Femseven

PACKAGE LEAFLET: INFORMATION FOR THE USER

FemSeven 50, 50 micrograms/24 hours, transdermal patch

Estradiol
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. WHAT FEMSEVEN IS AND WHAT IT IS USED FOR

What is FemSeven?
FemSeven is a hormone replacement therapy (HRT) containing an oestrogen called estradiol hemihydrate, which
is a female sex hormone. FemSeven is used in women who have been in menopause for more than one year.
FemSeven is used for:
Relief of postmenopausal symptoms
During menopause, the amount of oestrogen produced by a woman's body decreases. This
can cause symptoms such as hot flushes affecting the face, neck, and chest. FemSeven alleviates these symptoms after
menopause. FemSeven will be prescribed to you only if your symptoms seriously interfere with your daily life.
Experience with treatment in women over 65 years of age is limited.
Prevention of osteoporosis
After menopause, some women may develop osteoporosis, meaning their bones may become more
fragile. Please consult your doctor regarding all available options.
If you are at increased risk of fractures due to osteoporosis and other medicinal treatments are not suitable for you,
you may use FemSeven to prevent postmenopausal osteoporosis.
FemSeven is suitable for women who have undergone hysterectomy (a surgical procedure to remove the uterus). If you have not had a hysterectomy, your doctor will normally prescribe another hormonal medicine (called a progestogen) to be taken in combination with this product. The progestogen helps protect the endometrium (the lining of the uterus). If you have had a hysterectomy due to endometriosis, your doctor may also prescribe a progestogen to protect any remaining endometrial tissue.

2. WHAT YOU SHOULD KNOW BEFORE USING FEMSEVEN

Medical history and regular check-ups
Taking HRT involves certain risks that must be considered when deciding whether to start or continue treatment.
Experience in treating women with premature menopause (due to early cessation of ovarian function or surgical removal of the ovaries) is limited. If you have premature menopause, the risks associated with taking HRT may differ. Consult your doctor.
Before you start (or restart) HRT, your doctor will ask you questions about your personal and family medical history. The doctor may decide to perform a medical examination, which may include a breast examination and/or a pelvic examination, if necessary.
Once you have started taking FemSeven, visit your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing treatment with FemSeven.
Have regular breast examinations as recommended by your doctor.

Do not use FemSeven
If any of the following conditions apply to you. If you have any doubts about any of the points listed, consult your doctor before taking FemSeven.

Do not use FemSeven:

• if you have, have had, or are suspected of having breast cancer;
• if you have an estrogen-sensitive cancer, such as cancer of the lining of the uterus (endometrium), or are suspected of having such a cancer;
• if you have experienced vaginal bleeding of unknown cause;
• if you have untreated excessive thickening of the lining of the uterus (endometrial hyperplasia);
• if you have or have had a blood clot in a vein (thrombosis), such as in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• if you have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency);
• if you have or have recently had an arterial disease caused by blood clots (such as heart attack, stroke or angina);
• if you have or have had liver disease and liver function tests have not returned to normal;
• if you have a hereditary condition (porphyria) characterized by the accumulation in the body of toxic substances (porphyrins);
• if you are allergic (hypersensitive) to estradiol hemihydrate or to any of the excipients of FemSeven (listed in section 6 “Contents of the pack and other information”). If you have any doubts about any of the points listed, consult your doctor before taking FemSeven. If any of the conditions listed above occur for the first time while taking FemSeven, stop taking it immediately and consult your doctor without delay.

Warnings and precautions
Talk to your doctor or pharmacist before using FemSeven.
FemSeven is not a contraceptive; therefore:

• for women who still have a uterus, a progestogen-containing treatment will be added for at least the last 12 days of each 28-day cycle;
• if less than 12 months have passed since your last menstrual period or if you are under 50 years of age, you may still need to use an additional contraceptive method to prevent pregnancy.

