ESTREVA <0.1%> Gel

Зміст інструкції

1. ESTREVA 0,1% gel
   1. WHAT IS ESTREVA 0.1% gel AND WHAT IS IT USED FOR
   2. PRIMA DI USARE ESTREVA 0,1% gel
   3. HOW TO USE ESTREVA 0.1% gel
   4. POSSIBLE SIDE EFFECTS
   5. HOW TO STORE ESTREVA 0.1% gel
   6. FURTHER INFORMATION

ESTREVA 0,1% gel

Estradiol

Read this leaflet carefully before using this medicine.

• 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. Never give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If any of the side effects gets worse, or if you notice any side effect not listed in this leaflet, tell your doctor or pharmacist.

Contents of this leaflet:

• 1. What Estreva 0,1% gel is and what it is used for
• 2. Before you use Estreva 0,1% gel
• 3. How to use Estreva 0,1% gel
• 4. Possible side effects
• 5. How to store Estreva 0,1% gel
• 6. Further information

1. WHAT IS ESTREVA 0.1% gel AND WHAT IS IT USED FOR

Estreva 0.1% gel contains estrogen, a natural sex hormone present in the human body and
belonging to the group of drugs for Hormone Replacement Therapy (HRT). It compensates for the
loss of estrogen leading to a reduction of disorders.
Estreva 0.1% gel is indicated for the treatment of menopausal symptoms (such as hot flashes) caused by
estrogen deficiency in postmenopausal women.
Experience with the treatment of women over 65 years of age is limited.

2. PRIMA DI USARE ESTREVA 0,1% gel

Medical checks
Your doctor will advise you whether or not you should use hormone replacement therapy (HRT). The use of
HRT involves some risks that need to be considered when deciding whether to start or
continue taking it.
Before you start using Estreva 0,1% gel, your doctor will ask you about your personal and family medical history. Your doctor should perform a breast and abdominal examination and may perform a
gynaecological examination.
Your doctor should tell you what changes in the breasts you should report to them and may ask you to have a
mammogram.
Once you have started therapy with Estreva 0,1% gel, regular medical check-ups (at least annually) should still be carried out. During these check-ups, the risks and benefits should be reassessed
to determine whether the treatment should be continued.

Do not use Estreva 0,1% gel

• if you are allergic (hypersensitive) to the active ingredient (estradiol) or to any of the excipients of Estreva 0,1% gel (listed in section 6 Further information);
• if you have or have ever had a blood clot in a leg vein (deep vein thrombosis) or in the

lungs (pulmonary embolism);

• if you have a blood coagulation disorder (e.g. Protein C, Protein S or antithrombin deficiency);
• if you have or have had a blood clot in an artery of the heart (angina pectoris, myocardial infarction) or of the brain (stroke) or of another organ;
• if you have or have ever had or your doctor believes that you may have breast cancer;
• if you have a cancer sensitive to oestrogens, such as cancer of the uterine lining (endometrium) or your doctor believes that you may have it;
• if the uterine lining shows excessive growth (endometrial hyperplasia);
• if you suffer from genital bleeding whose cause has not yet been determined;
• if you have or have had liver disease. You should not use Estreva 0,1% gel until your liver function has returned to normal;
• if you have a rare blood disease called "porphyria" which is inherited.

Take particular care with Estreva 0,1% gel
Estreva 0,1% gel contains propylene glycol which can cause skin irritation.

Tell your doctor, before you start using Estreva 0,1% gel, if you have or have previously had
any of the following conditions and/or if these have worsened during pregnancy or previous
hormone therapy. These may recur or worsen during treatment with Estreva
0,1% gel. If this is the case, your doctor may require more frequent check-ups:

• if you have high blood pressure (arterial hypertension);
• if you are at increased risk of developing blood clots in the veins or lungs;
• if you have high blood sugar levels (diabetes) with or without vascular disorders;
• if you have a condition characterized by the presence of uterine lining outside the uterus that causes pain and bleeding (endometriosis);
• if you have a benign tumor of the uterus (uterine fibroids);
• if the uterine lining shows excessive growth (endometrial hyperplasia);
• if you have an increased risk of developing a cancer sensitive to oestrogens, for example if a family member (mother, sister or daughter) has already had breast cancer;
• if you have liver diseases such as a benign tumor (hepatic adenoma);
• if you have gallstones;
• if you suffer from epilepsy (see also section Use with other medicines);
• if you have severe headaches or migraines;
• if you have heart or kidney dysfunction;
• if you suffer from asthma;
• if you have a serious skin condition (systemic lupus erythematosus);
• if you have a disease that causes hearing loss (otosclerosis).

