Package Insert: Information for the User

Eviana 0.5 mg/0.1 mg Film-Coated Tablets

estradiol/norethisterone acetate

Read this package insert carefully before starting to take this medication, because

it contains important information for you.

– Keep this package insert, as you may need to read it again.

– If you have any doubts, consult your doctor or pharmacist.

– This medication has been prescribed only to you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

– If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What Eviana is and for what it is used

2. What you need to know before starting to take Eviana

3. How to take Eviana

4. Possible adverse effects

5. Storage of Eviana

6. Contents of the package and additional information

Eviana is a continuous combined hormone replacement therapy (HRT). It contains two types of female hormones, an estrogen and a progestogen. Eviana is used in postmenopausal women whose last natural period occurred at least 1 year ago.

Eviana is used for:

To alleviate symptoms that occur after menopause

During menopause, the amount of estrogens produced by the woman's body decreases. This can cause symptoms such as hot flashes in the face, neck, and chest (“hot flushes”). Eviana alleviates these symptoms after menopause. Eviana will only be prescribed if the symptoms seriously hinder your daily life.

Eviana is prescribed to women who have not had a hysterectomy and whose periods ended more than 1 year ago.

The experience in treating women over 65 years old is limited.

Medical History and Regular Check-Ups

The use of THS carries risks that must be taken into account before deciding to start taking it or continue taking it.

The experience in treating women with premature menopause (due to ovarian failure or surgical intervention) is limited. If you have premature menopause, the risks of THS may be different. Consult your doctor.

Before starting (or resuming) THS, your doctor will ask you about your medical history and that of your family. They may decide to perform a physical examination, which may include a breast examination or an internal examination, if necessary.

Once you have started taking Eviana, you will need to attend regular check-ups (at least once a year). In these check-ups, you can discuss with your doctor the benefits and risks of continuing treatment with Eviana.

Attend regular breast examinations, as recommended by your doctor.

Do Not Take Eviana

If you are affected by any of the following clinical situations. If you have doubts about any of the following points, ask your doctor before taking Eviana.

Do not take Eviana:

• If you have, have had, or suspect you may havebreast cancer.

• If you have, have had, or suspect you may haveendometrial canceror other cancer dependent on estrogens.

• If you have anyunexplained vaginal bleeding.

• If you have anexcessive thickening of the uterine lining(endometrial hyperplasia) that is not being treated.

• If you have or have had anyblood clots in a vein(venous thromboembolism), either in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).

• If you have anycoagulation disorders(such as protein C deficiency, protein S deficiency, or antithrombin deficiency).

• If you have or have had any disease caused by blood clots in arteries, such asmyocardial infarction, strokeorangina pectoris.

• If you have or have had anyliver diseaseand your liver function tests have not yet normalized.

• If you have arare blood disorder called “porphyria”, which is hereditary.

• If you areallergic(hypersensitive) toestradiol,noretisterone acetateor any of the other components of Eviana (listed in section 6, "Packaging and additional information").

If any of these conditions become apparent for the first time while taking Eviana, stop treatment immediately and consult your doctor as soon as possible.

Warnings and Precautions

Before starting treatment, inform your doctor if you have ever had any of the following problems, as they may recur or worsen during Eviana treatment. If so, you will need to attend regular check-ups more frequently:

• uterine fibroids

• thickening of the uterine lining (endometriosis) or history of excessive thickening of the uterine lining (endometrial hyperplasia)

• history of blood clots (see the section "Blood clots in a vein (venous thromboembolism)")

• increased risk of developing a cancer sensitive to estrogens (such as having a mother, sister, or grandmother who has had breast cancer)

• high blood pressure

• a liver disorder, such as a benign liver tumor

• diabetes

• gallstones

• migraines or severe headaches

• a disease of the immune system that affects multiple organs of the body (systemic lupus erythematosus or SLE)

• epilepsy

• asthma

• a disease that affects the eardrum and hearing (otosclerosis)

• very high levels of fat in the blood (triglycerides)

• fluid retention due to heart or kidney problems

• a disorder in which the thyroid gland does not produce enough thyroid hormone (hypothyroidism), and you are being treated with thyroid hormone replacement therapy

• a hereditary disease that causes recurrent episodes of intense swelling (hereditary angioedema), or if you have had episodes of rapid swelling of hands, face, feet, lips, tongue, throat (airway obstruction) or digestive tract (angioedema acquired)

• lactose intolerance.