Consult your doctor.
Before starting treatment
Before starting treatment, inform your doctor if you have ever had any of the following conditions, as they may recur or worsen during treatment with FemSeven. In such cases, you may require more frequent medical check-ups:

• benign uterine tumors (fibroids within the uterus);
• growth of the uterine lining outside the uterus (endometriosis);
• previous abnormal thickening of the uterine lining (endometrial hyperplasia);
• an increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”);
• an increased risk of developing estrogen-dependent cancer (such as having a mother, sister or grandmother who had breast cancer);
• hypertension;
• liver disorder, such as benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• an autoimmune disease affecting multiple organs (systemic lupus erythematosus);
• epilepsy;
• asthma;
• a disease affecting the eardrum and hearing (otosclerosis);
• very high levels of fats in the blood (triglycerides);
• increased fluid retention due to heart or kidney problems.

If you are undergoing surgery
If you are scheduled for surgery, inform your surgeon that you are taking FemSeven. You may need to stop taking FemSeven approximately 4–6 weeks before surgery to reduce the risk of blood clots (see section 2 “Blood clots in a vein (thrombosis)”). Ask your doctor when you can resume using FemSeven.

Stop taking FemSeven and contact your doctor immediately
If you experience any of the following conditions while taking HRT:

• if you develop any condition listed under “Do not use FemSeven”;
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease;
• a marked increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• new-onset migraine-like headaches;
• if you become pregnant;
• if you notice signs of a blood clot such as:
  • painful swelling and redness in the legs;
  • sudden chest pain;
  • difficulty breathing. For further information, see “Blood clots in a vein (thrombosis)”.

HRT and cancer
Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Taking estrogen-only HRT increases the risk of developing excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer).
Taking a progestogen in addition to estrogen for at least 12 days of each 28-day cycle protects against this additional risk. Therefore, if you still have a uterus, your doctor will prescribe a separate progestogen-containing treatment. If you have had your uterus removed (hysterectomy), ask your doctor whether you can safely take this product without adding a progestogen.
In women who still have a uterus and who are not taking HRT, an average of 5 cases of endometrial cancer are diagnosed per 1,000 women aged between 50 and 65.
For women aged between 50 and 65 who still have a uterus and who take estrogen-only HRT, between 10 and 60 cases per 1,000 women are diagnosed (i.e. 5 to 55 additional cases), depending on the dose and duration of treatment.

Breast cancer:
Evidence suggests that taking combined estrogen-progestogen HRT, and possibly also estrogen-only HRT, increases the risk of breast cancer. This additional risk depends on the duration of HRT use. The increased risk becomes apparent after several years, but returns to normal within a few years (at most five) after stopping treatment.
For women who have had their uterus removed and who take estrogen-only HRT for 5 years, the increase in breast cancer risk has been shown to be slight or none.

Comparison
Considering women aged 50 to 79 not taking HRT, an average of 9–17 out of 1,000 will be diagnosed with breast cancer over a 5-year period. Among women aged 50 to 79 taking combined estrogen-progestogen HRT over 5 years, there will be 13 to 23 cases per 1,000 (i.e. 4 to 6 additional cases).

• Check your breasts regularly. Consult your doctor if you notice any changes such as:
  • skin retraction;
  • nipple changes;
  • lumps that you can see or feel.

In addition, you are advised to participate in mammographic screening programs when available. For mammographic screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are using hormone replacement therapy (HRT), as this therapy can increase breast density and thus affect the mammogram image. In cases of increased breast density, mammography may not detect all lumps.

Ovarian cancer:
Ovarian cancer is rare—much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestogen therapy has been associated with a slight increase in the risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, among women aged 50 to 54 not taking HRT, about 2 out of 2,000 will be diagnosed with ovarian cancer over 5 years. Among women taking HRT for 5 years, there will be about 3 cases per 2,000 women treated (i.e. about 1 additional case).

Effects of HRT on the heart and circulation
Blood clots in a vein (thrombosis)
The risk of blood clots in veins is approximately 1.3 to 3 times higher in women taking HRT than in those who do not, especially during the first year of treatment.
Blood clots can be serious; if a clot travels to the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The risk of developing a blood clot in a vein increases with age and in the presence of the following conditions. Signs of a blood clot are described in the section “Stop taking FemSeven and contact your doctor immediately”.
Inform your doctor if you are in any of the following situations:

• if you are unable to walk for long periods due to major surgery, injury, or illness (see also section 2 “If you are undergoing surgery”);
• if you are severely overweight (BMI >30 kg/m²);
• if you have a blood clotting disorder requiring long-term treatment with anticoagulant medication;
• if a close relative has had a blood clot in the legs, lungs, or another organ;
• if you have an autoimmune disease affecting multiple organs (systemic lupus erythematosus);
• if you have cancer.

