CLIMODIEN 2/2 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Climodien 2 mg/2 mg film-coated tablets

estradiol valerate / dienogest

Contents of the pack

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

1. What is Climodien and what is it used for

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

Climodien is 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. Climodien relieves these symptoms after menopause. You will only be prescribed Climodien if your symptoms seriously affect your daily life.

2. What you need to know before you start taking Climodien

Medical history and regular check-ups

The use of HRT carries risks that need to be taken into account 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 Climodien, 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 Climodien.

• Have regular breast examinations, as recommended by your doctor.

Do not take Climodien

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

Do not take Climodien:

• 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 un-treated thickening of the lining of the uterus(endometrial hyperplasia).
• 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, strokeor 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.
• If you are allergicto estradiol valerate, dienogest or any of the other ingredients of this medicine (listed in section 6).

If any of the above conditions appear for the first time while taking Climodien, stop taking it immediately and consult your doctor without delay.

Warnings and precautions

Consult your doctor before starting Climodien.

When to be especially careful with Climodien

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 Climodien. If so, you may need to go for more frequent check-ups:

• fibroids in the uterus
• growth of the lining of the uterus outside the uterus (endometriosis) or a history of thickening 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 Climodien and see a doctor immediately

If you notice any of the following when taking HRT:

• any of the conditions listed in the "Do not take Climodien" section
• yellowing of the skin or whites of the eyes (jaundice), which may be a sign of liver disease
• swelling of the face, tongue or throat and difficulty swallowing or hives accompanied by difficulty breathing, which may indicate 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: Climodien 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

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 thickening of the lining of the uterus (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial cancer). The progestogen in Climodien protects against this extra risk.

Irregular bleeding

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

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

consult your doctor as soon as possible.

Breast cancer

Available data show that taking hormone replacement therapy (HRT) with combined estrogen-progestogen or estrogen-only therapy increases the risk of breast cancer. The additional risk depends on how long you take 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 50-54 who are not taking HRT, 13-17 out of every 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 16-17 cases per 1,000 users (i.e., 0-3 extra 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., 4-8 extra cases).

In women aged 50-59 who are not taking HRT, an average of 27 cases of breast cancer per 1,000 women will be diagnosed 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 extra 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 extra 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 to inform the nurse/healthcare professional who performs the X-ray that you are taking HRT, as these medicines may increase breast density, which can affect the result of the mammogram. When breast density is increased, the mammogram may not detect all lumps.

Ovarian cancer

Ovarian cancer is less common than breast cancer. The use of HRT with estrogen-only or combined estrogen-progestogen therapy 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 will be diagnosed over a 5-year period. In women taking HRT for 5 years, about 3 cases per 2,000 users will be diagnosed (i.e., about 1 extra 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 because of 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
• any of your close relatives have 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 Climodien 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 combined estrogen-progestogen HRT, there will be 9 to 12 cases per 1,000 users (i.e., 5 extra cases) over a 5-year period.

Heart disease (heart attack)

There is no evidence that HRT prevents heart attacks.

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

Stroke

The risk of having a stroke is approximately 1.5 times higher in HRT users compared to non-users. The number of extra 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 extra 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.

Other medicines and Climodien

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

Your doctor will inform you.

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

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

HRT may affect the performance of other medicines:

• A medicine for epilepsy(lamotrigine), as it may increase the frequency of seizures.
  • Medicines for hepatitis C virus (HCV) infection(e.g., combination treatment for HCV ombitasvir/paritaprevir/ritonavir with or without dasabuvir or glecaprevir/pibrentasvir) may cause elevations in liver function blood tests (increase in liver enzyme ALT) in women using combined hormonal contraceptives with ethinylestradiol. Climodien contains estradiol instead of ethinylestradiol. It is not known whether an increase in liver enzyme ALT can occur when using Climodien with this combination treatment for HCV.

Lab tests

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

Pregnancy and breastfeeding

Climodien is for use only in postmenopausal women. If pregnancy occurs, stop taking Climodien 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 Climodien.

Climodien contains sucrose, lactose, and glucose

Climodien contains sucrose, lactose, and glucose (types of sugars). If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Climodien

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

The recommended dose is one tablet a day, preferably at the same time. Swallow the tablet whole with a glass of water. You can take Climodien 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 Climodien tablet the next day. Do not take a break between the old tablets and the Climodien 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 Climodien tablets at any time.

If you take more Climodien than you should

An overdose can cause nausea and vomiting and irregular bleeding. No specific treatment is necessary, but you should consult your doctor if you are concerned.

If you have taken more Climodien than you should, consult your doctor or pharmacist immediately, or call the Toxicology Information Service (Tel: 91 562 04 20) indicating the medicine and the amount used. It is recommended to take the pack and leaflet to the healthcare professional.

If you forget to take Climodien

If you forget to take a tablet at your usual time and it has been less than 24 hours, 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 taking Climodien

You may start to feel your usual menopause 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 Climodien. Consult your doctor or pharmacist if you want to stop taking the Climodien tablets.

If you need to have surgery

If you are going to have surgery, inform your surgeon that you are taking Climodien. You may need to stop taking Climodien 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 Climodien again.

If you have any other questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following diseases occur more frequently in women using 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 Climodien:

Very common side effects:

• unexpected bleeding similar to a period (see also section 2 "Climodien and cancer/uterus cancer")
• breast tension
• breast pain

During the first few months of treatment with Climodien, unexpected bleeding similar to a period may occur. It is usually temporary and normally disappears with continued treatment. If it does not, consult your doctor.

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

• headache, migraine, dizziness, fatigue, anxiety, depressive mood
• high blood pressure, worsening of high blood pressure
• dizziness, abdominal pain, diarrhea, elevated gamma GT (an enzyme)
• thickening of the lining of the uterus, inflammation of the genitals, inflammation of the breasts
• hot flashes
• changes in body weight, fungal infection

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

• insomnia, nervousness
• inflammation of the veins, blood clot in the veins (leg pain), painful veins
• constipation, abdominal bloating (gas), stomach inflammation
• increased sweating, hair loss, a variety of skin disorders such as rash, eczema, and acne-like dermatitis
• changes in vaginal discharge, lumps in the breasts (fibrocystic disease)
• allergic reactions
• fluid retention in the legs, alteration of fats in the blood, increased blood glucose, changes in sexual desire, muscle cramps, anemia

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

• depression
• visual disturbances
• palpitations
• indigestion, alteration of liver enzymes
• increase in the size of fibroids
• increased appetite

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 spots in a target shape or sores (erythema multiforme)

Reporting side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are possible side effects that do not appear in this leaflet. You can also report them directly through the Spanish Medicines Surveillance System: https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Climodien

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

Do not use this medicine after the expiration date that appears on the pack after "EXP". The expiration date is the last day of the month indicated.

Climodien does not require special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Deposit the packs and medicines you no longer need at the SIGRE collection point in the pharmacy. Ask your pharmacist how to dispose of the packs and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Climodien composition

The active ingredients are estradiol valerate and dienogest. Each tablet contains 2.0 mg of estradiol valerate and 2.0 mg of dienogest.

The other ingredients are lactose monohydrate, corn starch, pregelatinized corn starch, povidone K25 (E1201), and magnesium stearate (E470b). The ingredients of the tablet coating are sucrose, liquid glucose, calcium carbonate (E170), povidone K25 (E1201), macrogol 35000, carnauba wax (E903), titanium dioxide (E171), and red iron oxide (E172).

Appearance of the product and package contents

Climodien tablets are round, shiny, pale pink film-coated tablets.

They are supplied in a blister pack with 28 tablets with the days of the week printed on the blister.

Packs with one or three blisters are available.

Marketing authorization holder

Bayer Hispania, S.L.

Avda. Baix Llobregat, 3 - 5

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer

Bayer Weimar GmbH und Co. KG

Doebereinerstrasse 20

99427 Weimar

Germany

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

Spain, Netherlands, Portugal: Climodien 2 mg/2 mg

Date of the last revision of this leaflet: January 2024

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.