Stop treatment with Eviana and inform your doctor immediately

If you notice any of the following symptoms while taking THS:

• any of the conditions mentioned in the section "Do not take Eviana"

• yellowing of the skin or white of the eyes (jaundice). These may be symptoms of liver disease

• swelling of the face, tongue, and/or throat and/or difficulty swallowing or urticaria, along with difficulty breathing, which are indicative of angioedema

• a significant increase in blood pressure (with symptoms such as headache, fatigue, dizziness)

• migraine-type headache, which may occur for the first time

• if you become pregnant

• if you notice symptoms of a blood clot, such as:

– inflammation with pain and redness of the legs

– sudden chest pain

– difficulty breathing

For more information, see the section "Blood clots in a vein (venous thromboembolism)".

Note:Eviana is not a contraceptive. If you have had your last menstrual period less than 12 months ago or are less than 50 years old, you may still need to use a contraceptive method to prevent pregnancy. Ask your doctor for advice.

THS and Cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and endometrial cancer

THS with estrogens only increases the risk of excessive thickening of the uterine lining (endometrial hyperplasia) and endometrial cancer.

The progestogen in Eviana protects against this additional risk.

Comparison

In women aged 50-65 with an intact uterus who are not taking THS, a mean of 5 cases of endometrial cancer will be diagnosed per 1,000 women over a 5-year period.

In women with an intact uterus aged 50-65 who take THS with estrogens only, between 10 and 60 cases of endometrial cancer will be diagnosed per 1,000 users (i.e., between 5 and 55 additional cases), depending on the dose and duration of treatment.

Irregular Bleeding

You may experience irregular bleeding or blood loss (spotting) during the first 3 to 6 months of taking Eviana. However, if the irregular bleeding:

• persists beyond the first 6 months

• begins after taking Eviana for more than 6 months

• continues after stopping Eviana

you should contact your doctor as soon as possible.

Breast Cancer

The available data show that the use of hormone replacement therapy (HRT) with estrogen-progestogen combinations or with estrogens only increases the risk of breast cancer. The additional risk depends on the duration of HRT use.

The additional risk becomes apparent after 3 years of use. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT has been used for more than 5 years.

Comparison

In women aged 50-54 who are not using HRT, a mean of 13-17 of every 1,000 will be diagnosed with breast cancer over a 5-year period.

In women aged 50 who start HRT with estrogens only for 5 years, there will be between 16 and 17 cases per 1,000 users (i.e., between 0 and 3 additional cases).

In women aged 50 who start taking HRT with estrogen-progestogen for 5 years, there will be between 21 cases per 1,000 users (i.e., between 4 and 8 additional cases).

In women aged 50-59 who are not taking HRT, a mean of 27 cases of breast cancer will be diagnosed per 1,000 women over a 10-year period.

In women aged 50 who start HRT with estrogens only for more than 10 years, there will be 34 cases per 1,000 users (i.e., 7 additional cases).

In women aged 50 who start HRT with estrogen-progestogen for 10 years, there will be 48 cases per 1,000 users (i.e., 21 additional cases).

Examine your breasts regularly. Visit your doctor if you notice any changes, such as:

• dimples in the skin

• changes in the nipples

• any lump that you can see or feel.

Additionally, it is recommended that you participate in breast screening programs when offered.

In breast examinations, it is essential to inform your nurse/healthcare professional that you are taking HRT when they perform the X-ray examination, as this medication can increase breast density, which may affect the mammography result. When breast density is higher, it may be that mammography does not detect all lumps.

Endometrial Cancer

Endometrial cancer is less common than breast cancer. The use of HRT with estrogens alone or with estrogen-progestogen combinations has been associated with a slightly higher risk of endometrial cancer.

The risk of endometrial cancer varies with age. For example, in women aged 50-54 who are not taking HRT, approximately 2 cases of endometrial cancer will be diagnosed per 2,000 women over a 5-year period. In women taking HRT for 5 years, approximately 3 cases will be diagnosed per 2,000 patients (i.e., approximately 1 additional case).

Effect of HRT on the Heart and Circulation

Vein Thromboembolism

The risk ofvein thromboembolismis approximately 1.3 to 3 times higher in HRT users than in non-users, especially during the first year.

Vein thromboembolism can be serious, and if one of them reaches the lungs, it can cause chest pain, difficulty breathing, syncope, or even death.

The probability of developing vein thromboembolism will be higher with increasing age and if any of the following factors are present. If any of these situations may apply to you, inform your doctor:

• you will be unable to walk for a long time due to a major surgical operation, injury, or illness (see also section 3, "If you are to undergo surgery")

• you have significant obesity (BMI > 30 kg/m2)

• you have a coagulation disorder that requires prolonged treatment with medication to prevent clots

• a close relative has had a blood clot in the legs, lungs, or other organs

• you have lupus erythematosus (LES)

• you have cancer.