Comparison
Considering women over 50 not taking HRT, on average, 4 to 7 out of 1,000 may develop a blood clot in a vein over a 5-year period.
Among women in their fifties taking combined estrogen-progestogen HRT for over 5 years, there will be 9 to 12 cases per 1,000 (i.e. 5 additional cases).
Among women in their fifties who have had a hysterectomy and have taken estrogen-only HRT for over 5 years, there will be 5 to 8 cases per 1,000 (i.e. 1 additional case).

Heart disease (heart attack)
There is no evidence that HRT can prevent heart attacks.
Women over 60 years of age who use combined estrogen-progestogen HRT have a slightly increased risk of developing heart disease compared to those not using HRT.
Women who have had a hysterectomy and who take estrogen-only HRT are not at increased risk of heart disease.

Stroke
The risk of stroke is about 1.5 times higher in women taking HRT than in those who do not. The number of additional stroke cases due to HRT use increases with advancing age.
Comparison
Considering women over 50 not taking HRT, on average, 8 out of 1,000 may have a stroke over a 5-year period. Among women in their fifties taking HRT, there will be 11 cases per 1,000 over 5 years (i.e. 3 additional cases).

Other conditions

• HRT does not prevent memory loss. Some evidence suggests an increased risk of memory loss in women who start HRT after age 65. Discuss this with your doctor.

Other medicines and FemSeven
Some medicines may interfere with the effect of FemSeven. This may cause irregular bleeding. These include:

• medicines for epilepsy (such as phenobarbital, phenytoin and carbamazepine);
• medicines for tuberculosis (such as rifampicin, rifabutin);
• medicines for HIV infections (such as nevirapine, efavirenz, ritonavir and nelfinavir);
• herbal preparations containing St. John’s wort (Hypericum perforatum).

Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including over-the-counter, herbal or natural products.

Laboratory tests
If you need to have a blood test, inform your doctor or laboratory staff that you are taking FemSeven, as this medicine may affect the results of certain tests.

Pregnancy and breastfeeding
FemSeven is intended for use only in postmenopausal women. If you become pregnant, stop taking FemSeven and contact your doctor.
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

3. HOW TO USE FEMSEVEN

Dosage regimen
FemSeven is an estrogen-only patch applied to the skin once weekly, i.e., the patch should be replaced with a new one every 7 days.
Use FemSeven exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Children: Use of FemSeven is not recommended in children.
Adults and elderly:

• Your doctor will aim to prescribe the lowest effective dose to treat your symptoms for the shortest possible time. Consult your doctor if you feel the dose is too strong or insufficient.
• You may normally start treatment on any day of your choice, unless you still have a uterus and are switching to FemSeven from a sequential HRT. In that case, you should start FemSeven immediately after the withdrawal bleed ends.
• Each patch is worn for 7 days and replaced with a new one the following day, so that you always have one patch on the skin. You should wear only one patch at a time.

Instructions for use

Application of the patch

1. Remove the patch from its pouch as shown in figures 1 and 2.
2. Peel off half of the protective liner starting from the S-shaped notch and apply the patch to the skin as shown in figures 3 and 4. Avoid touching the adhesive side of the

patch with your fingers, as this may impair proper adhesion.

3. Remove the other half of the protective liner, then press the patch onto the skin with the palm of your hand for at least 30 seconds, as shown in figures 5 and 6. Body heat will help the patch adhere better. Choose an area less prone to skin folds and friction from clothing, such as the buttocks, hip, or abdomen (avoid placing it under the waistband).

