Prospecto: Information for the User

Progyluton Coated Tablets

Valerato de estradiol / norgestrel

1.What Progyluton is and for what it is used

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

3.How to take Progyluton

1. Possible adverse effects
2. Storage of Progyluton
3. Contents of the package and additional information

Progyluton is a hormonal medication.

This medication is indicated for hormonal replacement therapy (HRT) for the treatment of symptoms caused by estrogen deficiency (female sex hormones) due to natural menopause (the period of time in which reproductive function and menstruation cease in a woman) or surgically induced menopause (castration).

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

Progyluton is not a contraceptive, nor does it restore fertility.

Follow carefully all the instructions given by your doctor.

Read the following information before using Progyluton.

Medical history and regular check-ups

The use of THS involves risks that must 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 resuming) THS, 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 started on treatment with Progyluton, you must visit your doctor for regular check-ups (at least once a year). In these controls, consult with your doctor about the benefits and risks of continuing with Progyluton.

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

Do not take Progyluton

if any of the following cases affect you. If you are unsure about any of the following points, consult your doctor before taking Progyluton.

• If you have or have had breast cancer or if you suspect you may have it.
• If you have acancer that depends on the action of estrogens, such as endometrial cancer, or if you suspect you may have it.
• If you have known or suspected premalignant lesions influenced by sex hormones or hormone-dependent tumors.
• If you are pregnant or suspect you may be, or if you are breastfeeding.

• If you haveabnormal vaginal bleeding.

• If you haveunexcessive thickening of the inner wall of the uterus(endometrial hyperplasia)that is not being treated.
• If you have a history of herpes during pregnancy.

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

• If you haveablood clotting disorder(such as protein C deficiency, protein S deficiency, or antithrombin deficiency).

• If you have or have had recently had a thrombosis of an artery (e.g.:angina pectoris, myocardial infarction, stroke).

• If you have or have had aliver disease,and your liver function tests have not returned to normal.

• If you havearare blood disorder called “porphyria”that is inherited.
• If you have sickle cell anemia (a blood disorder).
• If you areallergic to estradiol valerate, norgestrelor to any of the other components of this medication (including those in section 6).

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take Progyluton.

Visit your doctor regularly and, at least, once a year. Discuss with your doctor in each visit about 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. If the risk is too high, your doctor will not prescribe THS.

For the treatment of menopausal symptoms, THS should only be initiated when symptoms affect the quality of life of the woman. In all cases, a careful assessment of the risks and benefits should be made annually, and THS should only be continued while the benefits outweigh the risks. The administration of the lowest possible dose and the shortest duration of treatment should always be considered.

When taking special precautions with Progyluton

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 Progyluton. If so, you should visit your doctor more frequently for check-ups.

• Any type of gynecological disorder, such as frequent or persistent irregular uterine bleeding, fibroids (a type of uterine tumor), endometriosis (the appearance of tissue that covers the uterus outside its usual location), or untreatedendometrial hyperplasia.

• 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 alteration due to the risk of developing pancreatitis (inflammation of the pancreas).

• High blood pressure.

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

• Diabetes.

• Stones in the gallbladder.

• Migraines or severe headaches.

• A disease of the immune system that affects many organs of the body(systemic lupus erythematosus, SLE).
• Multiple sclerosis (a disease of the nervous system).

• Epilepsy.

• Asthma.

• Pruritus (itching).

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

• Corpus minor (a disease of the nervous system).
• Fluid retention due to cardiac or renal problems.
• Hereditary and acquired angioedema.

Stop taking Progyluton and go to your doctor immediately

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

• any of the disorders mentioned in the section “Do not take Progyluton”,
• yellowing of the skin or the 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, which suggests angioedema,
• a significant increase in blood pressure (the symptoms may be headache, fatigue, dizziness),
• migraine-like 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: Progyluton is not an anticonceptive. If you have 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.

