PROGYNOVA 1 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Progynova 1 mg Coated Tablets

Estradiol Valerate

Contents of the Package Leaflet:

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

1. What is Progynova and what is it used for

Progynova is a hormonal medicine.

This medicine is indicated for hormone replacement therapy (HRT) for:

treatment of menopausal symptoms (the period of time when reproductive function and menstruation cease in a woman), natural or surgically induced (castration), e.g. hot flushes, night sweats, urogenital disorders (atrophic vulvovaginitis).

If you have an intact uterus, the administration of estrogens, such as Progynova, should always be accompanied by the sequential administration of a progestogen.

Progynova should not be used to prevent heart disease or to increase intellectual capacity.

Progynova is not a contraceptive and does not restore fertility.

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

Follow your doctor's instructions carefully.

Read the following information before using Progynova.

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 resuming) HRT, 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 treatment with Progynova, you should visit your doctor for regular check-ups (at least once a year). During these check-ups, discuss the benefits and risks of continuing Progynova with your doctor.

Regular breast examinations should be performed, as recommended by your doctor.

Do not take Progynova

if any of the following conditions apply to you. If you are unsure about any of the following points, consult your doctorbefore taking Progynova. Do not take Progynova:

• If you are pregnant or think you may be pregnant or if you are breastfeeding.
• If you have or have had breast canceror if you suspect you may have it.
• If you have known or suspected pre-malignant lesionsinfluenced by sex hormones.
• If you have a cancer that depends on the action of estrogens, such as cancer of the lining of the uterus (endometrium) or suspect you may have it.

• If you have abnormal vaginal bleeding.

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

• If you have or have had a blood clot in a vein(thrombosis), e.g. in the legs (deep vein thrombosis) or lungs (pulmonary embolism).

• If you have any condition that affects blood clotting(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 (arterial thrombosis), (e.g. angina, heart attack, stroke).

• If you have or have had any liver disorder, and liver function tests have not returned to normal.
• If you have a rare blood disorder called porphyria that is inherited from parents to children (hereditary).
• If you have sickle cell anemia (a blood disease).

• If you are allergicto estradiol valerateor any of the other components of this medicine (listed in section 6).

If any of these diseases occur for the first time while you are taking Progynova, stop treatment and consult your doctor immediately.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Progynova.

Visit your doctor regularly and at least once a year. Discuss with your doctor at each visit the need to adjust or continue treatment. Your doctor will check if you have a high risk of developing thrombosis due to a combination of risk factors or a very high risk factor. In the case of a combination of risk factors, the risk may be higher than a simple addition of 2 individual risks. If the risk is too high, your doctor will not prescribe HRT.

For the treatment of menopausal symptoms, HRT should only be started when symptoms affect the quality of life of the woman. In all cases, a careful assessment of the risks and benefits should be made at least annually, and HRT should only be continued as long as the benefits outweigh the risks. The lowest effective dose and the shortest duration of treatment should always be considered.

When taking special precautions with Progynova

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

• Gynecological disorders of any kind, such as irregular, frequent, or persistent uterine bleeding, fibroids (a type of uterine tumor), endometriosis (appearance of tissue that lines the uterus outside its usual location), or a history of endometrial hyperplasia (abnormal multiplication of cells that line the inside of the uterus).
• Increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)").
• Increased risk of developing a cancer that depends on the action of estrogens (e.g. having a mother, sister, or grandmother who has had breast cancer).

• Changes or alterations in the breasts.

• High levels of certain fats (triglycerides) in the blood or a family history of this condition due to the risk of developing pancreatitis (inflammation of the pancreas).
• Fluid retention due to heart or kidney problems.

• High blood pressure.

• Liver disorders, such as a benign liver tumor.
• Kidney disorders.

• Diabetes.

• Gallstones.

• Migraines or severe headaches.

• Systemic lupus erythematosus (a disease that affects many organs of the body).

• Epilepsy.

• Multiple sclerosis (a disease of the nervous system).

• Asthma.

• Itching (pruritus).

• Otosclerosis (abnormal bone growth in the ear), a disease that affects the eardrum and ear.

• Chorea minor (a disease of the nervous system).

• Hypercalcemia (elevated calcium levels in the blood).
• Hereditary and acquired angioedema.

Be careful not to exceed the recommended doses.

During treatment with HRT, some serious diseases may occur more frequently, such as blood clots (thrombosis) and some types of tumors.

Stop taking Progynova and go to the doctor immediately

If you notice any of the following disorders when taking HRT:

• any of the disorders mentioned in the section "Do not take Progynova",
• yellowing of the skin or whites 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, 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 symptoms of a blood clot, see "Stop taking Progynova and go to the doctor immediately"

Note: Progynova 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 still need to use an additional contraceptive method to prevent pregnancy. Ask your doctor for advice.

HRT and cancer

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

HRT with estrogen alone increases the risk of excessive thickening of the lining of the uterus (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial cancer).

Taking a progestogen in addition to estrogen for at least 12 days per 28-day cycle protects you from this increased risk. If you still have your uterus, your doctor will prescribe another hormone, a progestogen, to reduce the risk of uterine cancer.

If you no longer have your uterus (you have had a hysterectomy), consult your doctor about the safe use of this medicine without a progestogen.

In women with an intact uterus who do not use HRT, an average of 5 out of 1,000 women, aged 50-65, will be diagnosed with endometrial cancer. In women with an intact uterus who use HRT with estrogen alone, between 10 and 60 out of 1,000 women, aged 50-65, will be diagnosed with endometrial cancer (i.e., between 5 and 55 additional cases), depending on the dose and duration of treatment.

Unexpected bleeding

You will have menstrual bleeding once a month (also called withdrawal bleeding) while taking Progynova. However, if you have unexpected bleeding or spotting in addition to your menstrual period, which:

• continues for longer than the first 6 months;
• starts after you have been taking Progynova for more than 6 months;
• continues after you have finished treatment with Progynova;

consult your doctor as soon as possible.

Breast cancer

Existing data show that the use of hormonal replacement therapy (HRT) with combined estrogen-progestogen or estrogen-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.

Your doctor will guide you on how to detect abnormalities in your breast and will perform periodic check-ups throughout treatment.

For women who do not have a uterus and are using HRT with estrogen alone for 5 years, there is little or no increase in the risk of breast cancer.

Comparison

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

In women aged 50 who start HRT with estrogen alone for 5 years, there will be between 16 and 17 cases per 1,000 women 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 women users (i.e., between 4-8 cases).

In women aged 50-59 who are 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 HRT with estrogen alone for more than 10 years, there will be 34 cases per 1,000 women 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).

Check your breasts regularly. Consult your doctor if you detect any changes 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 participate in breast cancer screening programs when offered. For breast cancer screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are taking HRT, as these medications can increase breast density, which can affect the result of the mammogram. When breast density increases, the mammogram may not detect all lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogen alone or combined estrogen-progestogen 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, there are approximately 2 cases of ovarian cancer per 2,000 women over a 5-year period. In women taking HRT for 5 years, there are approximately 3 cases per 2,000 patients (i.e., approximately 1 additional case).

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)

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

Blood clots can be serious and, if one travels to the lungs, 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 major surgery, injury, or illness (see also section 3, If you need to have surgery)
• You have severe obesity (Body Mass Index >30 kg/m2)
• You have blood clotting problems that require long-term treatment to prevent blood clots
• Any of your close relatives have had a blood clot in the leg, lung, or any other organ
• You have systemic lupus erythematosus (SLE)
• You have cancer.

For symptoms of a blood clot, see "Stop taking Progynova and go to the doctor immediately"

Comparison

In women in their 50s who are not taking HRT, it is expected that an average of 4 to 7 out of 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 for 5 years, there will be 9 to 12 cases per 1,000 users (i.e., 5 additional cases).

For women in their 50s who do not have a uterus and have been taking HRT with estrogen alone for 5 years, there will be 5 to 8 cases per 1,000 users (i.e., 1 additional case).

Blood clots also occur, although much less frequently, in the arteries of the heart (heart attack, angina), in the arteries of the brain (stroke), or in the eyes (vision loss or double vision).

Coronary heart disease (heart attack)

HRT has not been shown to prevent heart attacks.

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

The risk of developing cardiovascular disease does not increase in women without a uterus who take estrogen-only therapy.

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 increases with age.

Comparison

In women in their 50s who are not taking HRT, it is expected that an average of 8 out of 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).

Liver tumors

Rarely, liver tumors have been observed after the use of hormonal substances such as those contained in Progynova.

Other diseases

Tell your doctor if you have a kidney or heart function disorder. Estrogens can cause fluid retention, and patients with kidney disorders should be carefully monitored.

If you are diabetic, you should be carefully monitored while taking HRT, as it may affect carbohydrate metabolism (peripheral insulin resistance and glucose tolerance).

If you have a uterine fibroid (a type of uterine tumor), it may increase in size due to the influence of estrogens. In this case, treatment should be discontinued.

If you suffer from the reactivation of endometriosis (a disease of the reproductive organs), it is recommended to discontinue treatment.

If you have a prolactinoma (a non-cancerous tumor that causes an increase in prolactin secretion), close medical supervision is necessary (including periodic measurement of prolactin levels).

If you develop chloasma (skin discoloration in patches with irregular contours, yellowish-brown in color, which appears mainly on the face) during HRT treatment, especially if you have a history of chloasma during pregnancy, you should avoid sun exposure or ultraviolet rays while taking HRT.

You should evaluate with your doctor the possible alternative treatments available for your specific situation and how long treatment should be continued. This should be reviewed periodically throughout treatment.

Hormone replacement therapy does not prevent memory loss. There is some evidence of greater memory loss in women who start using HRT after the age of 65. Ask your doctor for advice.

In women with hereditary angioedema (a type of allergic swelling that usually appears on the face), exogenous estrogens such as those contained in Progynova may induce or worsen symptoms.

Progynova is not a contraceptive and should not be used as such; it also does not restore fertility.

To avoid pregnancy, non-hormonal contraceptive measures should be used when necessary (with the exception of rhythm and temperature methods). If there are indications of pregnancy, you should stop taking the pills until pregnancy has been ruled out (see section "Pregnancy and Breastfeeding").

Laboratory tests

If you need a blood test, inform your doctor or the laboratory staff that you are taking Progynova, as it may affect the results of certain laboratory tests or analyses.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant or plan to become pregnant, consult your doctor before taking Progynova.

3. How to take Progynova

Follow the administration instructions for this medication exactly as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Your doctor should always consider the administration of the lowest dose and the shortest treatment duration. If you think the effect of Progynova is too strong or too weak, tell your doctor or pharmacist.

Remember to take your medication.

• Adult women, including the elderly.

If you are hysterectomized (have had your uterus partially or totally removed), you can start treatment at any time.

If you have your uterus intact and still have menstrual cycles, treatment should begin within 5 days of the start of menstruation, combining Progynova with a progestogen (see "Combined regimen" below).

If you do not have menstrual periods, have very infrequent periods, or are postmenopausal, you can start treatment combining Progynova with a progestogen (see "Combined regimen" below) at any time, as long as a possible pregnancy has been ruled out.

Dosage

Unless your doctor tells you otherwise, treatment is started by taking two Progynova 1 mg tablets daily without chewing, after a meal. After some time, your doctor may reduce the dose to one 1 mg tablet daily.

After 6 months of treatment, it is recommended to interrupt the medication to check if the symptoms still persist.

Administration

After each 20-day cycle of treatment, you can take a break from taking the coated tablets, usually for a week or less (cyclic HRT), or you can continue taking the coated tablets without interruption (continuous HRT). In the latter case, you start a new pack directly after finishing the previous one.

Combined regimen:

If you have your uterus intact, it is recommended to use a suitable progestogen concurrently for 10-14 days every 4 weeks (sequential combined HRT) or with each estrogen-coated tablet (continuous combined HRT).

Your doctor should make adequate provision to facilitate and ensure appropriate compliance with the recommended combined regimen.

The tablets should be taken without chewing, with some liquid.

The time of day you take the tablet is irrelevant, but once you have chosen a specific time, you should maintain it every day.

It is not recommended to add a progestogen in hysterectomized women, unless there is a prior diagnosis of endometriosis.

Switching from other HRT treatments (cyclic, sequential, or continuous combined regimen):

If you switch from other HRT treatments, you should finish your treatment cycle before starting treatment with Progynova.

If you think the effect of Progynova is too strong or too weak, tell your doctor or pharmacist.

Children and adolescents

Progynova is not indicated for use in children and adolescents.

Special populations

Elderly patients

There are no data suggesting a need for dose adjustment in elderly patients.

Patients with hepatic impairment

Progynova has not been specifically studied in patients with hepatic impairment. Progynova is contraindicated in women with severe hepatic disease (see section "Do not take Progynova").

Patients with renal impairment

Progynova has not been specifically studied in patients with renal impairment.

If you take more Progynova than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

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

If you forget to take Progynova

Do not take a double dose to make up for forgotten doses.

If you have forgotten to take a tablet and less than 24 hours have passed, take the tablet as soon as possible and take the next tablet at your usual time. If treatment is suspended for a longer period, irregular bleeding may occur.

If you stop treatment with Progynova

Your doctor will indicate the duration of your treatment. Do not stop treatment before, as it may not have the desired effect.

If you need surgery

If you are going to undergo surgery, inform the surgeon that you are taking Progynova. You may need to discontinue treatment with Progynova for 4 to 6 weeks before surgery to reduce the risk of blood clots (see also section 2 "Blood clots in a vein"). Ask your doctor when you can resume treatment with Progynova.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone gets them.

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

• 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)
• coronary heart disease
• stroke
• possible memory loss if HRT is started after the age of 65.

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

In addition to the side effects listed in the "Warnings and precautions" section, the following possible side effects are reported in users of different oral HRT preparations, according to the part of the body they affect and their frequency of occurrence:

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

Weight gain, weight loss

Headache

Abdominal pain, nausea

Rash, itching

Vaginal bleeding, including spotting

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

Hypersensitivity reaction (allergic)

Depressive mood

Dizziness

Visual disturbances

Palpitations

Dyspepsia (difficult digestion)

Erythema nodosum (inflammation of the skin with the appearance of nodules, usually on the legs)

Urticaria

Breast pain, breast tenderness

Edema (fluid retention)

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

Anxiety, increased libido (sexual desire), decreased libido

Migraine

Intolerance to contact lenses

Bloating, vomiting

Hirsutism (excessive hair growth), acne

Muscle cramps

Dysmenorrhea (painful menstruation), vaginal discharge, premenstrual syndrome, breast enlargement

Fatigue

In women with hereditary angioedema (allergic swelling or edema that usually appears on the face), exogenous estrogens like those in Progynova may induce or worsen symptoms (see "Warnings and precautions").

The following side effects have been reported in relation to other medications used in HRT:

• Gallbladder disease.
• Subcutaneous and skin disorders:
• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma) (skin spots),
• rash with redness in a target shape or blisters (erythema multiforme) (a type of skin inflammation),
• red, painful nodules on the skin (erythema nodosum) (a type of skin inflammation with the appearance of nodules on the legs),
• vascular purpura (red spots on the skin).
• Possible dementia in women over 65 years old (see "Warnings and precautions").

Reporting side effects:

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medication Surveillance System for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Progynova

Keep this medication out of sight and reach of children.

No special storage conditions are required.

Do not use Progynova after the expiration date stated on the packaging after EXP. The expiration date is the last day of the month indicated.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and any unused medication in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package contents and additional information

Composition of Progynova

• The active ingredient is estradiol valerate.

Each coated tablet contains 1 mg of estradiol valerate.

• The other ingredients are: lactose monohydrate, cornstarch, povidone 25,000, talc, magnesium stearate, sucrose, povidone 700,000, macrogol 6,000, calcium carbonate, montan wax, glycerol 85% (E-422), titanium dioxide (E-171), yellow iron oxide (E-172).

Appearance of the product and package contents

Progynova is presented in a box containing a blister pack with 20 coated tablets of beige color.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bayer Hispania, S.L.

Av. Baix Llobregat, 3 - 5

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer

Bayer Weimar GmbH und Co. KG

Döbereinerstrasse 20

99427 Weimar

Germany

or

Bayer AG

Müllerstrasse 178

13353 Berlin

Germany

Date of last revision of this leaflet:January 2024

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