If you are already taking Estreva 0,1% gel and the conditions in question worsen, you should inform
your doctor about this.
Stop taking Estreva 0,1% gel immediately
If you have had any of the conditions mentioned in the "Do not use Estreva 0,1% gel" section, or if one of the following situations occurs:

• if you develop yellowing of the skinor the whites of the eyes (jaundice) or if your liver functionworsens;
• if your blood pressuresuddenly becomes much higher (symptoms may include headache, fatigue and dizziness);
• if you have a headache similar to migrainefor the first time;
• if you become pregnant.

You should also inform your doctor:

• if you are going to have surgery;
• if you need to remain immobilised for a long period;
• if you have contracted another illness.

What risks are associated with the use of Estreva 0,1% gel?
HRT AND EFFECTS ON THE HEART OR CIRCULATORY SYSTEM
Blood clots (thrombosis)
Immediately inform your doctor if you experience swelling accompanied by pain in a
leg, sudden chest pain or difficulty breathing while usingEstreva0,1% gel.
These may be symptoms of venous thrombosis or pulmonary embolism, in which case you
should immediately stop taking Estreva 0,1% gel.
Blood clots are not always dangerous, but there is a possibility that a clot will reach the lungs, where
it can cause chest pain, shortness of breath, collapse or even death.
The risk of venous thrombosisis 1.3 to 3 times higher in women taking HRT compared to
those who are not, especially during the first year of treatment.
Comparison
Observing 50-year-old women who are not taking HRT, on average, over a period of 5
years, it is expected that 4 to 7 of them per 1000 will develop a blood clot.
For 50-year-olds taking HRT over 5 years, 5 more cases of thrombosis will occur
per 1000 patients.
For 50-year-olds who have had their uterus removed and who have taken HRT based on oestrogens alone
for more than 5 years, 1 more case of thrombosis will occur per 1000 patients.
The risk of venous thrombosis is higher:

• if you are taking medicines that contain oestrogens (such as HRT);
• if you are of advanced age;
• if you have cancer;
• during pregnancy and the postpartum period;
• if a close family member has already had venous thrombosis;
• if you are severely overweight;
• if you suffer from systemic lupus erythematosus (a disease of the immune system);
• if you are immobilised for a long time(e.g. in bed), if you have a traumaor have undergone major surgery. In these conditions, it may be necessary to temporarily interrupttherapy with Estreva 0,1% gel. You may need to stop it at least 4-6 weeks before scheduled surgery. It is not clear whether the presence of varicose veins increases the risk of venous thrombosis.

Inform your doctorifany of these conditions apply to you.If you are using an anticoagulant, the risks and benefits of using HRT must be carefully assessed.

Coronary artery disorders
Stop taking the medicine andcontact your doctor immediately if you experience chest pain
that radiates to your arm or neck.This pain may be a symptom of heart disease.
There is no evidence that HRT helps prevent heart disease. Women over 60
years of age who take combined oestrogen/progestin HRT have a slightly higher
probability of developing heart disease compared to women who do not take any HRT. Because the risk
of developing coronary heart disease depends significantly on age, the number of additional cases of
coronary heart disease due to the use of the oestrogen and progestin combination is very low in healthy women near menopause, but increases with advancing age. Data from randomized controlled studies have not shown an increased risk of coronary heart disease in women who have undergone hysterectomy and
are taking oestrogen-only therapy.

