Fem 7

Leaflet accompanying the packaging: patient information

Fem 7

Estradiol
50 µg/24 h (1.5 mg), transdermal system

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Fem 7 and what is it 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 packaging and other information

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

Fem 7 is a transdermal system containing estradiol as the active substance. The estradiol in Fem 7 is 17β (beta) estradiol, a hormone identical to natural estradiol.
Estradiol belongs to the group of sex hormones, estrogens, and is mainly produced in the granulosa cells of the ovarian follicle. In smaller amounts, estrogens are produced in the corpus luteum, placenta, and adrenal glands. After menopause (when menstruation completely stops), ovarian function decreases, and the body produces only a small amount of estradiol. The lack of estrogens is the cause of various disorders in many women: hot flashes, sleep disturbances, atrophy of the uterine mucosa and other tissues of the urogenital system, and osteoporosis.
Fem 7 is available as a transdermal system. This means that the estrogen that the body needs to supplement is slowly delivered to the body through the skin using an adhesive patch. The estradiol in this patch alleviates the unpleasant symptoms of menopause. It can also be used for the prevention of osteoporosis (reduced bone strength) if the patient cannot take other medications for this purpose.
Experience with the use of the 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 has or is suspected of having breast cancer (see below regarding breast cancer);
• if the patient has or is suspected of having endometrial cancer (endometrium - uterine mucosa) or any other estrogen-dependent malignant tumor (see below regarding endometrial cancer and ovarian cancer);
• if the patient has untreated endometrial hyperplasia (an increase in the number of cells of the uterine mucosa lining its cavity);
• if the patient has vaginal bleeding of unknown cause;
• if the patient has or has had venous thrombosis (deep vein thrombosis) or migrating blood clots to the lungs or other parts of the body (see below regarding blood clots)
• if the patient has blood coagulation disorders(such as protein C, protein S, or antithrombin deficiency);
• if the patient has had a heart attack, stroke, or angina pectoris recently (see below regarding heart disease and stroke);
• if the patient has acute liver disease or has had liver disease in the past, until liver function test results are normalized;
• if the patient has porphyria.

Children and adolescents

The use of Fem 7 in children is contraindicated.

Warnings and precautions

Before starting Fem 7, discuss it with your doctor, pharmacist, or nurse.
Medical examination / control examinations
Before starting or re-establishing hormone replacement therapy, the doctor will conduct a thorough medical interview, including a family history. The physical examination (including examination of the pelvic organs and breasts) should take into account the data from the interview and the contraindications and warnings regarding HRT. During treatment, the doctor will perform periodic control examinations, the frequency and type of which should be adapted to the individual patient's needs. HRT should be used for as long as the benefits of its use outweigh the risks.
If the patient notices changes in her breasts corresponding to breast lumps (see "Breast cancer" below), she should report it to her doctor, who may refer her for a mammogram.
Conditions requiring special monitoring
If any of the following situations or conditions occur, have occurred in the past, or have worsened during pregnancy or previous hormone replacement therapy, the patient's health should be closely monitored by a doctor. It should be considered that the listed disorders may recur or worsen during the use of Fem 7. This applies in particular to diseases such as:

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

Indications for immediate discontinuation of treatment.
Treatment should be discontinued immediately if any of the conditions listed in the "When not to use Fem 7" section occur or if any of the following occur:

• jaundice or worsening of liver function;
• significant increase in blood pressure;
• appearance of migraines;
• pregnancy;
• swelling of the face, tongue, and (or) throat and (or) difficulty swallowing or hives, in combination with difficulty breathing, which suggests angioedema.

Safety of HRT
In addition to the benefits, HRT is associated with certain risks that the patient should consider when deciding on this type of treatment or its continuation.
Endometrial cancer (uterine mucosa cancer)
Long-term administration of estrogens alone increases the risk of endometrial cancer (endometrial cancer). The additional administration of progestogen significantly reduces this risk.

• Patient with an intact uterus is usually prescribed progestogen and estrogen therapy by the doctor. These substances may be prescribed separately or in the form of a combined drug as part of HRT.
• In the case of patients who have had a hysterectomy (removal of the uterus), the doctor will discuss with the patient the safety of using only estrogen without progestogen.
• In the case of patients who have had a hysterectomy due to endometriosis, in whom residual endometriosis foci remain, the risk may apply to any remaining fragments of the uterine mucosa in the body. Therefore, the doctor may prescribe HRT consisting of progestogen and estrogen.

