VELBIENNE 1 mg/2 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Velbienne 1 mg/2 mg film-coated tablets EFG

Estradiol valerate and dienogest

Read this package leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Velbienne and what is it used for

Velbienneis indicated for hormone replacement therapy (HRT). It contains two types of female hormones, an estrogen and a progestogen. Velbienneis used in postmenopausal women who have had their last natural period at least 12 months ago and who still have a uterus.

Velbienneis used for:

Relief of symptoms occurring after menopause

During menopause, the amount of estrogen produced by the woman's body decreases. This can cause symptoms such as hot flashes. Velbienne relieves these symptoms after menopause. You will only be prescribed Velbienne if your symptoms seriously affect your daily life.

2. What you need to know before you take Velbienne

Medical history and regular check-ups

The use of HRT involves risks that need to be considered when deciding whether to start or continue treatment.

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

Before starting (or restarting) HRT, your doctor will ask you about your personal and family medical history. Your doctor may decide to perform a physical examination. This may include a breast examination and/or an internal examination, if necessary.

• Once you have started on Velbienne, you will need to visit your doctor for regular check-ups (at least once a year). During these check-ups, discuss with your doctor the benefits and risks of continuing with Velbienne.
• Have regular breast examinations, as recommended by your doctor.

Do not take Velbienne:

If any of the following conditions apply to you. If you are not sure about any of the following points, consult your doctorbefore taking Velbienne.

Do not take Velbienne:

• If you have or have had breast canceror if you suspect you may have it.
• If you have a cancer that is sensitive to estrogens, such as cancer of the lining of the uterus (endometrium), or if you suspect you may have it.
• If you have unusual vaginal bleeding.
• If you have an unusual thickening of the lining of the uterus(endometrial hyperplasia) that has not been treated.
• 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 a disease caused by blood clots in the arteries, such as a heart attack, stroke, or angina.
• If you have or have had a liver diseaseand your liver function tests have not returned to normal.
• If you have a rare blood disorder called porphyria that is inherited from your parents.
• If you are allergic(hypersensitive) to estrogens, progestogens, or any of the other ingredients of Velbienne (listed in section 6).
• If any of the above conditions appear for the first time while taking Velbienne, stop taking it immediately and consult your doctor immediately.

Warnings and precautions

Before starting treatment, tell your doctor if you have ever had any of the following problems, as they may come back or get worse during treatment with Velbienne. If so, you should see your doctor more often for check-ups:

• fibroids in the uterus
• growth of the lining of the uterus outside the uterus (endometriosis) or a history of excessive growth of the lining of the uterus (endometrial hyperplasia)
• increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)")
• increased risk of developing an estrogen-sensitive cancer (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
• migraine or severe headaches
• a disease that affects the immune system and many organs of the body (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• a disease that affects the eardrum and ear (otosclerosis)
• a very high level of fat in the blood (triglycerides)
• fluid retention due to heart or kidney problems
• hereditary and acquired angioedema

Stop taking Velbienne and see a doctor immediately

If you notice any of the following when taking HRT:

• any of the conditions mentioned in the section "Do not take Velbienne"
• a yellow color in the skin or the whites of the eyes (jaundice). This may be a sign of liver disease
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, along with difficulty breathing, which suggest angioedema
• a significant increase in blood pressure (symptoms may be headache, fatigue, dizziness)
• migraine-like headaches when they appear for the first time
• if you become pregnant
• if you notice signs of a blood clot, such as

• painful swelling and redness of the legs
• sudden chest pain
• difficulty breathing

For more information, see "Blood clots in a vein (thrombosis)"

Note:Velbienne is not a contraceptive. If it has been less than 12 months since your last menstrual period or if you are under 50 years old, you may need to use an additional contraceptive method to prevent pregnancy. Ask your doctor for advice.

HRT and cancer

Unusual thickening of the lining of the uterus (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial cancer)

Taking HRT with estrogens alone increases the risk of unusual thickening of the lining of the uterus (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial cancer). The progestogen in Velbienne protects against this additional risk.

Irregular bleeding

You may have irregular bleeding or spotting during the first 3-6 months of taking Velbienne. However, if irregular bleeding:

• continues for longer than the first 6 months
• starts after you have been taking Velbienne for more than 6 months
• continues after you have stopped taking Velbienne

consult your doctor as soon as possible.

Breast cancer

Evidence shows that taking hormone replacement therapy (HRT) with a combination of estrogen-progestogen or with estrogens alone increases the risk of breast cancer. The additional risk depends on how long you take HRT. The additional risk becomes apparent within 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 50-54 who are not taking HRT, on average, 13-17 out of every 1,000 will be diagnosed with breast cancer over a 5-year period.

In women aged 50 who start taking HRT with estrogen alone for 5 years, there will be 16-17 cases per 1,000 users (i.e., 0-3 additional cases).

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

In women aged 50-59 who are not taking HRT, on average, 27 out of every 1,000 will be diagnosed with breast cancer over a 10-year period.

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

In women aged 50 who start taking 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. Consult your doctor if you notice any change, such as:

• dimpling of the skin
• changes in the nipple
• any lump that you can see or feel

In addition, it is recommended that you join breast cancer screening programs when they are offered to you. For breast cancer screening, it is important that you inform the nurse/healthcare professional performing the X-ray that you are taking HRT, as these medicines may increase breast density, which can affect the outcome of the mammogram. When breast density is increased, the mammogram may not detect all lumps.

Ovarian cancer

Ovarian cancer is rare and occurs less frequently than breast cancer. The use of HRT with estrogens alone or with a combination of estrogens-progestogens has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who are not taking HRT, about 2 cases of ovarian cancer per 2,000 women are observed 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 (thrombosis)

The risk of blood clots in the veinsis approximately 1.3 to 3 times higher in HRT users compared to non-users, especially during the first year of treatment.

Blood clots can be serious and if one travels to the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

You are more likely to have a blood clot in the veins with age and if any of the following apply to you. Inform your doctor if any of these situations apply to you:

• you are unable to walk for a long time due to a major operation, injury, or illness (see also section 3, If you need to have surgery)
• you are severely overweight (BMI > 30 kg/m²)
• you have a blood clotting disorder that requires long-term treatment with a medicine used to prevent blood clots
• if any of your close relatives have ever had a blood clot in the leg, lung, or other organ
• you have systemic lupus erythematosus (SLE)
• you have cancer

For symptoms of a blood clot, see "Stop taking Velbienne and see a doctor immediately"

Comparison

In women in their 50s who are not taking HRT, it is expected that 4 to 7 out of every 1,000 will have a blood clot in a vein over a 5-year period.

In women in their 50s who have been taking HRT with estrogen-progestogen, there will be 9 to 12 cases per 1,000 users (i.e., 5 additional cases) over a 5-year period.

Heart disease (heart attack)

There is no evidence that HRT prevents a heart attack.

Women over 60 years old who are taking HRT with estrogen-progestogen are slightly more likely to develop heart disease than those who are not taking HRT.

Stroke

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

Comparison

In women in their 50s who are not taking HRT, it is expected that 8 out of every 1,000 will have a stroke over a 5-year period. For women in their 50s who are taking HRT, there will be 11 cases per 1,000 users over a 5-year period (i.e., 3 additional cases).

Other diseases

• HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start taking HRT after the age of 65. Ask your doctor for advice.

Using Velbienne with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription, herbal remedies, or other natural products. Your doctor will advise you.

Some medicines may interfere with the effect of Velbienne. This may lead to irregular bleeding. This applies to the following medicines:

• Medicines for epilepsy(such as barbiturates, primidone, phenytoin, carbamazepine, and possibly oxcarbazepine, topiramate, and felbamate)
• Medicines for tuberculosis(such as rifampicin and rifabutin)
• Medicines for HIV and hepatitis C(called protease inhibitors and reverse transcriptase inhibitors, such as nevirapine, efavirenz, ritonavir, and nelfinavir)
• Herbal remedies containing St. John's Wort(Hypericum perforatum).
• Medicines for fungal infections (such as griseofulvin, itraconazole, ketoconazole, voriconazole, and fluconazole).
• Medicines for bacterial infections (such as clarithromycin and erythromycin)
• Medicines for certain heart conditions, high blood pressure (such as verapamil and diltiazem)
• Grapefruit juice

Hormone replacement therapy may affect the performance of other medicines:

• A medicine for epilepsy (lamotrigine), as it may increase the frequency of seizures

• Medicines for hepatitis C (such as the combination of ombitasvir/paritaprevir/ritonavir with or without dasabuvir, as well as a regimen with glecaprevir/pibrentasvir) may cause increases in liver function blood test results (increase in liver enzyme ALT) in women using CHC that contains ethinylestradiol. Velbienne contains estradiol instead of ethinylestradiol. It is not known whether an increase in liver enzyme ALT can occur when using Velbienne with this combination regimen against hepatitis C. Your doctor will advise you.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription, herbal remedies, or other natural products.

Lab tests

If you need to have a blood test, tell your doctor or the laboratory staff that you are taking Velbienne, as this medicine may affect the results of some tests.

Pregnancy and breastfeeding

Velbienneis for use only in postmenopausal women. If you become pregnant, you should stop taking Velbienne immediately and consult your doctor.

Driving and using machines

No effects on the ability to drive and use machines have been observed in users of Velbienne.

Important information about some ingredients of Velbienne

Velbienne contains lactose (a type of sugar). If you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Velbienne

Your doctor will try to prescribe the lowest dose to treat your symptoms for the shortest time necessary. Consult your doctor if you think this dose is too strong or not strong enough.

Always take Velbienne exactly as your doctor has indicated. Consult your doctor or pharmacist if you are unsure. Your doctor will decide how long you should take Velbienne.

Take one tablet a day, preferably at the same time. Swallow the tablet whole with a glass of water. You can take Velbienne with or without food. Start your next calendar pack of tablets the day after you finish the current pack.

Do not take a break between packs.

If you have been taking other THS medication: continue until you have finished the current pack and have taken all the tablets for that month. Take your first Velbienne tablet the next day. Do not take a break between the old tablets and the Velbienne tablets.

If you have been using a THS treatment with a week of rest: start the day after the treatment-free period.

If this is your first THS treatment: you can start with your Velbienne tablets at any time.

If you take moreVelbiennethan you should

If you have taken too many Velbienne tablets by mistake, you may experience dizziness, vomiting, or bleeding similar to a period. No specific treatment is necessary, but you should consult your doctor or pharmacist if you are concerned.

If you forget to takeVelbienne

If you forget to take a tablet at your usual time and less than 24 hours have passed, you should take it as soon as possible. Take the next tablet at your usual time.

If more than 24 hours have passed, leave the forgotten tablet in the pack. Continue taking the other tablets at your usual time every day. Do not take a double dose to make up for a forgotten tablet.

If you forget to take your tablet for several days, you may experience bleeding.

If you stop takingVelbienne

You may start to feel your usual menopausal symptoms again, which can include hot flashes, difficulty sleeping, nervousness, dizziness, or vaginal dryness. You will also start to lose bone mass when you stop taking Velbienne. Consult your doctor or pharmacist if you want to stop taking the Velbienne tablets.

If you need to undergo surgery

If you are going to have surgery, inform your surgeon that you are taking Velbienne. You may need to stop taking Velbienne 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, Blood clots in a vein). Consult your doctor about when you can start taking Velbienne again.

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

4. Possible side effects

Like all medications, Velbienne can cause side effects, although not everyone will experience them.

Unexpected menstruation and bleeding occur during the first months of treatment with Velbienne. It is usually temporary and normally disappears with continued treatment. If it does not, consult your doctor.

The following diseases occur more frequently in women who use THS compared to women who do not take THS:

• breast cancer
• abnormal growth or cancer of the lining of the uterus (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 THS is started after 65 years of age.

For more information on these side effects, see section 2.

The following list of side effects has been associated with the use of Velbienne:

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

• headache
• dizziness
• chest pain, vaginal bleeding, hot flashes

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

• weight gain
• insomnia, nervousness, loss of appetite leading to weight loss, aggression, depression, difficulty sleeping, reduced libido, inability to reach orgasm
• dizziness, migraine, hyperactivity, tingling
• hypertension, venous blood clot (leg pain) (see also section 2 "Velbienne and venous blood clot (venous thromboembolism)"), vein inflammation, nosebleeds
• flatulence, abdominal pain, constipation, diarrhea, dry mouth, vomiting
• gallbladder pain
• increased sweating, acne, skin itching, dry skin with red scaly patches called psoriasis
• muscle pain, leg cramps
• problems with the uterine lining, painful periods, genital itching, vaginal candidiasis
• fatigue, generalized fluid retention, facial swelling

The following side effects have been reported with other THS:

• gallbladder disease
• various skin disorders:

• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma)
• red, painful nodules on the skin (erythema nodosum)
• skin rash with red target-shaped patches or blisters (erythema multiforme)

Reporting side effects:

If you experience any side effects, consult your doctor or pharmacist. Even if they are possible side effects that are not listed in this leaflet. You can also report them directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Velbienne

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

Do not use Velbienne after the expiration date that appears on the label, packaging, and blister pack after "EXP". The expiration date is the last day of the month indicated.

Store Velbienne in its original packaging to protect it from light.

Velbienne does not require any special storage temperature.

Medications should not be thrown away in drains or trash. Deposit the packaging and medications you no longer need at the pharmacy's SIGRE point. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Velbienne

The active ingredients are estradiol valerate and dienogest. Each tablet contains 1 mg of estradiol valerate and 2 mg of dienogest.

The other ingredients are lactose monohydrate, cornstarch, pregelatinized cornstarch, povidone K30 (E1201), magnesium stearate (E572), polyvinyl alcohol (1203), titanium dioxide (E171), macrogol/PEG 3350 (E1521), talc (E553b), red iron oxide (E172), black iron oxide (E172).

Appearance ofVelbienneand package contents

The Velbienne tablets are round, film-coated tablets, pink in color.

Velbienne is supplied in packs containing 28, 3x28, and 6x28 film-coated tablets.

Not all presentations may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Exeltis Healthcare, S.L. Avenida de Miralcampo, 7.

Polígono Industrial Miralcampo.

19200 Azuqueca de Henares.

Guadalajara. Spain

Manufacturer:

Laboratorios León Farma S.A.

La Vallina s/n, Polígono Industrial Navatejera,

Villaquilambre-24193 León Spain

This medication is authorized in the EEA member states with the following names:

Date of the last revision of this leaflet: November 2023