Eviana 0.5 mg/0.1 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Eviana 0.5 mg/0.1 mg film-coated tablets

estradiol/norethisterone acetate

Read the entire leaflet carefully before you start taking 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 pass it on to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Eviana is and what it is used for

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

Eviana is used for:

Relieving symptoms occurring after menopause

During menopause, the amount of oestrogen produced by a woman's body decreases. This may cause symptoms such as heat in the face, neck and chest ("hot flushes"). Eviana relieves these postmenopausal symptoms. Eviana will only be prescribed to you if these symptoms seriously affect your daily life.

Eviana is prescribed to women who have not had a hysterectomy and whose periods have stopped for more than one year.

Experience with treatment in women over 65 years of age is limited.

2. What you need to know before starting Eviana

Medical history and periodic check-ups

The use of HRT carries risks that must be considered before deciding to start or continue taking it.

Experience in treating women with premature menopause (due to ovarian failure or surgical intervention) is limited. If you have premature menopause, the risks of HRT may differ. Please consult your doctor.

Before starting (or restarting) HRT, your doctor will ask about your personal and family medical history. They may decide to perform a physical examination, which could include a breast examination or an internal pelvic exam, if necessary.

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

Have regular breast examinations as recommended by your doctor.

Do not take Eviana

If any of the following clinical conditions apply to you. If you have any doubts about any of the points below, ask your doctor before taking Eviana.

Do not take Eviana:

• If you currently have, have had, or suspect you may have breast cancer.
• If you currently have, have had, or suspect you may have cancer of the lining of the womb (endometrial cancer) or any other estrogen-dependent cancer.
• If you experience vaginal bleeding of unknown cause.
• If you have excessive thickening of the lining of the womb (endometrial hyperplasia) that is not being treated.
• If you currently have or have ever had blood clots in a vein (venous thromboembolism), either in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• If you have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency).
• If you currently have or have had arterial diseases 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 yet returned to normal.
• If you have a rare inherited blood disorder called "porphyria".
• If you are allergic (hypersensitive) to estradiol, norethisterone acetate, or any of the other ingredients of Eviana (listed in section 6, "Contents of the pack and other information").

If any of these conditions develops for the first time while you are taking Eviana, stop treatment immediately and contact your doctor as soon as possible.

Warnings and precautions

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 Eviana. If so, you should have more frequent check-ups:

• Uterine fibroids
• Thickening of the lining of the womb (endometriosis) or history of excessive thickening of the lining of the womb (endometrial hyperplasia)
• History of blood clots (see section “Blood clots in a vein (venous thromboembolism)”)
• Increased risk of estrogen-sensitive cancers (such as having 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 or SLE)
• Epilepsy
• Asthma
• A condition affecting 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 does not produce enough thyroid hormone (hypothyroidism), and you are being treated with thyroid hormone replacement therapy
• A hereditary condition causing recurrent episodes of severe swelling (hereditary angioedema), or if you have experienced episodes of rapid swelling of the hands, face, feet, lips, tongue, throat (airway blockage), or digestive tract (acquired angioedema)
• Lactose intolerance

Stop taking Eviana and contact your doctor immediately

If you experience any of the following symptoms while taking HRT:

• Any of the conditions listed under “Do not take Eviana”
• Yellowing of the skin or whites of the eyes (jaundice). These may be symptoms of liver disease
• Swelling of the face, tongue and/or throat and/or difficulty swallowing or hives, together with difficulty breathing, which are symptoms of angioedema
• A large 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:
  • Swelling, pain and redness in 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 less than 12 months have passed since your last menstrual period or you are under 50 years of age, you may still need to use a contraceptive method to prevent pregnancy. Seek advice from your doctor.

HRT and cancer

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

Estrogen-only HRT increases the risk of excessive thickening of the womb lining (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer).

The progestogen in Eviana protects against this additional risk.

Comparison:

In women aged 50 to 65 years with an intact uterus who do not take HRT, an average of 5 cases of endometrial cancer will be diagnosed per 1,000 women.

In women aged 50 to 65 years with an intact uterus who take estrogen-only HRT, 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 spotting during the first 3 to 6 months of taking Eviana. However, if irregular bleeding:

• Persists beyond the first 6 months
• Begins after having taken Eviana for more than 6 months
• Continues after stopping Eviana

you should contact your doctor as soon as possible.