To know the symptoms of a blood clot, see the section "Stop treatment with Eviana and inform your doctor immediately".

Comparison

It is estimated that, over a 5-year period, a mean of 4-7 of every 1,000 women in their 50s who are not taking HRT will develop a vein thromboembolism.

In women in their 50s who take HRT with estrogen-progestogen for 5 years, there will be between 9 and 12 cases per 1,000 users (i.e., 5 additional cases).

Cardiovascular Diseases (Myocardial Infarction)

HRT has not been shown to prevent myocardial infarction. Women over 60 who use HRT with estrogen-progestogen have a slightly higher risk of developing cardiovascular disease than those who do not take HRT.

Stroke

The risk of stroke is approximately 1.5 times higher in HRT users than in non-users. The number of additional stroke cases due to HRT use will increase with age.

Comparison

It is estimated that, over a 5-year period, a mean of 8 of every 1,000 women in their 50s who are not taking HRT will develop a stroke.

In women in their 50s who are taking HRT, the number of cases will be 11 per 1,000 users over a 5-year period (i.e., 3 additional cases).

Other Disorders

HRT does not prevent memory loss. There are indications of a higher risk of memory loss in women who start using HRT after the age of 65. Ask your doctor for advice.

Use with Other Medications

Some medications may interfere with the effect of Eviana. This may cause irregular bleeding.

Such medications include:

•Medications forepilepsy(such as phenobarbital, phenytoin, and carbamazepine)

•Medications fortuberculosis(such as rifampicin and rifabutin)

•Medications forinfection with HIV(such as nevirapine, efavirenz, ritonavir, and nelfinavir)

•Medications forhepatitis C(such as telaprevir)

•Preparations based on plants containingSt. John's Wort(Hypericum perforatum).

.

HRT may affect the functioning of certain medications:

•Medication for epilepsy (lamotrigine), which may increase the frequency of seizures.

•Medications for hepatitis C virus (HCV) (such as the combination regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir, as well as a regimen with glecaprevir/pibrentasvir) may cause increases in liver function test results (elevated ALT levels) in women taking combined hormonal contraceptives (CHCs) containing ethinylestradiol. Eviana contains estradiol instead of ethinylestradiol. It is unknown whether this may cause an increase in ALT levels when using Eviana with this HCV regimen.

Other medications may increase the effects of Eviana:

•Medications containingketoconazole(a fungicide).

Eviana may affect concomitant treatment with ciclosporin.

Inform your doctor or pharmacistif you are taking or have recently taken any other medication, including those purchased without a prescription, those made from medicinal plants, or other natural products. Your doctor will advise you.

Laboratory Tests

If you need a blood test, inform your doctor or laboratory staff that you are taking Eviana, as this medication may alter the results of some laboratory parameters.

Taking Eviana with Medications and Beverages

The tablets can be taken with or without food or beverages.

Pregnancy and Breastfeeding

Pregnancy:Eviana should only be used in postmenopausal women. If you become pregnant, stop taking Eviana and contact your doctor.

Breastfeeding:Do not take Eviana if you are breastfeeding.

Driving and Operating Machinery

Eviana has no known effects on the ability to drive or operate machinery.

Important Information about Some Components of Eviana:

Eviana contains lactose monohydrate. If you have a certain sugar intolerance, consult your doctor before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor.

In case of doubt, consult your doctor or pharmacist.

Take one tablet once a day, approximately at the same hour every day.Take the tablet with a glass of water.

Take one tablet every day without interruption.After taking the 28 tablets from the calendar blister pack, you should continue with a new one.

For more information on the use of the calendar blister pack, see USER INSTRUCTIONS at the end of this leaflet.

You canstart treatment with Evianaany day of the week. However, if you have changed from another THS product with which you had menstrual bleeding, start the new treatment just after finishing the bleeding.

Your doctor should prescribe the lowest effective dose and for the shortest time possible that will provide relief from symptoms. Talk to your doctor if you think the dose is excessive or insufficient.

If you take more Eviana than you should

If you have taken more Eviana than you should, consult your doctor or pharmacist as soon as possible. Taking more estrogens than prescribed by your doctor may cause breast tenderness, nausea, vomiting, and/or irregular vaginal bleeding (metrorrhagia). Taking more progestogens than prescribed by your doctor may cause depressive mood, fatigue, acne, and excessive hair growth on the body or face (hirsutism).

If you forgot to take Eviana

If you have forgotten to take the tablet at the usual time, take it within the next 12 hours. If more than 12 hours have passed, take it the next day at the usual time. Do not take a double dose to compensate for the missed dose.

Missing a dose may increase the likelihood of experiencing intercurrent bleeding and spotting, unless you have had a hysterectomy.

If you interrupt treatment with Eviana

If you want to interrupt treatment with Eviana, talk to your doctor first, who will explain the effects of interrupting treatment and discuss other possibilities with you.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

If you must undergo surgery

If you are to undergo a surgical procedure, inform the surgeon that you are taking Eviana. You may need to stop taking Eviana for 4 to 6 weeks before the operation to reduce the risk of blood clots (see the section "Blood clots in a vein (thromboembolism)", in section 2). Ask your doctor when you can start taking Eviana again.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following disorders have been reported more frequently in women using THS compared to those not using it:

•breast cancer

•abnormal growth or cancer of the lining of the uterus (endometrial hyperplasia or endometrial cancer)

•ovarian cancer

•blood clots in the veins of the legs or lungs (venous thromboembolism)

•cardiovascular disease

•stroke

•probable memory loss if THS is started at an age of over 65 years.

To obtain more information about these side effects, see Section 2, “What you need to know before starting to take Eviana”.

Very common side effects (may affect more than 1 in 10 people)

• Vaginal bleeding.

Common side effects (may affect up to 1 in 10 people)

•Vaginal infection by fungi or vaginal inflammation

•Excessive growth of the lining of the uterus (endometrial hyperplasia)

•Nausea

•Abdominal pain (stomach)

•Back or neck pain

•Pain in the arms or legs

•Headache.

Uncommon side effects (may affect up to 1 in 100 people)

•Allergic reactions (hypersensitivity)

•Depression or worsening of existing depression

•Nervousness

•Dizziness

•Migraines (see the section “Stop taking Eviana”, in Section 2)

•Pain or discomfort in the breasts

•Abdominal inflammation or distension (stomach)

•Weight gain due to fluid retention

•Swelling of arms and legs (peripheral edema)

•Cramps in the legs

•Acid reflux (dyspepsia)

•Acne

•Hair loss (alopecia)

•Itching or urticaria.

Very rare side effects (may affect up to 1 in 10,000 people)

•Generalized hypersensitivity reactions (e.g., anaphylactic reaction or anaphylactic shock) have been reported.

Other side effects of combined HRT

•Biliary tract disease

•Diverse skin disorders:

– skin pigmentation, especially on the face and neck, known as “pregnancy spots” (chloasma)

– red and painful skin nodules (erythema nodosum)

– rash with ulcers or redness in the shape of a target (erythema multiforme)

– red or purple discoloration of the skin and/or mucous membranes (vascular purpura)

•Dry eyes

•Changes in tear composition.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the outer packaging, after “CAD”. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25 °C. Do not refrigerate.

Keep the container in the outer packaging to protect it from light.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Eviana Composition

- The active principles of Eviana are estradiol and noretisterone acetate. Each tablet contains 0.5 mg of estradiol (as hemihydrate of estradiol) and 0.1 mg of noretisterone acetate.

- The other components are: lactose monohydrate, cornstarch, hydroxypropyl cellulose, magnesium stearate, hypromellose, triacetin, and talc.

Appearance of the product and contents of the package

Coated tablets, white, round, with a diameter of 6 mm. On one side, "NOVO 291" is engraved, and on the other, the Novo-Nordisk logo (a bee).

Presentation:

•28 coated tablets with a blister pack

•3 x 28 coated tablets with a blister pack

Only some package sizes may be commercially available.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Isdin S.A.

Provençals 33

Barcelona 08019

Spain

Manufacturer:

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark

This medicine is authorized in the Member States of the European Economic Area with the following names:

Activelle: Austria, Portugal

Activelle low: Denmark, Iceland, Italy

Activelle minor: Belgium, Luxembourg

Eviana: Estonia, Hungary, Netherlands, Norway, Spain, Sweden

Noviana: Finland

Last review date of this leaflet:September 2024

Other sources of information

The detailed information on this medicine is available on the website of{country name/agency}:

USER INSTRUCTIONS

How to use the calendar blister pack

1. Place the day indicator

Turn the inner disc and fix the day of the week in front of the closed opening with a plastic latch.

2. How to take the first tablet

Break the plastic latch and take the first tablet.

3. Move the dial every day

Simply turn 1 space the transparent disc in the direction of the clock hands, as indicated by the arrow. Take the next tablet. Remember to take only 1 tablet a day.

The transparent disc can only be turned once the corresponding tablet has been taken.