Be especially careful not to exceed the recommended doses.

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

THS and cancer

Endometrial hyperplasia and endometrial cancer

THS with estrogen alone increases the risk of endometrial hyperplasia and endometrial cancer.

The progestogen in Progyluton protects against this increased risk.

In women with an intact uterus who are not using THS, a mean of 5 out of every 1,000 women, aged 50-65 years, will be diagnosed with endometrial cancer. In women with an intact uterus who use THS with estrogen alone, a mean of 10 to 60 out of every 1,000 women, aged 50-65 years, 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 bleeding ofdeprivation) while taking Progyluton. However, if you have irregular bleeding or spotting in addition to your menstrual period, which:

• continues for more than 6 months;
• starts after being on Progyluton for more than 6 months;
• continues after stopping treatment with Progyluton;

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 estrogen alone increases the risk of breast cancer.The additional risk depends on the duration of 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 you have used HRT for more than 5 years.

Your doctor will advise you on how to detect abnormalities in your breasts and will perform regular check-ups throughout treatment.

Comparison

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

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

•moles on the skin

•changes in the nipple

•any lump that you can see or feel

Additionally, it is recommended that you join the breast cancer screening programs when offered. For breast cancer screening, it is essential to inform the nurse/healthcare professional who performs the radiography that you are a user of HRT, as these medications can increase the density of the breasts, which can affect the result of the mammography. 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 estrogen 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, approximately 2 cases of ovarian cancer per 2,000 women have been observed in a 5-year period. In women on HRT for 5 years, approximately 3 cases per 2,000 patients have been observed (i.e. approximately 1 additional case).

Effects of THS on the heart and circulation

Thrombosis in a vein

The risk of developingthrombosis in the veinsis approximately 1.3 to 3 times higher in HRT users compared to non-users, especiallyduring the first year of use.

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

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

• You cannot walk for a prolonged period due to a major surgery, injury, or illness (see also section 3, If you need to undergo a surgical procedure)
• 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
• One of your close relatives has had a blood clot in the leg, lung, or any other organ
• You have systemic lupus erythematosus (SLE)
• You have cancer.

For the symptoms of a blood clot, see “Stop taking Progyluton and go to your doctor immediately”.

Comparison

In women aged 50 who are not using HRT, a mean of 4 to 7 out 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 for more than 5 years, there will be 9 to 12 cases per 1,000 users (i.e. 5 additional cases).

Arterial thromboembolism

In large clinical trials with estrogen conjugates and medroxyprogesterone acetate (MPA) combinations, a possible increase in cardiovascular pathology and an increase in the risk of stroke were observed.The extent to which these findings can be extended to other HRT compounds containing different estrogens and progestogens, such as Progyluton, is unknown.

Coronary heart disease (heart attack)

HRT does not prevent heart attacks.HRT should not be used to prevent cardiovascular diseases.

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 developing 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 aged 50 who are not using HRT, a mean of 8 out 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 disorders

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

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

If you develop a melasma (skin discoloration in patches of irregular contours of dark brownish yellow color, which appears mainly on the face) during HRT treatment, especially in women with a history of melasma during pregnancy, you should avoid exposure to the sun or ultraviolet rays while on treatment.

Inform your doctor if you experience any alteration in kidney or heart function. Estrogens can cause fluid retention, and patients with kidney function disorders should be closely monitored.

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

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

If you experience the reactivation of endometriosis (a disorder of the reproductive organs tissue), you should suspend treatment.

Progyluton is not an anticonceptive and does not restore fertility.

To prevent pregnancy, additional contraceptive methods will be used when necessary, using non-hormonal methods (except for the rhythm and temperature methods). If there are indications to suspect the presence of a pregnancy, treatment should be interrupted until it has been confirmed (see section “Pregnancy and lactation”).

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

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

Laboratory tests

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

Children and adolescents

Progyluton is not indicated for use in children and adolescents.