Stroke risk
Stop taking the medicine and contact your doctor immediately if you experience
unexplained migraine-like headache, withorwithout visual disturbances. This headache may
be an early symptom of stroke.
The risk of stroke is approximately 1.5 times higher in women taking HRT compared to
those who are not. The risk of women taking HRT compared to those who are not
taking it does not change based on age or time since the start of menopause. However, because
the risk of stroke depends strongly on age, the overall risk of stroke in women taking
HRT will increase with age.
Comparison
Observing 50-year-old women who are not taking HRT, on average, over a period of 5 years, it is
expected that 8 of them per 1000 will be affected by a stroke.
For 50-year-olds taking HRT over 5 years, 3 more cases of stroke will occur per 1000
patients.

HRT AND THE RISK OF DEVELOPING CANCER
Excessive growth of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining
(endometrium):
Taking oestrogen for a long period of time increases the risk of excessive growth of the uterine lining (endometrial hyperplasia) and endometrial cancer in women
with an intact uterus. Taking a progestin in addition to oestrogen for at least 12 days of
every 28-day cycle protects against this additional risk. For this reason, your doctor may
prescribe you a progestin separately if you still have an intact uterus. If you have undergone
surgical removal of the uterus (hysterectomy), your doctor will explain whether you can safely take
this medicine without a progestin.
Irregular bleeding may occur during the first few months of treatment. Contact your doctor if:

• this bleeding continues to occur after the first few months of treatment;
• it occurs after you have been using Estreva 0,1% gel for a while;
• it persists after stopping treatment with Estreva 0,1% gel. The doctor will investigate the cause, which may include performing a biopsy of the uterine lining to find out if you have endometrial cancer.

Comparison
Observing women who still have a uterus and are not taking HRT, on average, 5 out of 1000 will
be diagnosed with endometrial cancer between the ages of 50 and 65.
For women taking oestrogen-only HRT, 5 to 55 more cases of endometrial cancer will occur
per 1000 patients between the ages of 50 and 65, depending on the dose and duration
of therapy.
Taking a progestin in addition to oestrogen for at least 12 days of every 28-day
cycle protects against this additional risk.

Breast cancer
Evidence suggests that taking combined oestrogen/progestin and, potentially,
also oestrogen-only HRT increases the risk of breast cancer. This depends on the
duration of HRT and the additional risk is visible after about 3 years. However, this risk returns to
normal levels within a few years (at most five) after stopping treatment.
For women who have had their uterus removed and who take oestrogen-only HRT for 5 years, a mild or non-existent increase in the risk of breast cancer has been demonstrated.
Contact your doctor if you notice changes in the breasts such as orange peel appearance,
changes in the nipple skin, or lumps that can be seen or felt.
Your doctor may advise you to have a medical check-up including a mammogram.
Comparison
According to one study, among women aged between 50 and 65 who do not take HRT, on average,
9-12 out of 1000 will be diagnosed with breast cancer over a period of 5 years. Among women
aged between 50 and 65 who take combined oestrogen-progestin HRT over 5 years, 6 more cases of breast cancer will occur per 1000 patients.
According to another study, among women aged between 50 and 79 who do not take HRT, in
average, 17 out of 1000 will be diagnosed with breast cancer over a period of 5 years.
Among women aged between 50 and 79 who take combined oestrogen-progestin HRT
over 5 years, 4 more cases of breast cancer will occur per 1000 patients.
In addition, we recommend that you participate in mammography screening programs when you have
the opportunity. For mammography screening, it is important to inform the nurse/healthcare
professional performing the X-ray that you are using hormone replacement therapy (HRT),
because this therapy can increase breast density and therefore affect the image
obtained with mammography. In case of increased breast density, mammography may not
be able to detect all nodules.

Ovarian cancer:
Ovarian cancer is rare - much rarer than breast cancer. The use of a therapy based on
estrogens alone or estrogen-progestins has been associated with a slight increase in the risk of ovarian
cancer.
The risk of ovarian cancer varies depending on age. For example, in women aged between 50 and
54 who are not undergoing HRT, about 2 out of 2,000 will receive a diagnosis of ovarian
cancer over a 5-year period. For women who are undergoing HRT for 5 years, there will be about 3
cases per 2,000 women treated (i.e., about 1 more case).

HRT AND OTHER DISORDERS

• If you suffer from heart or kidney dysfunctionyou should be monitored during the period of taking Estreva 0,1% gel.
• If you have very high levels of triglycerides in the blood(hypertriglyceridemia) you should be monitored during the period of taking Estreva 0,1% gel. HRT does not prevent memory loss. The risk of memory loss may be slightly higher in women who start taking HRT after the age of 65. Consult your doctor for information on this topic.

Consult your doctor if you have any of the above conditions or have had them in the past.
Possible transfer of estradiol
In case of close skin contact, estradiol may be transferred to another person if
the treated area is not covered.
For this reason, it is recommended to observe the following precautions:

• wash your hands with soap and water after applying the gel,
• cover the application area with clothing once the gel has dried,
• shower before intimate contact.

If you think that estradiol has been transferred to another person (an adult or a child), wash
the affected skin area with soap and water.
Taking Estreva 0,1% gel with other medicines
Some medicines reduce the effectiveness of Estreva 0,1% gel, especially if you are taking:

• medicines for the treatment of epilepsy (e.g. carbamazepine, phenobarbital, phenytoin, primidone);
• medicines for the treatment of tuberculosis (rifampicin), another infectious disease (e.g. rifabutin);
• medicines for AIDS (ritonavir, nelfinavir, nevirapine, efavirenz);
• herbal preparations containing St. John's wort (Hypericum perforatum).

Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those without a prescription.

Pregnancy and breastfeeding
Pregnancy: do not use Estreva 0,1% gel during pregnancy.
If you become pregnant while using Estreva 0,1% gel, stop treatment immediately.

Breastfeeding:do not use Estreva 0,1% gel if you are breastfeeding.
Ask your doctor or pharmacist for advice before taking any medicine

Driving and using machines
No particular effects are expected.

Important information about some excipients of Estreva 0,1% gel
Estreva 0,1% gel contains propylene glycol (see also paragraph “Take special care with Estreva 0,1% gel”)

3. HOW TO USE ESTREVA 0.1% gel

Dosage

Always use Estreva 0.1% gel exactly as your doctor has instructed. If you have any doubts, consult your

doctor or pharmacist.
The individual dose may vary from 0.5 to 3 g of gel per day.
The usual dose is 1.5 g of gel per day (3 presses of the measuring pump) for a period of 24 to
28 days per month followed by 2 to 7 days without treatment. Each press releases a dose of
0.5 g of gel.
During the period of treatment interruption, bleeding similar to
menstruation may occur. This bleeding is normal and of limited nature.
Your doctor will prescribe Estreva 0.1% gel according to your needs. He/she may modify the dose and
duration based on your response to treatment. Your doctor will prescribe the minimum dose for
treating symptoms for the shortest possible period. Consult your doctor if you feel that the
dosage is too high or too low.
Your doctor may also prescribe Estreva 0.1% gel to be taken continuously without interruption.
For women with an intact uterus, the addition of a progestin hormone for at least 12 days per cycle is
mandatory to prevent the risk of excessive growth of the uterine lining (estrogen-induced endometrial hyperplasia).
If you feel that the effect of Estreva 0.1% gel is too strong or too weak, inform your doctor.
Route of administration
This medicine must be applied to the skin.
How to apply Estreva 0.1% gel

• Remove the cap.
• Hold the bottle with one hand and, with the other hand under the applicator to take the gel, press the dosing pump to obtain the required dose. You may need to press the pump several times on first use, this is to activate the device. The first dose may not be accurate and it is recommended to discard it.
• Between each press, allow the applicator to return to its initial position.
• The gel should be applied to clean, dry and intact skin (on the abdomen, thighs, arms, shoulders). The gel should be applied to an area equivalent to twice the size of a hand.
• The gel should not be applied to the breasts or mucous membranes (inside the mouth, nose, ears or genitals).
• Contact with eyes should be avoided.
• There is no need to massage but it is recommended to allow the gel to dry for 2 minutes before getting dressed. The gel is not greasy.
• It is recommended to wash your hands after applying the gel.

Frequency of use
The gel should preferably be applied in the morning or evening, once a day after washing.
Duration of treatment
Follow your doctor's prescription. He/she will decide the duration of treatment. He/she may however
need to modify it.
If you wish to stop treatment before the time, you must discuss this with your doctor.
On average, a 50 g bottle is sufficient for 1 month of treatment.

If you use more Estreva 0.1% gel than you should
An overdose may cause nausea, vomiting and vaginal bleeding. No specific
treatment is necessary. If symptoms persist, inform your doctor.

If you forget to use Estreva 0.1% gel
Do not use a double dose to compensate for forgetting the dose.
If you have forgotten to apply the gel on the scheduled day, apply it as soon as possible and resume the
treatment with the prescribed dose.
If you have not applied the gel for several days, irregular bleeding may occur.
If in doubt, consult your doctor.

If you stop treatment with Estreva 0.1% gel
Upon discontinuation of treatment, menopausal symptoms related to estrogen deficiency may reappear. If you have any doubts about the use of Estreva 0.1% gel, consult your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Estreva 0.1% gel can cause side effects, although not everybody gets them.

Common(may affect up to 1 in 10 people):

• irregular and abnormal vaginal or uterine bleeding (dysmenorrhea, breakthrough bleeding or spotting)
• headache
• abdominal pain
• nausea
• skin rash
• itching
• change in weight (increase or decrease)

Uncommon(may affect up to 1 in 1,000 people):

• allergy (hypersensitivity reactions),
• depressed mood and mood disorders,
• dizziness,
• vision disorders,
• palpitations,
• stomach pain (dyspnea),
• skin inflammation causing red, painful nodules (erythema nodosum),
• skin pigmentation disorders (chloasma/melasma),
• urticaria (hives),
• swelling (edema),
• breast pain
• breast tension

Rare(may affect up to 1 in 10,000 people):

• excess hair growth on the face and body (hirsutism)
• breast enlargement
• swelling
• intolerance to contact lenses
• migraine
• anxiety
• changes in libido (increase or decrease)
• vomiting
• acne
• muscle cramps
• fatigue
• pre-menstrual syndrome (e.g. fatigue, abdominal pain, headache, breast tenderness, irritability)
• vaginal discharge (leucorrhea)

Other known side effects that may occur with hormone replacement therapy are:

• benign and malignant tumors influenced by estrogen hormones; for example, endometrial cancer, breast cancer (see paragraph 2),
• heart attack (myocardial infarction) and stroke,
• gallbladder disorders,
• disorders of the skin or subcutaneous tissue such as:
• chloasma (yellow-brown pigmented patches, also referred to as pregnancy spots)
• erythema multiforme (type of rash with papules, blisters, or fluid accumulation)
• erythema nodosum (type of rash with painful bluish-red nodules)
• vascular purpura (pinpoint bleeding skin spots)
• venous thrombosis and pulmonary embolism occur more frequently than in women who are not taking hormone replacement therapy,
• possible dementia.

If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet,
Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the
national reporting system at: www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects you can help provide more information on the safety
of this medicine.

5. HOW TO STORE ESTREVA 0.1% gel

Keep Estreva 0.1% gel out of the reach and sight of children.
Do not use Estreva 0.1 % gel after the expiry date which is stated on the label and the bottle.
The expiry date refers to the last day of the month.
No special storage conditions are required.
Do not use Estreva 0.1% gel if you notice visible signs of deterioration of the medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. FURTHER INFORMATION

What Estreva 0.1% gel contains
The active ingredient is: Estradiol (1 mg per 1 g of gel).
The excipients are: 96% Ethanol, purified water, propylene glycol, diethylene glycol monoethyl ether (TRANSCUTOL), carbomer (CARBOPOL 1382), trolamine, disodium edetate.

Description of the appearance of Estreva 0.1% gel and contents of the pack
This medicine is a translucent and odorless gel.
Packs of one or three tubes of 50 g.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
THERAMEX IRELAND LIMITED,
3RD FLOOR, KILMORE HOUSE, PARK LANE, SPENCER DOCK, DUBLIN 1, D01 YE64,
IRELAND.
Manufacturer responsible for batch release
BESINS MANUFACTURING BELGIUM SA
Groot Bijgaardenstraat 128
Drogenbos,B-1620
Belgium

This medicinal product is authorised in the Member States of the European Economic Area under the following designations:
Belgium, Denmark, Germany, France, Luxembourg, Portugal: Estreva 0.1% gel
Finland: Estrena 0.1% gel

This leaflet was last approved on: