Estreva

Leaflet accompanying the packaging: patient information

Estreva

Estradiol
0.1%, gel

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if you need to.
• If you have any doubts, you should consult a 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 the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What is Estreva and what is it used for

The medicine contains synthetic 17β-estradiol, which is chemically and biologically identical to human endogenous estradiol. Estradiol belongs to the group of sex hormones - estrogens.
Estreva is used in hormone replacement therapy (HRT) for the treatment of estrogen deficiency symptoms in postmenopausal women.
There is limited experience with the use of the preparation in women over 65 years of age.

2. Important information before using Estreva

When not to use Estreva:

• if the patient has hypersensitivityto estradiolor any of the other ingredients of this medicine (listed in section 6);
• if the patient currently has or has had breast canceror if there is a suspicion of it;
• if the patient has malignant estrogen-sensitive tumors, such as endometrial cancer (endometrium) or if there is a suspicion of it;
• if there are unexplained vaginal bleeding;
• if there is untreated endometrial hyperplasia;
• if the patient has or has had venous thromboembolic disease(deep vein thrombosis, pulmonary embolism);
• if the patient has blood coagulation disorders(such as protein C, protein S, or antithrombin deficiency);
• if the patient has or has recently had a disease caused by arterial thrombosis, such as myocardial infarction, stroke, or angina pectoris;
• if the patient has or has had liver diseaseand liver function tests have not returned to normal;
• if the patient has a rare hereditary blood disease called porphyria.

If any of the above factors occur for the first time while using Estreva, you should stop using the medicine immediately and contact your doctor without delay.

Warnings and precautions

Before starting Estreva, you should discuss it with your doctor or pharmacist.
Special precautions
HRT should only be used to treat menopausal symptoms that negatively affect the quality of life.
At regular intervals (at least once a year), the patient should have a check-up.
If during treatment the patient notices any changes in the breasts, they should immediately inform their doctor.
Women with an intact uterus for at least 12 days of the cycle should also take a progestogen.
In the event that any of the diseases listed below have been diagnosed, occurred in the past, and (or) worsened during pregnancy or previous hormonal treatment, the patient should be under close supervision. It should be considered that these diseases may recur or worsen during treatment with Estreva; in particular, the following should be mentioned:

• uterine fibroids
• endometriosis (endometriosis) or previous cases of endometrial hyperplasia
• thromboembolic disorders in the history or the presence of factors increasing the risk of their occurrence (see below)
• risk factors for estrogen-sensitive tumors, such as first-degree relatives with breast cancer
• hypertension
• liver function disorders (e.g., liver tumor)
• diabetes, regardless of whether it is accompanied by vascular changes or not
• gallstones
• migraine or severe headaches
• systemic lupus erythematosus (SLE)
• epilepsy
• asthma
• otosclerosis (a disease of the ear leading to deafness)
• hereditary and acquired angioedema.

The doctor will decide to discontinue treatment if contraindications occur, as well as in the following situations:

• jaundice or increasing liver function disorders
• significant increase in blood pressure
• new migraine headache
• pregnancy
• swelling of the face, tongue, and (or) throat and (or) difficulty swallowing or hives, in combination with difficulty breathing, which suggests angioedema.

HRT and malignant tumors

Endometrial hyperplasia (endometrial thickening) and endometrial cancer (endometrial cancer)

The use of only estrogen HRT increases the risk of endometrial hyperplasia and endometrial cancer. The additional use of progestogen for at least 12 days in each 28-day cycle protects the patient from this increased risk. The doctor will prescribe progestogen separately if the patient has an intact uterus. If the uterus has been removed (hysterectomy), it should be discussed with the doctor whether the use of this medicine without progestogen is safe.
In the case of women with an intact uterus who do not use HRT, on average, endometrial cancer is diagnosed in 5 out of 1,000 women between the ages of 50 and 65.
In women between the ages of 50 and 65 with an intact uterus who use only estrogen HRT, endometrial cancer is diagnosed in 10-60 out of 1,000 women (i.e., 5 to 55 additional cases), depending on the dose and duration of treatment.

Breast cancer

Data confirm that taking hormone replacement therapy (HRT) in the form of a combination of 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. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT lasted more than 5 years.
Comparison
In the case of women between the ages of 50 and 54 who do not use HRT, breast cancer will be diagnosed in an average of 13 to 17 out of 1,000 women over a period of 5 years.
In the case of women aged 50 who start a 5-year estrogen 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 a 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 an average of 27 out of 1,000 women over a period of 10 years.
In the case of women aged 50 who start a 10-year estrogen 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 a 10-year estrogen-progestogen HRT, the number of cases will be 48 out of 1,000 patients (i.e., 21 additional cases).

• Regular breast exams should be performed. You should contact your doctor if you notice any changes such as:
• wrinkles of the skin,
• changes in the nipple area,
• any visible or palpable thickening.

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 approximately 2 out of 2,000 women. In women who have taken HRT for 5 years, it will occur in approximately 3 out of 2,000 women (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Vein thrombosis (thrombosis)

The risk of venous thrombosisis about 1.3 to 3 times higher in women using HRT, especially in the first year of treatment, than in women who do not use it. If a thrombus enters the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of venous thrombosis increases with age and depends on the presence of the following factors. You should inform your doctor if any of the following situations occur:

• the patient cannot walk for a long time due to extensive surgery, injury, or illness (see also section 3 "If surgery is necessary"),
• the patient is obese (Body Mass Index, BMI >30 kg/m2),
• the patient has blood coagulation disorders and requires long-term treatment with anticoagulant medication,
• if any close relatives have had a thrombosis in the leg, lung, or other organ,
• the patient is pregnant and (or) postpartum,
• the patient has systemic lupus erythematosus (SLE),
• the patient has cancer.

Comparison
In the case of women between the ages of 50 and 59 who do not use HRT, over a period of 5 years, venous thrombosis will probably occur in 4-7 out of 1,000 women. In women between the ages of 50 and 59 who have used combined estrogen-progestogen HRT for more than 5 years, venous thrombosis will occur in 9-12 out of 1,000 women (i.e., 5 more cases). In women between the ages of 50 and 59 with a removed uterus who have used only estrogen HRT for 5 years, thrombosis will occur in 5-8 out of 1,000 women (i.e., 1 more case).

Coronary heart disease

There is no scientific evidence to confirm that HRT can prevent myocardial infarction. Women over 60 years of age who use combined estrogen-progestogen HRT are slightly more likely to develop heart disease than women who do not use HRT.
In the case of women who have had a hysterectomy and use only estrogen therapy, there is no increased risk of heart disease.

Stroke

The risk of ischemic stroke is about 1.5 times higher in people using HRT than in those who do not use it. The number of additional cases of stroke caused by HRT increases with age.
Comparison
In the case of women between the ages of 50 and 59 who do not use HRT, over a period of 5 years, ischemic stroke will probably occur in 8 out of 1,000 women. Among women aged 50-59 who use HRT, there will be 11 such cases per 1,000 people using the therapy over 5 years (i.e., 3 more cases).

Other conditions

Estrogens can cause fluid retention in the body, so patients with heart or kidney disorders should be closely monitored. This is especially true for patients with end-stage renal failure, as they can expect an increase in the concentration of Estreva's active substances.
Women with previously diagnosed hypertriglyceridemia should be closely monitored while using estrogens, as there have been rare reports of significant increases in triglyceride levels in the blood, leading to pancreatitis.
Estrogens increase the amount of thyroid-binding globulin (TBG), which leads to an increase in the total amount of circulating thyroxine. The uptake of T3 by the resin is decreased, which reflects the increased TBG concentration. The levels of free T4 and free T3 remain unchanged. There may also be an increase in the concentration of other binding proteins in the blood, such as corticosteroid-binding globulin or sex hormone-binding globulin, which leads to an increase in the concentration of circulating corticosteroids and sex hormones, respectively. The free and biologically active levels of hormones remain unchanged. There may also be an increase in the concentration of other blood proteins (substrate for the angiotensinogen/renin system, alpha-1 antitrypsin, ceruloplasmin).
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 the age of 65 or older.

Children

Estradiol in the form of a spray or gel can be accidentally transferred from the patient's skin to other people. You should not allow other people, especially children, to come into contact with the exposed area of the patient's skin, and if necessary, cover the area after the spray (gel) has dried. If a child comes into contact with the area of the skin where estradiol has been sprayed (applied), you should wash the child's skin with soap and water as soon as possible. Due to the transfer of estradiol, small children may exhibit unexpected signs of sexual maturation (e.g., breast budding). In most cases, these symptoms disappear when the child is no longer exposed to estradiol in the form of a spray or gel.
If a child who may have been accidentally exposed to estradiol in the form of a spray or gel shows any signs or symptoms of maturation (breast development or other sexual changes), you should contact a doctor.

Estreva and other medicines

Some medicines may affect the action of Estreva. This may lead to irregular bleeding. This applies to the following medicines:

• medicines used to treat epilepsy(such as phenobarbital, phenytoin, and carbamazepine),
• medicines used to treat tuberculosis(such as rifampicin, rifabutin),
• medicines used to treat HIV infection(such as nevirapine, efavirenz, ritonavir, and nelfinavir),
• herbal preparations containing St. John's wort(Hypericum perforatum).

Hormone replacement therapy may affect the action of other medicines:

• anti-epileptic drugs (lamotrigine), as it may increase the frequency of seizures;
• combined treatment regimens for hepatitis C virus (HCV) infection using ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, using glecaprevir/pibrentasvir, or using sofosbuvir/velpatasvir/voxilaprevir (see section 4.4) may cause an increase in liver function test parameters in the blood (increased ALT enzyme activity) in women using combined hormonal contraceptives containing ethinyl estradiol. Estreva contains estradiol instead of ethinyl estradiol. It is not known whether increased ALT activity may occur when using Estreva with such a treatment regimen.

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. Your doctor will give you appropriate instructions.

Lab tests

If a blood test is necessary, you should inform your doctor or laboratory staff that you are taking Estreva, as this medicine 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, you should consult your doctor or pharmacist before using this medicine.
Estreva should not be used during pregnancy and breastfeeding.
If you become pregnant while taking Estreva, you should stop treatment and consult your doctor immediately.
Unintentional use of the medicine during pregnancy is not a reason to terminate it.
Before using the medicine, please consult your doctor or pharmacist.

Driving and using machines

No studies have been conducted on the effect of Estreva on the ability to drive and use machines.

Important information about some ingredients of Estreva

Estreva contains 30 mg of propylene glycol in each dose (0.5 g), which may cause skin irritation.
Estreva contains 225 mg of alcohol (ethanol) in each dose (0.5 g), which may cause a burning sensation when applied to damaged skin.

3. How to use Estreva

This medicine should always be used as directed by your doctor. If you have any doubts, you should consult your doctor or pharmacist.
Do not allow others to touch the area of the skin where the spray or gel has been applied until it has dried, and if necessary, cover it with clothing.

Dosage

Each press of the dosing pump (a dose of the medicine) delivers 0.5 g of gel.
The average dose is 1.5 g of gel, i.e., 3 doses of the medicine once a day for 24 to 28 days.
When using a daily dose of 1.5 g, a 50 g container is sufficient for a month.
The gel should be applied once a day, in the morning or evening, preferably after a bath.
The dose can be adjusted to individual needs.
Individual daily doses may range from 0.5 g to 3 g of gel.
When starting and continuing treatment for menopausal symptoms, it is recommended to use the minimum effective dose for the shortest possible period.
Women with an intact uterus should take a progestogen for at least 12 to 14 days of the cycle in combination with Estreva to avoid estrogen-induced endometrial hyperplasia.
It is not recommended to add a progestogen when treating women who have had a hysterectomy, unless endometriosis has been previously diagnosed.
Two therapeutic regimens can be used:

• 1) Cyclical: Estreva is used for 24 to 28 days, followed by a 2 to 7-day break. In women with an intact uterus, progestogen should be administered for at least the last 12 days of estrogen treatment. During the period without medication, withdrawal bleeding may occur.
• 2) Continuous: Estreva is used continuously, without breaks. In women with an intact uterus, progestogen should be administered for at least 12 days a month. During the period of progestogen withdrawal, withdrawal bleeding may occur. Continuous treatment can be recommended in cases where severe estrogen deficiency symptoms occur during the medication-free period.

How to apply Estreva 0.1% gel?

1/
Remove the cap.
2/
Holding the container with one hand, place the other hand under the pump nozzle and press the pump to obtain a dose of gel. When using it for the first time, it may be necessary to press the pump several times to start the device and obtain the first dose of gel. This dose may not have the proper volume and should be discarded.
3/
Allow the pump nozzle to return to its original position between presses.
The application surface of the gel should be approximately equal to the surface of two palms. The patient applies the gel to clean, dry, and intact skin on the abdomen, thighs, arms, or shoulders, preferably after a bath in the morning or evening. The gel should not be applied to the breast skin or mucous membranes. You should avoid contact with the eyes. You do not need to rub the medicine into the skin, but it is recommended to leave it on for about 2 minutes before dressing.
The gel does not stain clothing. After applying the gel, you should wash your hands.

Using a higher dose of Estreva than recommended

If a higher dose of Estreva than recommended is used, the following may occur: nausea, vomiting, and withdrawal bleeding.

Missing a dose of Estreva

If you forget to apply the gel on a given day, you should apply it as soon as possible and continue treatment with the recommended dose.
You should not use a double dose to make up for a missed dose.
If you do not apply the gel for several days, irregular bleeding or spotting may occur.

Stopping Estreva treatment

After stopping therapy, menopausal symptoms may recur.
If you have any further doubts about using this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Estreva can cause side effects, although not everybody gets them.
Common side effects: (≥1/100 to <1>Uncommon side effects: (≥1/1000 to <1>Rare side effects: (≥1/10,000 to <1>

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should 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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Estreva

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
There are no special precautions for storage.
Do not use this medicine if you notice any signs of deterioration.
Medicines should not be disposed of via wastewater or household waste. You should 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 Estreva contains

The active substance of Estreva is estradiol. 1 g of gel contains 1.0325 mg of estradiol hemihydrate, which corresponds to 1.0000 mg of anhydrous estradiol.
Each dose delivers 0.5 g of gel, i.e., 0.5 mg of estradiol (as 0.516 mg of estradiol hemihydrate).
The excipients are: ethanol, purified water, propylene glycol, ethylene glycol monoethyl ether, carbomer polymer, tromethamine, disodium edetate.

What Estreva looks like and what the pack contains

Estreva is a clear and odorless gel.
The packaging contains a tube with 50 g of gel in a cardboard box.

Marketing authorization holder:

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

Manufacturer:

Teva Pharmaceuticals Europe B.V.
Swensweg 5
2031 GA Haarlem
Netherlands
Delpharm Drogenbos SA
Groot Bijgaardenstraat 128
Drogenbos B-1620
Belgium
To obtain more detailed information, you should contact the local representative of the marketing authorization holder at phone number: 22 307 71 66.
Date of last revision of the leaflet:July 2025