 times higher, depending on the dose and duration of HRT.
Adding a progestogen 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 previous breast cancer should not use HRT.
Evidence confirms that using hormone replacement therapy (HRT) in the form of combined estrogen and progestogen or 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 developing breast cancer is also higher:

• in patients with a close relative (mother, sister or grandmother) who had breast cancer
• in patients with significant overweight. Page 3 of 11

Comparison:
Among women aged 50 to 54 who do not use HRT, breast cancer will be diagnosed in an average of 13 to 17 per 1,000 women over a 5-year period.
Among 50-year-old women starting 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 50-year-old women starting a 5-year course of estrogen-progestogen 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 per 1,000 women over a 10-year period.
Among 50-year-old women starting 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 50-year-old women starting a 10-year course of estrogen-progestogen HRT, the number of cases will be 48 per 1,000 women (i.e. 21 additional cases).
If the patient notices any changes in her breasts, such as:

• skin dimpling
• changes in the nipples
• any visible or palpable lumps, she should consult her doctor as soon as possible. Blood clots

HRT is associated with an increased risk of venous thromboembolism (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 patients with significant overweight
• in patients with a history of thrombosis
• if thrombosis has occurred in close relatives
• if the patient has had at least one miscarriage
• if the patient has clotting disorders requiring anticoagulant therapy
• in patients immobilized for prolonged periods due to major surgery, trauma or illness
• in patients with the rare condition systemic lupus erythematosus. If any of these conditions apply, the patient should consult her doctor about the possibility of starting HRT.

Comparison:
Among women aged 50 to 59 not using HRT, the number of venous thrombosis cases over 5 years is estimated at 4 to 7 per 1,000 women. Among women aged 50 to 59 using estrogen-progestogen HRT, the number of venous thrombosis 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 thrombosis cases over 5 years will be 5 to 8 per 1,000 women (i.e. 1 additional case).
If the patient experiences:
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• painful swelling of the leg
• sudden chest pain
• difficulty breathing, she should consult her doctor immediately and should not use HRT until approved by the doctor. 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 thrombosis. 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 the possibility of using HRT.
HRT does not support the 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 her doctor immediately and should not use HRT until approved by the doctor. 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 risk factors for stroke or has had a previous stroke, she should consult her doctor about whether she can use HRT.
Comparison:
Among women aged 50 to 59 not using HRT, stroke occurs in an average of 8 per 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 progestogens 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 per 2,000 women over a 5-year period. Among women who have used HRT for 5 years, it will occur in about 3 per 2,000 women (i.e. about 1 additional case).
Other disorders
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Estrogens may cause fluid retention; therefore, patients with heart or kidney dysfunction should be carefully monitored. Patients with severe renal insufficiency 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 monitored during estrogen therapy or other HRT, as rare cases have been reported where 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, perception and attention disorders). There is evidence of an increased risk of dementia in women who start HRT after the age of 65.
Fem 7 and other medicines
The metabolism of estrogens and progestogens may be enhanced when used concomitantly with substances that induce drug-metabolizing enzymes (mainly cytochrome P-450 enzymes), such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine) and antiviral drugs (rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as potent enzyme inhibitors, have enzyme-inducing properties when used concomitantly with steroid hormones.
Herbal products containing St John’s wort (Hypericum perforatum) may stimulate estrogen metabolism.
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 progestogens than on orally administered hormones.
Clinically, accelerated metabolism of estrogens and progestogens may lead to reduced hormonal efficacy and disturbances in the bleeding pattern.
Warning! This also applies to medicines taken recently.
Hormone replacement therapy may affect the action of other medicines:

• antiepileptic drug (lamotrigine), as it may increase the frequency of seizures;
• medicines used to treat hepatitis C virus (HCV) (such as ombitasvir/paritaprevir/ritonavir with or without dasabuvir, or glecaprevir/pibrentasvir), as it may cause increased liver function 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 such HCV combination treatment regimens.

Patients should inform their doctor about all medicines currently or recently taken, as well as any medicines they plan to use. The doctor will provide appropriate advice.
Laboratory tests
If blood tests are required, the patient should inform the doctor or laboratory staff about taking Fem 7, 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 should be discontinued immediately.
Results from most epidemiological studies on accidental fetal exposure to estrogens have not shown harmful effects on the embryo or fetus.
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Breastfeeding
Fem 7 is not indicated for use during breastfeeding.
Driving and operating machinery
No effects of Fem 7 on the ability to drive or operate mechanical equipment have been reported.

3. How to use Fem 7

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

Dosage in adults

• Fem 7 should be used once a week, meaning that a used patch must 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 sufficiently 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 appropriately reduced.
• Fem 7 should be used either cyclically (3 weeks of treatment, 1 week without applying a 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 either not currently using HRT or 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 HRT, 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 completing the previous treatment cycle.
Use of Fem 7 in children is contraindicated.

Instructions for use
The procedure is illustrated in the figures below.
The patch consists of a thin, transparent film in the shape of an octagon, attached to a two-part protective liner.
The octagonal portion of the patch is the actual active patch. The adhesive inner side contains the hormone estradiol, which is continuously released through the skin.
Each Fem 7 patch is individually packaged in a sealed, airtight pouch.
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• Tear open one pouch along the side slits (do not use scissors) and remove the patch. (Fig. 1 and 2).
• The patch should be applied to the skin immediately after removal from the packaging.
• Peel off half of the two-part protective liner. Avoid touching 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, clean, dry, 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 waistline!
• 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 the patch 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 each time.
• 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 patch removal, gently wipe it off with a cream or cosmetic lotion.

How long can Fem 7 be used?
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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, significant overdose of estradiol with Fem 7 is unlikely. Any overdose effects can be immediately reversed by removing the patch.
Symptoms of overdose include breast tenderness, swelling, nausea, and genital bleeding.
In case of overdose, the dose should be appropriately reduced.

Missed dose of Fem 7
Even if the patch change is delayed beyond seven days, it should be replaced as soon as possible. The next patch change should then occur on the originally scheduled day.
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 necessity of continuing 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 reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The possible adverse reactions listed below may occur during hormone therapy in the menopausal period.

Very common adverse reactions (may affect more than 1 in 10 patients):

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

Common adverse reactions (may affect less than 1 in 10 patients):

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

Uncommon adverse reactions (may affect less than 1 in 100 patients):

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

Rare adverse reactions (may affect 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 syndrome, breast enlargement
• Fatigue
• Leiomyomas of the uterus

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

Reporting of adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 reactions helps to provide more information on the safety of this medicine.

5. How to store Fem 7

• Keep the medicine out of the sight and reach of children.
• Store below 30ºC.
• 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 together, then discarded.
• Medicines must not be disposed of via the sewage system 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, glycerol esters of hydrogenated resin acids.
Outer protective layer: poly(ethylene terephthalate) (PET).
Protective liner (to be removed): silicone-coated poly(ethylene terephthalate) (PET).

What Fem 7 looks like and contents of the pack
Fem 7 is an octagonal, transparent, flexible transdermal system, a patch with rounded edges, placed on a removable protective foil larger than the system.

4 transdermal systems, patches, and 12 transdermal systems, patches.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing Authorisation Holder in Portugal, country of export:
Theramex Ireland Limited, 3rd 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:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland

Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland

Marketing Authorisation Number in Portugal, country of export: 2638682
Parallel Import Licence Number: 160/25
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