Breast cancer

Available data show that the use of hormone replacement therapy (HRT), whether combined estrogen-progestogen or estrogen-only, increases the risk of breast cancer. The additional risk depends on how long you use HRT.

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 you have used HRT for more than 5 years.

Comparison:

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

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

In women aged 50 to 59 years not taking HRT, an average of 27 cases of breast cancer will be diagnosed per 1,000 women over a 10-year period.

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

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

• Dimpling of the skin
• Changes in the nipples
• Any lump you can see or feel.

In addition, it is advisable to participate in breast screening programs when offered.

During breast examinations, it is important to inform your nurse/healthcare professional that you are taking HRT when undergoing X-ray imaging, as this medicine may increase breast density, which can affect the results of a mammogram. When breast density is higher, mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer is less common than breast cancer. The use of estrogen-only HRT or combined estrogen-progestogen HRT has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 years not using HRT, about 2 cases of ovarian cancer are observed per 2,000 women over a 5-year period. In women taking HRT for 5 years, about 3 cases per 2,000 patients are observed (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in a vein (venous thromboembolism)

The risk of blood clots in veins is approximately 1.3 to 3 times higher in HRT users than in non-users, especially during the first year.

Venous blood clots can be serious, and if a clot travels to the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

The likelihood of developing venous blood clots increases with age and if any of the following factors apply. If any of these situations may apply to you, inform your doctor:

• Inability to walk for prolonged periods due to major surgery, injury, or illness (see also section 3, “If you are undergoing surgery”)
• Significant overweight (BMI > 30 kg/m²)
• Blood clotting disorder requiring long-term anticoagulant treatment
• Close family history of blood clots in legs, lungs, or other organs
• Systemic lupus erythematosus (SLE)
• Cancer

For symptoms of a blood clot, see the section “Stop taking Eviana and contact your doctor immediately”.

Comparison:

It is estimated that, over a 5-year period, an average of 4 to 7 out of 1,000 women in their fifties who do not take HRT will experience a venous blood clot.

In women in their fifties taking combined estrogen-progestogen HRT for 5 years, there will be between 9 and 12 cases per 1,000 users (i.e., 5 additional cases).

Heart disease (myocardial infarction)

HRT has not been shown to prevent heart attacks. Women over 60 years of age who use combined estrogen-progestogen HRT have a slightly higher risk of developing heart disease than those not taking 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 increases with age.

Comparison:

It is estimated that, over a 5-year period, an average of 8 out of 1,000 women in their fifties who do not take HRT will suffer a stroke.

In women in their fifties 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 is evidence of an increased risk of memory loss in women who start HRT after age 65. Seek advice from your doctor.

Use with other medicines

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

Such medicines include:

• Medicines for epilepsy (such as phenobarbital, phenytoin, and carbamazepine)
• Medicines for tuberculosis (such as rifampicin and rifabutin)
• Medicines for HIV infection (such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• Medicines for hepatitis C (such as telaprevir)
• Herbal preparations containing St. John’s wort (Hypericum perforatum)

HRT may affect the function of certain medicines:

• Epilepsy medicine (lamotrigine), as it may increase seizure frequency.
• Medicines for hepatitis C virus (HCV) (such as the combination regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir, and the regimen glecaprevir/pibrentasvir) may cause increases in liver function blood test results (elevated liver enzyme ALT) in women using combined hormonal contraceptives (CHCs) containing ethinylestradiol. Eviana contains estradiol instead of ethinylestradiol. It is unknown whether elevated ALT liver enzyme levels may occur when using Eviana with this HCV combination regimen.

Other medicines may increase the effects of Eviana:

• Medicines containing ketoconazole (an antifungal).

Eviana may affect concomitant treatment with cyclosporine.

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription, herbal medicines, or other natural products. Your doctor will advise you.

Blood tests

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

Taking Eviana with food and drinks

Tablets can be taken with or without food or drinks.

Pregnancy and breastfeeding

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

Breastfeeding: You should not take Eviana if you are breastfeeding.

Driving and using machines

Eviana has no known effects on the ability to drive or use machines.

Important information about some of the ingredients of Eviana:

Eviana contains lactose monohydrate. If you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Eviana

Follow exactly the instructions for taking this medicine as given by your doctor.

If in doubt, consult your doctor or pharmacist.

Take one tablet once daily, at approximately the same time each day. Swallow the tablet with a glass of water.

Take one tablet every day without interruption. After taking all 28 tablets from the calendar blister pack, you must start a new pack immediately.

For more information on how to use the calendar pack, see DIRECTIONS FOR THE USER at the end of this leaflet.

You may start treatment with Eviana on any day of the week. However, if you are switching from another HRT product that caused menstrual bleeding, begin the new treatment immediately after the bleeding has stopped.

Your doctor should prescribe the lowest effective dose for the shortest duration necessary to relieve your symptoms. Talk to your doctor if you think the dose is too high or too low.

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 depressed mood, fatigue, acne, and increased growth of body or facial hair (hirsutism).

If you forget to take Eviana

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

Missing a dose may increase the likelihood of breakthrough bleeding or spotting, unless you have had your uterus removed.

If you stop taking Eviana

If you wish to stop treatment with Eviana, speak to your doctor first. Your doctor will explain the effects of stopping treatment and discuss alternative options with you.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

If you are due to have surgery

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

4. Possible side effects

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 HRT compared to women who do not use HRT:

• breast cancer
• abnormal growth or cancer of the lining of the womb (endometrial hyperplasia or endometrial 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 more information about these side effects, see section 2, “What you need to know before taking 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)

• Fungal infection of the genital area or vaginal inflammation
• Excessive growth of the lining of the womb (endometrial hyperplasia)
• Nausea
• Abdominal (stomach) pain
• 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
• Migraine (see the section “Stop treatment with Eviana” in section 2)
• Breast pain or discomfort
• Swelling or bloating of the abdomen (stomach)
• Weight gain due to fluid retention
• Swelling of the arms and legs (peripheral oedema)
• Leg cramps
• Indigestion (dyspepsia)
• Acne
• Hair loss (alopecia)
• Itching or hives.

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

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

Other side effects of combined HRT

• Gallbladder disease
• Various skin disorders:
  • skin pigmentation, especially on the face and neck, known as “pregnancy mask” (chloasma)
  • red, painful skin nodules (erythema nodosum)
  • rash with ulcers or target-shaped redness (erythema multiforme)
  • red or purple discolouration of the skin and/or mucous membranes (vascular purpura)
• Dry eyes
• Changes in tear composition.

Reporting of side effects

If you experience any side effect, talk to your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Eviana

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

Do not use this medicine after the expiry date stated on the label and on the outer packaging, following "EXP". The expiry date is the last day of the month indicated.

Do not store above 25 °C. Do not refrigerate.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Eviana

• The active substances in Eviana are estradiol and norethisterone acetate. Each tablet contains 0.5 mg of estradiol (as estradiol hemihydrate) and 0.1 mg of norethisterone acetate.
• The other components are: monohydrate lactose, corn starch, hydroxypropyl cellulose, magnesium stearate, hypromellose, triacetin, and talc.

Appearance of the product and contents of the pack

Film-coated tablets, white, round, 6 mm in diameter. One side is engraved with “NOVO 291” and the other side bears the Novo-Nordisk logo (an Apis bull).

Pack sizes:

• 28 film-coated tablets
• 3 x 28 film-coated tablets

Only certain pack sizes may be marketed.

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 medicinal product is authorized in the European Economic Area member states under the following names:

Activelle: Austria, Portugal

Activelle low: Denmark, Iceland, Italy

Activelle minor: Belgium, Luxembourg

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

Noviana: Finland

Date of the most recent review of this leaflet: September 2024

Other sources of information

Detailed information on this medicinal product is available on the website of {name of Member State/Agency}:

INSTRUCTIONS FOR THE USER

How to use the calendar blister pack

1. Set the day indicator

Rotate the inner disc to align the day of the week with the opening covered by a plastic tab.

2. How to remove the first tablet

Break the plastic tab and remove the first tablet.

3. Move the dial each day

Simply rotate the transparent disc one space clockwise, as indicated by the arrow. Remove the next tablet. Remember to take only one tablet per day.

The transparent disc can only be advanced after the corresponding tablet has been removed.