Do not apply the patch on or near the breasts.
Do not apply a new patch to the same skin area where the previous patch was removed.
Ensure the skin area where you apply the patch is clean, dry, and free of irritation or cracking.
If applied correctly, the patch is unlikely to detach during bathing, showering, or swimming.
Do not expose the patch to direct sunlight.
To remove the FemSeven patch, simply lift an edge and peel it off. Fold the patch in half (adhesive side to adhesive side) and dispose of it properly. If the patch starts to detach before the 7-day period is complete, remove it completely and apply a new one.
Replace it according to the regular schedule. If you forget to replace the patch when scheduled, do so as soon as possible and resume your regular schedule. If you still have a uterus, you are more likely to experience withdrawal bleeding if you forget to replace the patch on time.

If you use more FemSeven than you should
If you apply too many patches, overdose is unlikely and you should simply remove the extra patches.

If you forget to use FemSeven
Do not use a double dose to make up for a missed dose.
If you have any doubts about using this product, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE EFFECTS

Like all medicines, FemSeven can cause adverse effects, although not everyone experiences them.
For the list of adverse effects requiring treatment discontinuation, see section 2 "Stop taking FemSeven and contact your doctor immediately".
The following effects are reported more frequently in women taking HRT compared to those who do not use it:

• breast cancer;
• abnormal growth or cancer of the uterine lining (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible memory loss if HRT is started after age 65. For further information on these adverse effects, see section 2.

The following adverse effects may occur very commonly (in more than 1 in 10 people):

• Reactions at the application site:
• itching;
• redness (erythema);
• eczema;
• hives (urticaria);
• swelling (edema);
• skin pigmentation changes. These are generally mild skin reactions that usually disappear within 2 or 3 days after removing the patch.

The following adverse effects may occur commonly (may affect up to 1 in 10 people):

• headache;
• breast discomfort (e.g., mastalgia/mastopathy, breast enlargement).

The following adverse effects may occur uncommonly (may affect up to 1 in 100 people):

• hair changes, increased sweating;
• joint pain (arthralgia), leg cramps;
• dizziness, tingling in fingers or toes (paresthesia), migraine;
• anxiety, increased appetite, depression, difficulty sleeping (insomnia), nervousness;
• nausea, indigestion (dyspepsia), abdominal pain, vomiting;
• changes in blood pressure;
• chest pain;
• vein disorders;
• vaginal discharge, intermenstrual bleeding;
• swelling (edema), fatigue, changes in body weight.

The following potential adverse effects may occur rarely (may affect up to 1 in 1000 people):

• worsening of uterine fibroids (benign growths within the uterus).

The following adverse effects have been reported with other HRTs:

• gallbladder disease;
• various skin disorders:
• skin color changes, especially on the face or neck, known as "pregnancy mask" (chloasma);
• painful red nodules (erythema nodosum);
• rash with target-like redness or lesions (erythema multiforme).

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE FEMSEVEN

Keep out of the reach and sight of children.
Do not use FemSeven after the expiry date stated on the patch. The expiry date refers to the last day of the month.
Do not store FemSeven transdermal patches at temperatures above 30 °C.
Keep the patches in the foil pouches provided until the time of application of each patch.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. PACK CONTENTS AND OTHER INFORMATION

What FemSeven contains

• The active substance is: estradiol hemihydrate (1.5 milligrams).
• The other components are: transparent polyethylene terephthalate film, styrene-isoprene block copolymer, and glycerin esters of fully hydrogenated resins. The patches release 50 micrograms of estradiol over each 24-hour period.

Description of the appearance of FemSeven and pack contents
FemSeven transdermal patches are transparent, flexible, octagonal patches with rounded edges. Each
patch is coated with an adhesive and mounted on a larger, removable protective film.
The adhesive consists of a mixture of polymer and modified resin containing the active substances.
Each pack contains either 4 or 12 patches, allowing treatment for one or three months, respectively.

Marketing Authorization Holder
Theramex Ireland Limited
Kilmore House, Park Lane, Spencer Dock
Dublin 1, D01 YE64
Ireland

Manufacturer:
Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, Netherlands
LTS Lohmann Therapie-Systeme AG, Lohmannstr. 2, 56626 Andernach, Germany

This Patient Information Leaflet was last approved on:

PACKAGE LEAFLET: INFORMATION FOR THE USER
FemSeven® 75, 75 micrograms/24 hours, transdermal patch
Estradiol

Read this entire leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. WHAT FEMSEVEN IS AND WHAT IT IS USED FOR

What is FemSeven?
FemSeven is a hormone replacement therapy (HRT) containing an oestrogen called estradiol hemihydrate, which
is a female sex hormone. FemSeven is used by women who have been in menopause for more than one year.
FemSeven is used for:
Relief of postmenopausal symptoms
During menopause, the amount of oestrogen produced by a woman's body decreases. This
can cause symptoms such as hot flushes affecting the face, neck, and chest. FemSeven relieves these symptoms after
menopause. FemSeven will be prescribed to you only if your symptoms seriously interfere with your daily life.
Experience with treatment in women over 65 years of age is limited.
Prevention of osteoporosis
After menopause, some women may develop osteoporosis, meaning their bones can become more
fragile. Please consult your doctor regarding all available options.
If you are at increased risk of fractures due to osteoporosis and other medications are not suitable for you,
you may use FemSeven to prevent osteoporosis after menopause.
FemSeven is suitable for women who have undergone a hysterectomy (a surgical procedure to remove the uterus). If you have not had a hysterectomy, your doctor will normally prescribe another hormonal treatment (called a progestogen) to be taken together with this medicine. The progestogen helps protect the endometrium (the lining of the uterus). If you have had a hysterectomy due to endometriosis, your doctor may also prescribe a progestogen to protect any remaining endometrial tissue.

2. WHAT YOU SHOULD KNOW BEFORE USING FEMSEVEN

Medical history and regular check-ups
Taking hormone replacement therapy (HRT) involves certain risks that should be considered when deciding whether to start or continue treatment.
Experience in treating women with premature menopause (due to early cessation of ovarian function or surgical removal of the ovaries) is limited. If you have premature menopause, the risks associated with HRT may differ. Please consult your doctor.
Before you start (or restart) HRT, your doctor will ask you questions about your personal and family medical history. Your doctor may decide to perform a medical examination, which may include a breast examination and/or an internal pelvic examination, if necessary.
Once you have started taking FemSeven, attend regular check-ups with your doctor (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing treatment with FemSeven.
Have regular breast examinations as recommended by your doctor.

Do not use FemSeven
If any of the following conditions apply to you. If you have any doubts about any of the points listed, consult your doctor before taking FemSeven.
Do not use FemSeven:

• if you have, have had, or are suspected of having breast cancer;
• if you have an estrogen-sensitive cancer, such as cancer of the lining of the uterus (endometrium), or are suspected of having one;
• if you have experienced vaginal bleeding of unknown cause;
• if you have untreated excessive thickening of the lining of the uterus (endometrial hyperplasia);
• if you have or have had a blood clot in a vein (thrombosis), such as in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• if you have a blood clotting disorder (such as protein C deficiency, protein S deficiency, or antithrombin deficiency);
• if you have or have recently had an arterial disease caused by blood clots (such as heart attack, stroke, or angina);
• if you have or have had liver disease and liver function tests have not returned to normal;
• if you have a hereditary disease (porphyria) characterized by the accumulation of toxic substances (porphyrins) in the body;
• if you are allergic (hypersensitive) to estradiol hemihydrate or any of the excipients of FemSeven (listed in section 6 “Contents of the pack and other information”). If you have any doubts about any of the points listed, consult your doctor before taking FemSeven. If any of the conditions listed above occur for the first time while you are taking FemSeven, stop taking it immediately and consult your doctor without delay.

Warnings and precautions
Talk to your doctor or pharmacist before using FemSeven.
FemSeven is not a contraceptive; therefore:

• for women who still have a uterus, a progestogen-containing treatment will be added for at least the last 12 days of each 28-day cycle;
• if less than 12 months have passed since your last menstrual period, or if you are under 50 years of age, you may still need to use an additional contraceptive method to prevent pregnancy. Consult your doctor.

Before starting treatment
Before starting treatment, inform your doctor if you have ever had any of the following conditions, as they may recur or worsen during treatment with FemSeven. In such cases, you may need to see your doctor more frequently for check-ups:

• benign uterine tumors (fibroids within the uterus);
• growth of the uterine lining outside the uterus (endometriosis);
• previous abnormal growth of the uterine lining (endometrial hyperplasia);
• increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”);
• increased risk of developing estrogen-dependent cancer (e.g., if you have a mother, sister, or grandmother who had breast cancer);
• high blood pressure;
• liver disorder, such as benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• an autoimmune disease affecting multiple organs (systemic lupus erythematosus);
• epilepsy;
• asthma;
• a disease affecting the eardrum and hearing (otosclerosis);
• very high levels of fat in the blood (triglycerides);
• increased fluid retention due to heart or kidney problems.

If you are undergoing surgery
If you are scheduled for surgery, inform your surgeon that you are taking FemSeven. You may need to stop taking FemSeven approximately 4–6 weeks before surgery to reduce the risk of blood clots (see section 2 “Blood clots in a vein (thrombosis)”). Ask your doctor when you can resume using FemSeven.

Stop taking FemSeven and contact your doctor immediately
If you experience any of the following conditions while taking HRT:

• if you develop any condition listed under “Do not use FemSeven”;
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease;
• a marked increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• new-onset migraine-like headaches;
• if you become pregnant;
• if you notice signs of a blood clot such as:
  • painful swelling and redness in the legs;
  • sudden chest pain;
  • difficulty breathing. For further information, see “Blood clots in a vein (thrombosis)”.

HRT and cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Taking estrogen-only HRT increases the risk of developing excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer).
Taking a progestogen in addition to estrogen for at least 12 days of each 28-day cycle protects against this additional risk. Therefore, if you still have a uterus, your doctor will prescribe a separate progestogen-containing treatment. If you have had your uterus removed (hysterectomy), ask your doctor whether you can safely take this product without adding a progestogen-containing treatment.
Among women who still have a uterus and are not taking HRT, an average of 5 cases of endometrial cancer are diagnosed per 1,000 women aged 50 to 65 years.
Among women aged 50 to 65 years who still have a uterus and take estrogen-only HRT, between 10 and 60 cases per 1,000 women are diagnosed (i.e., 5 to 55 additional cases), depending on the dose and duration of treatment.
FemSeven contains a higher dose of estrogen than other estrogen-only HRT products. The risk of endometrial cancer associated with using FemSeven together with a progestogen-containing treatment is unknown.

Breast cancer:
Evidence suggests that taking combined estrogen-progestogen HRT, and possibly also estrogen-only HRT, increases the risk of breast cancer. This additional risk depends on the duration of HRT use. The increased risk becomes apparent after several years but returns to normal within a few years (at most five) after stopping treatment.
In women who have had their uterus removed and who take estrogen-only HRT for 5 years, the increased risk of breast cancer is minimal or none.

Comparison
Among women aged 50 to 79 years not taking HRT, an average of 9 to 17 out of 1,000 will be diagnosed with breast cancer over a 5-year period. Among women aged 50 to 79 years taking combined estrogen-progestogen HRT over 5 years, 13 to 23 cases per 1,000 will occur (i.e., 4 to 6 additional cases).

• Check your breasts regularly. Consult your doctor if you notice any changes such as:
  • skin retraction;
  • nipple changes;
  • lumps you can see or feel.

Additionally, we recommend that you participate in mammographic screening programs when available. For mammographic screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are using hormone replacement therapy (HRT), as this therapy can increase breast density and thus affect the mammogram image. With increased breast density, mammography may not detect all lumps.

Ovarian cancer:
Ovarian cancer is rare—much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestogen therapy has been associated with a slight increase in the risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, among women aged 50 to 54 years not taking HRT, about 2 out of 2,000 will be diagnosed with ovarian cancer over 5 years. Among women taking HRT for 5 years, there will be about 3 cases per 2,000 women treated (i.e., about 1 additional case).

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)
The risk of venous blood clots is approximately 1.3 to 3 times higher in women taking HRT than in those who do not, especially during the first year of use.
Venous blood clots can be serious; if a clot travels to the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The risk of developing a venous blood clot increases with age and in the presence of the following conditions. Signs of a blood clot are described in the section “Stop taking FemSeven and contact your doctor immediately”.
Inform your doctor if you are in any of the following situations:

• if you are unable to walk for long periods due to major surgery, injury, or illness (see also section 2 “If you are undergoing surgery”);
• if you are severely overweight (BMI >30 kg/m²);
• if you have a blood clotting disorder requiring long-term treatment with anticoagulant medication;
• if a close relative has had a blood clot in the legs, lungs, or another organ;
• if you have an autoimmune disease affecting multiple organs (systemic lupus erythematosus);
• if you have cancer.

Comparison
Among women over 50 years of age not taking HRT, an average of 4 to 7 out of 1,000 may develop a venous blood clot over a 5-year period.
Among women aged 50 who take combined estrogen-progestogen HRT for more than 5 years, 9 to 12 cases per 1,000 will occur (i.e., 5 additional cases).
Among women aged 50 who have had a hysterectomy and have taken estrogen-only HRT for more than 5 years, 5 to 8 cases per 1,000 will occur (i.e., 1 additional case).

Heart disease (heart attack)
There is no evidence that HRT can prevent heart attacks.
Women over 60 years of age who use combined estrogen-progestogen HRT have a slightly increased risk of developing heart disease compared to those not using HRT.
Women who have had a hysterectomy and take estrogen-only HRT are not at increased risk of heart disease.

Stroke
The risk of stroke is about 1.5 times higher in women taking HRT than in those who do not. The number of additional stroke cases due to HRT use increases with advancing age.

Comparison
Among women over 50 years of age not taking HRT, an average of 8 out of 1,000 may have a stroke over a 5-year period. Among women aged 50 who take HRT, 11 cases per 1,000 will occur over 5 years (i.e., 3 additional cases).

Other conditions

• HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start HRT after age 65. Please consult your doctor.

Other medicines and FemSeven
Some medicines may interfere with the effect of FemSeven, which may cause irregular bleeding. These include:

• medicines for epilepsy (such as phenobarbital, phenytoin, and carbamazepine);
• medicines for tuberculosis (such as rifampicin, rifabutin);
• medicines for HIV infections (such as nevirapine, efavirenz, ritonavir, and nelfinavir);
• herbal preparations containing St. John’s wort (Hypericum perforatum).

Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including over-the-counter, herbal, or other natural products.

Laboratory tests
If you are scheduled for a blood test, inform your doctor or laboratory staff that you are taking FemSeven, as this medicine may affect the results of certain tests.

Pregnancy and breastfeeding
FemSeven is intended for use only in postmenopausal women. If you become pregnant, stop taking FemSeven and contact your doctor.
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

3. HOW TO USE FEMSEVEN

Dosage regimen
FemSeven is an estrogen-only transdermal patch applied to the skin once weekly, continuously—i.e., the patch should be replaced every 7 days. Always use FemSeven exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Children: The use of FemSeven is not recommended in children.
Adults and elderly:

• Your doctor will generally prescribe the lowest effective dose to treat your symptoms for the shortest possible duration. Consult your doctor if you feel the dose is too strong or insufficient.
• You may normally start treatment on any day you choose, unless you still have a uterus and are switching to FemSeven from a sequential HRT regimen. In that case, start FemSeven immediately after the withdrawal bleed ends.
• Each patch is worn for 7 days and replaced with a new one the following day, ensuring you always have a patch on the skin. You should wear only one patch at a time.

Method of administration

Applying the patch

1. Remove the patch from its sachet as shown in figures 1 and 2.
2. Peel off half of the protective liner starting from the S-shaped notch and apply the patch to the skin as shown in figures 3 and 4. Avoid touching the adhesive side with your fingers, as this may reduce its adhesion.
3. Remove the other half of the protective liner, then press the patch firmly onto the skin with the palm of your hand for at least 30 seconds, as shown in figures 5 and 6. Body heat will help the patch adhere better. Choose an area less prone to skin folds and friction from clothing, such as the buttocks, hips, or abdomen (avoid placing it under the waistband).