Comparison:
Comparing women with an intact uterus who do not use HRT- in about 5 out of 1,000of them, the doctor will diagnose endometrial cancer between the ages of 50 and 65.
In the case of women using HRT with estrogens only,this number will be 2 to 12 times higher, depending on the dose and duration of HRT.
Adding progestogen to HRT with estrogens only significantly reduces the risk of endometrial cancer.
If the patient experiencesintermenstrual bleeding or spotting, it is usually not a cause for concern, especially during the first few months of HRT use.
If, however, the bleeding or spotting:

• lasts longer than the first few months
• occurs for the first time some time after starting HRT
• persists even after discontinuing HRT, the patient should inform the doctor. This may indicate that the uterine mucosa has thickened.

Breast cancer

Women with current or past breast cancer should not use HRT.

Data confirm that taking hormone replacement therapy (HRT) in the form of combined estrogen and progestogen or estrogen alone increases the risk of 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 will decrease over time, but the risk may persist for 10 years or longer if HRT lasted more than 5 years.
The risk of breast cancer is also higher:

• in patients whose close relatives (mother, sister, or grandmother) had breast cancer
• in patients with significant overweight.

Comparison:
In the case of women between the ages of 50 and 54 who do not use HRT, breast cancer will be diagnosed in about 13 to 17 out of 1,000 women over a period of 5 years.
In the case of women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1,000 patients (i.e., 0 to 3 additional cases).
In the case of women aged 50 who start 5-year estrogen-progestogen HRT, the number of cases will be 21 out of 1,000 patients (i.e., 4 to 8 additional cases).
In the case of women between the ages of 50 and 59 who do not use HRT, breast cancer will be diagnosed in about 27 out of 1,000 women over a period of 10 years.
In the case of women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 out of 1,000 patients (i.e., 7 additional cases).
In the case of women aged 50 who start 10-year estrogen-progestogen HRT, the number of cases will be 48 out of 1,000 patients (i.e., 21 additional cases).
If the patient noticesany changes in the breasts, such as:

• dimples in the breast skin
• changes in the nipples
• any visible or palpable lumps should report to the doctor as soon as possible.

Blood clots
HRT is associated with a higher risk of venous blood clots (deep vein thrombosis), especially in the first year of HRT use.
These blood clots are not always life-threatening if, however, one of them migrates to the lungs, it can cause chest pain, shortness of breath, collapse, or even death. This condition is called pulmonary embolism.
Deep vein thrombosis and pulmonary embolism are examples of venous thromboembolic disease(VTE).
Blood clots are more likely to occur:

• in patients with significant overweight
• in patients with a history of blood clots
• if there have been blood clots in the patient's close family
• if the patient has had at least one miscarriage
• if the patient has coagulation disorders requiring treatment with anticoagulant medications
• in patients who are immobilized for a longer period due to major surgery, injury, or illness
• in patients with a rare disease called systemic lupus erythematosus.

If any of these conditions occur in the patient, they should consult a doctor to determine if it is possible to start HRT.
Comparison:
In women between the ages of 50 and 59 who do not use HRT, the number of blood clot cases over 5 years is estimated to be 4 to 7 out of 1,000 women. In women between the ages of 50 and 59 using estrogen-progestogen HRT, the number of blood clot cases over 5 years will be 9 to 12 out of 1,000 women (i.e., 5 additional cases). In women between the ages of 50 and 59 with a hysterectomy using only estrogen HRT, the number of blood clot cases over 5 years will be 5 to 8 out of 1,000 women (i.e., 1 additional case).
If the patient experiences:

• painful swelling of the leg
• sudden chest pain
• difficulty breathing should report to the doctor as soon as possible and not use HRT until the doctor agrees. These may be symptoms of thrombosis.

If the patient is scheduled for surgery, they should inform the doctor. It may be necessary to discontinue HRT 4 to 6 weeks before surgery to reduce the risk of blood clots. The doctor will inform the patient when they can resume HRT.
Ischemic heart disease
HRT is not recommended for women with current or recent heart disease. If the patient has ever had heart disease, they should consult a doctor to determine if it is possible to use 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.
In the case of other HRTs, it is likely that the risk will be similar, but this is not certain.
If the patient experiences:

• chest pain radiating to the arm and neck should report to the doctor as soon as possible and not use HRT until the doctor agrees. These may be symptoms of heart disease.

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

• aging
• high blood pressure
• smoking
• alcohol abuse
• irregular heartbeat

If the patient has any of the above factors that increase the risk of stroke, or if the patient has had a stroke in the past, they should consult a doctor to determine if they can use HRT.
Comparison:
In women between the ages of 50 and 59 who do not use HRT, stroke will occur in about 8 out of 1,000 women over a period of 5 years. In women between the ages of 50 and 59 using HRT, the number of stroke cases over 5 years will be 11 cases out of 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, in women between the ages of 50 and 54 who do not use HRT, ovarian cancer will be diagnosed over a period of 5 years in about 2 out of 2,000 women. In women who have taken HRT for 5 years, it will occur in about 3 out of 2,000 women using it (i.e., about 1 additional case).
Other disorders
Estrogens can cause fluid retention, so patients with heart or kidney disorders should be closely monitored. Patients with end-stage renal failure should be closely monitored, as the concentration of the active substances of Fem 7 in the bloodstream may increase.
Patients with previously occurring hypertriglyceridemia should be closely monitored during estrogen therapy or other hormone replacement therapy, as rare cases have been reported where increased triglyceride levels in the blood led to pancreatitis when using estrogen therapy.
Estrogens affect the levels of other hormones and proteins.
HRT does not improve cognitive function (memory loss, perception disorders, attention). There is evidence of an increased risk of dementia in women who started HRT at an age over 65.

Fem 7 and other medicines

The metabolism of estrogens and progestogens may be increased during concomitant use of substances that induce the activity of enzymes that metabolize drugs (mainly cytochrome P-450 enzymes), such as antiepileptic drugs (e.g., phenobarbital, phenytoin, carbamazepine) and anti-infective 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 induce estrogen metabolism.
Due to the transdermal route of administration, the "first-pass" effect in the liver does not occur, so inducing substances have less effect on estrogens and progestogens administered in this way than on those taken orally.
Clinically, accelerated metabolism of estrogens and progestogens may lead to a decrease in the effectiveness of these hormones and disturbances in the menstrual bleeding profile.
Warning!This also applies to medications taken recently.
Hormone replacement therapy may affect the action of other medications:

• anti-epileptic drugs (lamotrigine), as it may increase the frequency of seizures;
• drugs used to treat viral hepatitis C (such as the treatment regimen using ombitasvir/paritaprevir/ritonavir with dasabuvir or without dasabuvir and the treatment regimen using glecaprevir/pibrentasvir) as it may cause an increase in liver function test parameters in the blood (increased activity of the liver enzyme ALT) in women using combined hormonal contraceptives containing ethinyl estradiol. Fem 7 contains estradiol instead of ethinyl estradiol. It is not known whether increased liver enzyme ALT activity may occur when using Fem 7 concomitantly with this type of combined hepatitis C treatment regimen.

Tell your doctor about all medications you are currently taking or have recently taken, as well as any medications you plan to take. The doctor will provide you with appropriate instructions.

Lab tests

If a blood test is necessary, inform your doctor or laboratory staff that you are taking Fem 7, as this medication may affect the results of some tests.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before using this medication.
Fem 7 is not indicated for use during pregnancy. If you become pregnant during treatment with Fem 7, discontinue the medication immediately.
Most epidemiological studies to date have not shown adverse effects on the fetus due to accidental exposure to estrogens.
Breastfeeding
Fem 7 is not indicated for use during breastfeeding.

Driving and using machines

No effects of Fem 7 on the ability to drive vehicles or operate machinery have been reported.

3. How to use Fem 7

Always use this medication exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Dosage for adults

• Fem 7 is used once a week, i.e., the used patch should be replaced immediately with a new one every 7 days (always on the same day of the week).
• Treatment should be started with one patch.
• If there is no alleviation of menopausal symptoms, the dose can be increased to two patches per week.
• No more than two patches should be used per week.
• If symptoms of overdose occur, e.g., breast tenderness, the dose should be reduced accordingly.
• Fem 7 should be used cyclically (3 weeks of treatment, 1 week without patching) or continuously.
• In the case of using the Fem 7 patch in women with an intact uterus, a progestogen hormone must also be administered for at least 12 days of the cycle. After completing progestogen intake, regular withdrawal bleeding may occur.

In women who have had a hysterectomy and are not using hormone replacement therapy or are switching from another product to HRT, Fem 7 can be started at any time.
In women with an intact uterus who are not using hormone replacement therapy, Fem 7 can be started at any time.
In women with an intact uterus using sequential HRT, Fem 7 can be started after completing the previous treatment cycle.

The use of Fem 7 in children is contraindicated.

Method of administration
The instructions for handling the patch are illustrated in the following figures.
The patch consists of a thin, transparent foil, hexagonal in shape, connected to a two-part, stronger protective foil.
The hexagonal 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 packaged in a separate, tightly sealed sachet.

• Tear open one of the sachets along the side notches (do not use scissors), and then remove the patch. (Fig. 1 and 2).
• The patch should be applied to the skin immediately after removal from the packaging.
• Remove half of the two-part protective layer. Do not touch the adhesive side of the patch with your fingers. Apply the adhesive side of the patch to the skin. (Fig. 3 and 4).
• Remove the second half of the protective layer. Press the patch with your hand and hold for 30 seconds. The patch will warm up 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 patch application site should be changed each time, i.e., a new patch can be applied to the same site after two weeks.
• The skin at the selected site should be healthy, degreased, dry, and undamaged.
• The best places to apply the patch are the hips, upper buttocks, and lower abdomen, as the skin is relatively smooth in these areas. Fem 7 patches should not be applied to the breasts or their immediate vicinity! Do not apply the patch to the waist!

.

• The patch adheres strongly to the skin. Bathing in a bathtub, showering, and exercising should not affect the patch's action.
• Avoid rubbing the patch with a sponge or towel, as this may cause the patch to peel off.
• Do not wear tight clothing that may cause the patch to peel off.
• If the patch peels off completely before 7 days, simply apply a new patch.
• Each patch should be used for 7 days. It is recommended to change the patch on the same day of the week.
• Apply the next patch according to the original treatment plan. Avoid exposing the patch to direct sunlight. If some adhesive remains on the skin after removing the patch, gently rub it off with a cream or cosmetic milk.

How long can Fem 7 be used

Each patch should be used for 7 days.
HRT should be continued for as long as the benefits of alleviating menopausal symptoms outweigh the risks associated with HRT use.

Using more than the recommended dose of Fem 7

Due to the route of administration, significant overdose of estradiol when using Fem 7 is unlikely, and the effects of overdose can be immediately eliminated by removing the patch.
Symptoms of overdose are mainly: breast tenderness, swelling, nausea, and vaginal bleeding.
In case of overdose, the dose of the medication should be reduced accordingly.

Missing a dose of Fem 7

Also, in the case of missing a patch change after 7 days, it should be replaced immediately, and the next patch change should be done on the scheduled day, at the usual time.
Do not use a double dose to make up for a missed patch.

Stopping Fem 7 treatment

The duration of the entire treatment is determined by the doctor. It is recommended to regularly (e.g., every 6 months) determine whether continued treatment is necessary. In case of early termination of treatment or if side effects occur, consult a doctor.
If you have any further questions about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Fem 7 can cause side effects, although not everybody gets them.
The following side effects are possible during hormone replacement therapy in the menopause period.
Very common side effects (which may occur in more than 1 in 10 patients):

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

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

• weight gain or loss
• headaches,
• abdominal pain, nausea,
• rash, itching,
• vaginal bleeding or spotting

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

• allergic reaction,
• depressive mood,
• vision disorders,
• palpitations,
• erythema nodosum, hives,
• breast pain, breast tenderness,
• dizziness,
• nausea,
• edema,

Rare side effects (which 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, discharge, premenstrual syndrome, breast enlargement,
• fatigue,
• uterine fibroids.

If you experience any of these symptoms, tell your doctor, who will adjust the dosage of the medication.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of this medication.

5. How to store Fem 7

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

6. Contents of the packaging and other information

What Fem 7 contains

The active substance of Fem 7 is estradiol.
1 transdermal system contains:
active substance
1.5 mg estradiol (Estradiolum)hemihydrate
The active surface area of the system is 15 cm².
The estradiol release rate is 50 µg/24 h for 7 days.
other ingredients are:Adhesive layer: styrene-isoprene copolymer, glycerin esters of hydrogenated rosin acids.
Outer protective layer: polyethylene terephthalate (PET).
Protective layer (to be removed): polyethylene terephthalate (PET) coated with silicone.

What Fem 7 looks like and contents of the pack

Fem 7 is a hexagonal, fully transparent transdermal system. Its inner (adhesive) layer is covered with a two-part, transparent protective foil.
4 transdermal systems and 12 transdermal systems
Not all pack sizes may be marketed.

Marketing authorization holder:

Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland

Manufacturer:

LTS Lohmann Therapie-Systeme AG
Lohmannstr.2
56626 Andernach
Germany
To obtain more detailed information, please contact the local representative of the marketing authorization holder at phone number: 22 307 71 66.

Date of last revision of the leaflet: