Package Insert: Information for the User

Climodien 2 mg/2 mg Coated Tablets

estradiol valerate / dienogest

1.What is Climodien and how is it used

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

3.How to take Climodien

4.Possible adverse effects

5.Storage of Climodien

6. Contents of the package and additional information

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

Climodien is used for:

Relief of symptoms that appear after menopause

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

Medical History and Regular Check-ups

The use of THS involves risks that should be taken into account when deciding whether to start or continue treatment.

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

Before starting (or restarting) THS, your doctor will ask 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 taking Climodien, you should visit your doctor for regular check-ups (at least once a year). In these check-ups, discuss with your doctor the benefits and risks of continuing with Climodien.

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

Do not take Climodien

If any of the following cases apply to you. If you are unsure about any of the following points, consult your doctor before taking Climodien.

Do not take Climodien:

• If you have or have hadbreast canceror suspect that you may have it.
• If you have acancer sensitive to estrogens, such as endometrial cancer, or suspect that you may have it.
• If you haveabnormal vaginal bleeding.
• If you have anunusually thickened endometrium(endometrial hyperplasia) that has not been treated.
• If you have or have hada blood clot in a vein(thrombosis), such as in the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• If you have ablood clotting disorder(such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If you have or have had recently a disease caused by blood clots in the arteries, such as aheart attack, strokeorangina pectoris.
• If you have or have had aliver diseaseand your liver function tests have not returned to normal.
• If you have a rare blood disorder called “porphyria” that is inherited.
• If you areallergicto valerianate of estradiol, dienogest, or to any of the other components of this medication (including those 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 immediately.

Warnings and Precautions

Consult your doctor before starting to take Climodien.

When to be extra careful with Climodien

Before starting treatment, inform your doctor if you have ever had any of the following problems, as they may recur or worsen during treatment with Climodien. If so, you should visit your doctor more frequently for check-ups:

• Uterine fibroids
• Endometriosis (growth of the endometrium outside the uterus) or a history of excessive growth of the endometrium (endometrial hyperplasia)
• Increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)")
• Increased risk of developing 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
• Galstones
• Migraines or severe headaches
• A disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)
• Epilepsy
• Asthma
• A disease that affects the eardrum and ear (otosclerosis)
• Very high levels of fat in the blood (triglycerides)
• Fluid retention due to heart or kidney problems
• Hereditary and acquired angioedema.

Stop taking Climodien and see your doctor immediately

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

• Any of the conditions mentioned in the section “Do not take Climodien”
• Yellowing of the skin or white of the eyes (jaundice). This may be a sign of liver disease
• Swelling of the face, tongue, or throat and difficulty swallowing or urticaria accompanied by difficulty breathing, suggesting angioedema
• A significant increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• Migraine-type headaches that appear for the first time
• If you become pregnant
• If you notice signs of a blood clot, such as
• • Swollen and painful legs
  • Sudden chest pain
  • Difficulty breathing

For more information, see “Blood clots in a vein (thrombosis)”.

Note: Climodien is not a contraceptive. If you have 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.

THS and Cancer

Endometrial hyperplasia and endometrial cancer

The use of THS with estrogens alone will increase the risk of endometrial hyperplasia and endometrial cancer. The progestogen in Climodien protects against this additional risk.

Irregular bleeding

You may experience 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 taking Climodien for more than 6 months
• Continues after stopping Climodien

Consult 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 alone 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 to 17 of every 1,000 will be diagnosed with breast cancer in a 5-year period.

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

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

In women aged 50 who start HRT with estrogens alone 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. Consult your doctor if you notice any changes, such as:

• Mothers on the skin
• Changes in the nipple
• Any lump that you can see or feel

Additionally, it is recommended that you join the mammography screening programs when offered. For mammography screening, it is essential to inform the nurse/healthcare professional who performs the radiography that you are a HRT user, as these medications can increase the density of the breasts, which may affect the mammography result. When the breast density increases, the mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogens alone or with estrogen-progestogen combinations has been associated with a slightly higher risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example,in women aged 50-54 who are not using HRT,there are approximately2cases of ovarian cancer per2,000 women in a 5-year period. In women in treatment with HRT for 5 years, there are approximately3cases per2,000 patients (i.e., approximately 1 additional case).

Effect of HRT on the heart and circulation

Thrombosis

The risk ofthrombosisis approximately 1.3 to 3 times higher in HRT users compared to non-users, especially during the first year of use.

Thrombosis can be serious, and if it migrates to the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

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

• You are unable to walk for a long period due to major surgery, injury, or illness (see also section 3, “If you need to undergo surgery”)
• You have severe obesity (BMI > 30 kg/m²)
• You have a blood clotting disorder that requires long-term treatment with a medication used to prevent blood clots
• Any of your close relatives have had a blood clot in a vein, 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 your doctor immediately”.

Comparison

In women aged 50 who are not using HRT, a mean of 4 to 7 of every 1,000 will have a blood clot in a vein in a 5-year period.

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

Cardiovascular disease (heart attack)

There is no evidence that HRT prevents heart attacks.

Women over 60 years old who are using HRT with estrogen-progestogen are slightly more likely to develop cardiovascular disease than those who are not using any 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 aged 50 who are not using HRT, a mean of 8 of every 1,000 will have a stroke in a 5-year period. For women aged 50 who are taking HRT, there will be 11 cases per 1,000 users, in a 5-year period (i.e., 3 additional cases).

Other diseases

HRT does not prevent memory loss.There is some evidence of a higher risk of memory loss in women who start taking HRT after the age of 65.Ask your doctor.

Other medications and Climodien

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription, herbal remedies, or other natural products.

Your doctor will advise you.

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

• Medications forepilepsy(such as barbiturates, phenytoin, primidone, carbamazepineand possibly oxcarbazepine, topiramate, and felbamate).
• Medications fortuberculosis(such as rifampicin and rifabutin).
• Medications forinfection with the HIV virusand forinfection with theHepatitis C virus(called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such asnevirapine, efavirenz, ritonavir, and nelfinavir).
• Herbal remedies containingSt. John's Wort(Hypericum perforatum).
• Medications for thetreatment of fungal infections(such as griseofulvin, fluconazole, itraconazole, ketoconazole, and voriconazole).
• Medications for thetreatment of bacterial infections(such as clarithromycin and erythromycin).
• Medications for thetreatment of certain heart diseases, high blood pressure(such as verapamil and diltiazem).
• Orange juice.

HRT may affect the functioning of other medications:

•A medication forepilepsy(lamotrigine), as it may increase the frequency of seizures.

• Medications for theHepatitis C virus (HCV)(e.g., combination regimen for HCV, ombitasvir/paritaprevir/ritonavir with or without dasabuvir or glecaprevir/pibrentasvir) may cause elevations in liver function test results (increased ALT levels) in women using HRT with ethinylestradiol. Climodien contains estradiol instead of ethinylestradiol. It is unknown whether an increase in ALT levels can occur when Climodien is used with this HCV combination regimen.

Laboratory tests

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

Pregnancy and breastfeeding

Climodien is for use only in postmenopausal women. If pregnancy occurs, you should stop taking Climodien immediately and consult your doctor.

Driving and operating machinery

No effects on the ability to drive and operate machinery have been observed in users of Climodien.

Climodien contains saccharose, lactose, and glucose

Climodien contains saccharose, lactose, and glucose (types of sugars). If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

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.

Take this medicine exactly as your doctor has told you. Consult your doctor or pharmacist if you are unsure. Your doctor will decide for 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 pack of tablets on the day after finishing the current pack.

Do not skip between packs.

If you have been taking other THS medicines:continue until you have finished the current pack and taken all the tablets in that month. Take your first Climodien tablet the next day. Do not skip between old tablets and Climodien tablets.

If you have been using a THS treatment with a week of break:start the next 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:

A overdose may 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 Toxicological Information Service (Tel: 91 562 04 20) indicating the medicine and the amount used. It is recommended to bring the pack and leaflet to the healthcare professional.

If you forgot to take Climodien:

If you forget to take a tablet at your usual time and less than 24 hours have passed, 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 compensate for a missed tablet.

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

If you interrupt the treatment with Climodien:

You may start to feel the usual menopause symptoms again, which may 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 Climodien tablets.

If you need to undergo surgery:

If you are going to undergo surgery, inform your surgeon that you are taking Climodien. You may need to stop taking Climodien for 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 the use of this medicine, ask your doctor or pharmacist.

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

The following diseases occur more frequently in women taking THS compared to women not taking THS:

• breast cancer
• abnormal growth or cancer of the inner wall of the uterus (endometrial hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• probable memory loss if THS has been initiated after the age of 65.

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

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

Most frequent side effects:

• unexpected bleeding similar to menstruation (see also section 2 "Climodien and cancer/uterine cancer")
• breast tenderness
• breast pain

During the first months of treatment with Climodien, unexpected bleeding similar to menstruation may appear. It is usually temporary and normally disappears with continued treatment. If not, consult your doctor.

Frequent side effects(may affectup 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)
• endometrial thickening, genital inflammation, breast inflammation
• hot flashes
• weight changes, fungal infection

Rare side effects(may affectup 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
• vaginal discharge changes, breast lumps (fibrocystic disease)
• allergic reactions
• fluid retention in the legs, alteration of blood fats, increased blood glucose, changes in sexual desire, muscle cramps, anemia

Very rare side effects(may affectup to 1 in 1,000 people):

• depression
• visual disturbances
• palpitations
• indigestion, alteration of liver enzymes
• enlargement 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)

- painful red nodules on the skin (erythema nodosum)

- skin rash with circular redness or sores (erythema multiforme)

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, 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 on 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 packaging after “CAD”. The expiration date is the last day of the month indicated.

Climodien does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. Ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Composition of Climodien

Theactive principlesare estradiol valerate and dienogest. Each tablet contains 2.0 mg of estradiol valerate and 2.0 mg of dienogest.

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

Appearance of the product and contents of the packaging

Climodien tablets are round, shiny, light pink coated tablets.

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

They are available in cases with one or three blister packs.

Marketing Authorization Holder

Bayer Hispania, S.L.

Avda. Baix Llobregat, 3 - 5

08970 Sant Joan Despí (Barcelona)

Spain

Responsible for Manufacturing

Bayer Weimar GmbH und Co. KG

Doebereinerstrasse 20

99427 Weimar

Germany

This medicinal product is authorized in the member states of the European Economic Areawith the following names:

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

Last review date of this leaflet: January 2024

The detailed information of this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es.