Use of Progyluton with other medications

Inform your doctor or pharmacist if you are taking, have taken recentlyor may need to takeany other medication, including those acquired without a prescription,herbal remediesor other natural products.

Certain medications may interact with the effect of Progyluton. This may cause irregular bleeding. In these cases, it may be necessary to change the dose or discontinue treatment with one of the medications. This applies to the following medications:

• Antiepileptic medications(e.g. barbiturates, phenytoin, primidone, carbamazepine, and possibly oxcarbazepine, topiramate, and felbamate).

• Tuberculosis medications(e.g. rifampicin and rifabutin)

• Medications forthe treatment of HIV and hepatitis C(the so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors) (e.g. nevirapine, efavirenz, ritonavir, nelfinavir)

• Herbal remedies containingSt. John's Wort(Hypericum perforatum), used for depression. The effect of these preparations persists for up to two weeks after they have been discontinued.

• Antifungal medications(e.g. griseofulvin, fluconazole, itraconazole, ketoconazole, and voriconazole)

• Antibacterial medications(e.g. 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 for epilepsy (lamotrigine), as it may increase the frequency ofseizures.
• Medications for hepatitis C (VHC) (e.g., the combination regimen for VHC 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 ethinyl estradiol. Progyluton contains estradiol instead of ethinyl estradiol. It is unknown whether an increase in ALT levels may occur when Progyluton is used with this combination regimen for VHC.

There are substances (e.g. paracetamol) that may increase the amount of estradiol in the blood and, therefore, may increase its effect.

In individual cases, the requirements for oral antidiabetic medications or insulin may vary due to the effects on glucose tolerance.

Be aware that these instructions may also apply if the use of other medications occurs before or after the use of Progyluton.

Inform your doctor or pharmacist if you are taking, have taken recentlyor may need to take any other medication. Your doctor will advise you accordingly.

Pregnancy and lactation

If you are pregnant, or in the lactation period, think you may be pregnant, or intend to become pregnantconsult your doctor or pharmacist before using any medication.

The use of Progyluton is indicated only in postmenopausal women. Do not use Progyluton if you are pregnant or want to become pregnant.If pregnancy occurs during treatment with Progyluton, it should be discontinued immediately.

Do not use Progyluton if you are breastfeeding. Small amounts of sex hormones may pass into breast milk.

Driving and operating machinery

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

Progyluton contains lactose and saccharose

If your doctor has told you that you have a intolerance to certain sugars, consult with him before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist.In case of doubt, consult your doctor or pharmacist.

Remember to take your medication.

If you still have menstrual cycles, treatment should start on the fifth day of the cycle (first day of menstrual bleeding = first day of the cycle).

If you have amenorrhea (lack of menstruation) or infrequent periods or are postmenopausal, you can start treatment at any time, once a pregnancy has been previously ruled out.

Dosage

Take a white tablet once a day for the first 11 days, followed by a light brown tablet once a day for 10 days. After 21 days of treatment, there will be a 7-day interval without taking tablets.

Administration

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

Each package allows for 21 days of treatment. After the 7-day interval without medication, you should start a new package of Progyluton on the same day of the week that you started with the previous one.

To do this, simply extract the first tablet from each package of Progyluton from the pink box "Start" and continue with a daily tablet following the arrow direction.

It is indifferent what time of day you take the tablet, but once you have selected a specific time, you should maintain it every day.

During the 7-day interval without taking tablets, bleeding usually appears a few days after taking the last tablet.

For both the start and continuation of menopausal symptoms, the minimum effective dose should be used for the shortest possible treatment time.

If you estimate that Progyluton's action is too strong or too weak, inform your doctor or pharmacist.

Special populations

Patients with liver insufficiency

Progyluton has not been specifically studied in patients with liver insufficiency. Progyluton is contraindicated in women with severe liver diseases (see section "Do not take Progyluton").

Patients with renal insufficiency

Progyluton has not been specifically studied in patients with renal insufficiency.

Older patients

There are no data suggesting a need for dosage adjustment in older patients.

If you take more Progyluton than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the package and leaflet to the healthcare professional.

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

If you forgot to take Progyluton

Do not take a double dose to compensate for the missed 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 more than 24 hours have passed, leave the forgotten tablet in the blister. Continue taking the remaining tablets at your usual time every day. If treatment is suspended for a longer period, irregular bleeding may appear.

If you interrupt treatment with Progyluton

Your doctor will indicate the duration of your treatment with Progyluton. Do not suspend treatment prematurely, as it may not have the desired effect.

If you need surgery

If you are about to undergo surgery, inform the surgeon that you are taking Progyluton. You may need to stop taking Progyluton 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 Progyluton.

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

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

The following diseases occur more frequently in women taking THS compared to women who are 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)

•coronary 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.

In addition to the side effects listed in the "Warnings and Precautions" section, the following possible side effects, according to the part of the body affected and their frequency of occurrence, have been reported in users of different oral preparations of THS:

• Frequent side effects:may affect up to 1 in 10 people

Weight gain, weight loss

Headache

Abdominal pain, nausea

Skin rash, pruritus (itching)

Vaginal bleeding including spotting

• Rare side effects:may affect up to 1 in 100 people

Reactions of hypersensitivity (allergic)

Depressive mood

Dizziness

Visual disturbances

Palpitations

Indigestion (difficult digestion)

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

Urticaria

Mastalgia, 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

Swelling, vomiting

Hirsutism (excessive hair growth), acne

Muscle cramps

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

Fatigue

In women with hereditary angioedema (allergic swelling or edema that usually appears on the face), exogenous estrogens such as those contained in Progyluton may induce or worsen symptoms (see "Warnings and Precautions").

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

• Estrogen-dependent neoplasms, benign or malignant, e.g. endometrial cancer.
• Venous thromboembolism, e.g. deep vein thrombosis in the legs or pelvis and pulmonary embolism, exacerbation of varicose veins, hypertension (see "Do not take Progyluton" and "Warnings and Precautions").
• Myocardial infarction.
• Stroke.
• Subcutaneous and skin alterations:
• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma) (skin spots),
• skin rash with redness in the form of a target or sores (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),
• contact dermatitis,
• skin pigmentation changes,
• generalized itching and
• exanthema (skin rash).
• Biliary tract disease.
• Probable dementia in women over 65 years old (see "Warnings and Precautions").

Reporting of 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.

No special storage conditions are required.

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.

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. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Progyluton

-The active principles are: valerato de estradiol and norgestrel.

Each white coated tablet contains 2 mg of valerato de estradiol.

Each light brown coated tablet contains 2 mg of valerato de estradiol and 0.5 mg of norgestrel.

-The other components are:

White coated tablet: lactose monohydrate, cornstarch, povidone 25000, talc, magnesium stearate, sucrose, povidone 700000, macrogol 6000, calcium carbonate, montan wax.

Light brown coated tablet: lactose monohydrate, cornstarch, povidone 25000, talc, magnesium stearate, sucrose, povidone 700000, macrogol 6000, calcium carbonate, montan wax, glycerol 85% (E-422), titanium dioxide (E-171), yellow iron oxide (E-172), red iron oxide (E-172).

Appearance of the product and content of the packaging

Progyluton is presented in a box containing a blister pack with 21 coated tablets (11 white and 10 light brown).

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Bayer Hispania, S.L.

Av. Baix Llobregat, 3 - 5

08970 Sant Joan Despí (Barcelona)

Spain

Responsible for manufacturing

Bayer Weimar GmbH und Co.KG

Döbereiner Str. 20, 99427 Weimar

Germany

or

Bayer AG

Müllerstrasse 178

13353 Berlin

Germany

Last review date of this leaflet: January 2024

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