Do not apply the patch on or near the breasts.
Do not apply a new patch to the same skin area where the previous patch was placed.
Ensure the skin area where you apply the patch is clean, dry, and free of irritation or cracking.
If applied correctly, the patch is unlikely to detach during bathing, showering, or swimming.
Do not expose the patch to direct sunlight.
To remove the FemSeven patch, simply lift the edge and peel it off. Fold the patch in half (adhesive side to adhesive side) and dispose of it safely. If the patch starts to detach before the 7-day period is complete, remove it completely and apply a new one. Replace it according to the regular schedule.
If you forget to replace the patch on time, do so as soon as possible and resume your regular schedule. If you still have a uterus, you are more likely to experience withdrawal bleeding if you miss a patch replacement on time.

If you use more FemSeven than you should
If you apply too many patches, overdose is unlikely; simply remove the extra patches.

If you forget to use FemSeven
Do not use a double dose to make up for a missed dose.
If you have any questions about using this product, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, FemSeven can cause adverse reactions,
although not everyone experiences them.
For a list of adverse reactions requiring treatment discontinuation, see section 2 “Stop taking FemSeven
and contact your doctor immediately”.
The following effects are reported more frequently in women taking HRT compared to those who do not use it:

• breast cancer;
• abnormal growth or cancer of the uterine lining (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. For further information on these adverse reactions, see section 2.

The following adverse reactions may occur very commonly (in more than 1 in 10 people):

• Reactions at the application site:
• itching;
• redness (erythema);
• eczema;
• urticaria;
• swelling (edema);
• skin pigmentation changes. These are generally mild skin reactions that usually disappear within 2 or 3 days after removing the patch.

The following adverse reactions may occur commonly (may affect up to 1 in 10 people):

• headache;
• breast discomfort (e.g., mastalgia/breast disorders, breast enlargement).

The following adverse reactions may occur uncommonly (may affect up to 1 in 100 people):

• hair changes, increased sweating;
• joint pain (arthralgia), leg cramps;
• dizziness, tingling in fingers or toes (paresthesia), migraine;
• anxiety, increased appetite, depression, difficulty sleeping (insomnia), nervousness;
• nausea, indigestion (dyspepsia), abdominal pain, vomiting;
• changes in blood pressure;
• chest pain;
• vein disorders;
• vaginal discharge, intermenstrual bleeding;
• swelling (edema), fatigue, changes in body weight.

The following potential adverse reactions may occur rarely (may affect up to 1 in 1000 people):

• worsening of uterine fibroids (benign growths within the uterus).

The following adverse reactions have been reported with other HRTs:

• gallbladder diseases;
• various skin disorders:
• skin color changes, especially on the face or neck, known as “pregnancy mask” (chloasma);
• painful red nodules (erythema nodosum);
• rash with target-like redness or lesions (erythema multiforme).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist.
You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse . By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE FEMSEVEN

Keep out of the reach and sight of children.
Do not use FemSeven after the expiry date stated on the patch. The expiry date refers to the last day of the month.
Do not store FemSeven transdermal patches at temperatures above 30 °C.
Keep the patches in the sachets in which they are contained until the time of application of each patch.
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. PACK CONTENTS AND OTHER INFORMATION

What FemSeven contains

• The active substance is: estradiol hemihydrate (2.25 milligrams).
• The other components are: transparent sheet of polyethylene terephthalate, styrene-isoprene block copolymer, and diglycerin esters of completely hydrogenated resins. The patches release 75 micrograms of estradiol over each 24-hour period.

Description of the appearance of FemSeven and pack contents
FemSeven transdermal patches are transparent, flexible, octagonal patches with rounded edges. Each
patch is coated with an adhesive and affixed to a larger, removable protective film.
The adhesive consists of a mixture of polymer and modified resin containing the active substances.
Each pack contains either 4 or 12 patches, allowing treatment for one or three months respectively.
Marketing Authorisation Holder:
Theramex Ireland Limited
Kilmore House, Park Lane, Spencer Dock
Dublin 1, D01 YE64
Ireland
Manufacturer:
Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, Netherlands
LTS Lohmann Therapie-Systeme AG, Lohmannstr.2, 56626 Andernach, Germany
This leaflet was last approved on: