Progyluton coated tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Progyluton coated tablets

Estradiol valerate / norgestrel

Package leaflet contents

1. What Progyluton is and what it is used for
2. What you need to know before taking Progyluton
3. How to take Progyluton
   1. Possible side effects
   2. How to store Progyluton
   3. Contents of the pack and other information

1. What Progyluton is and what it is used for

Progyluton is a hormonal medicine.

This medicine is indicated for hormone replacement therapy (HRT) to treat symptoms caused by estrogen deficiency (female sex hormones) due to natural menopause (the period when reproductive function and menstruation cease in a woman) or surgically induced menopause (castration).

Progyluton must not be used to prevent heart disease or to enhance intellectual capacity.

Progyluton is not a contraceptive and does not restore fertility.

2. What you need to know before starting Progyluton

Carefully follow all instructions given by your doctor.

Read the following information before using Progyluton.

Medical history and regular check-ups

Hormone replacement therapy (HRT) carries risks that must be considered when deciding whether to start or continue treatment.

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 HRT may differ. 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 treatment with Progyluton has started, you should visit your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Progyluton.

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

Do not take Progyluton

if any of the following apply to 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 suspect you may have it.

• If you have a cancer dependent on estrogen action, such as cancer of the inner lining of the uterus (endometrium), 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 pregnant, or if you are breastfeeding.

• If you have abnormal vaginal bleeding.

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

• If you have a history of herpes gestationis (herpes during pregnancy).

• If you have or have had formation of a blood clot in a vein (thrombosis), e.g., in the legs (deep vein thrombosis) or in the 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 thrombosis in an artery (e.g.: angina pectoris, myocardial infarction, stroke).

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

• If you have a rare inherited blood disorder called "porphyria" passed from parents to children (hereditary).

• If you have sickle cell anemia (a blood disorder).

• If you are allergic to estradiol valerate, norgestrel, or any of the other components of this medicine (listed in section 6).

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

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 at each visit whether the treatment needs adjustment or continuation. Your doctor will assess whether you are at increased risk of thrombosis due to a combination of risk factors or a single high-risk factor. If multiple risk factors are present, the risk may be higher than simply adding two individual risks. If the risk is too high, your doctor will not prescribe HRT.

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

When to take special precautions with Progyluton

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

• Gynecological disorders such as frequent or persistent irregular uterine bleeding, fibroids (a type of uterine tumor), endometriosis (presence of uterine lining tissue outside its normal location), or history of endometrial hyperplasia (abnormal proliferation of cells lining the inside of the uterus).

• Increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”)

• Increased risk of developing an estrogen-dependent cancer (e.g., having a mother, sister, or grandmother who had breast cancer)

• Changes or abnormalities in the breasts.

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

• High blood pressure.

• Liver disorders, such as a benign liver tumor.

• Kidney disorders.

• Diabetes.

• Gallstones.

• Migraines or severe headaches.

• An autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE).

• Multiple sclerosis (a nervous system disease).

• Epilepsy.

• Asthma.

• Pruritus (itching).

• Otosclerosis (abnormal bone growth in the ear), a condition affecting the eardrum and ear.

• Chorea minor (a nervous system disorder).

• Fluid retention due to heart or kidney problems.

• Hereditary and acquired angioedema.

Stop taking Progyluton and see your doctor immediately

If you experience any of the following conditions while taking HRT:

• any of the conditions listed in the section “Do not take Progyluton”,
• 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 hives accompanied by difficulty breathing, suggesting angioedema,
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness),
• new-onset migraine-type headaches,
• if you become pregnant,
• if you notice signs of a blood clot, such as:
  • painful swelling and redness in the legs,
  • sudden chest pain,
  • difficulty breathing.

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

Note: Progyluton is not a contraceptive. If less than 12 months have passed 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. Seek advice from your doctor.

Take special care not to exceed the recommended doses.

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

HRT and cancer

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

Estrogen-only HRT increases the risk of excessive thickening of the inner lining of the uterus (endometrial hyperplasia) and cancer of the inner lining of the uterus (endometrial cancer).

The progestogen contained in Progyluton protects you from this increased risk.

In women with an intact uterus who do not use HRT, an average of 5 out of 1,000 women aged 50 to 65 will be diagnosed with endometrial cancer. In women with an intact uterus using estrogen-only HRT, an average of 10 to 60 out of 1,000 women aged 50 to 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 a monthly menstrual bleed (also called withdrawal bleeding) while taking Progyluton. However, if you experience irregular bleeding or spotting in addition to your menstrual period that:

• continues beyond the first 6 months;
• starts after having taken Progyluton for more than 6 months;
• continues after stopping treatment with Progyluton;

consult your doctor as soon as possible.

Breast cancer

Available data show that the use of combined estrogen-progestogen hormone replacement therapy (HRT) or estrogen-only HRT increases the risk of breast cancer. The additional risk depends on how long you use HRT. The additional risk becomes evident after 3 years of use. After stopping HRT, the additional risk decreases over time, but may persist for 10 years or more if HRT has been used for more than 5 years.

Your doctor will advise you on how to detect breast abnormalities and will perform periodic checks during treatment.

Comparison

In women aged 50 to 54 years not using HRT, an average of 13 to 17 out of 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 to 17 cases per 1,000 women users (i.e., 0 to 3 additional cases).

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

In women aged 50 to 59 years 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 women users (i.e., 7 additional 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 additional cases).

Check your breasts regularly. Consult your doctor if you notice any changes such as:

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

In addition, it is recommended that you participate in screening mammography programs when offered. For screening mammograms, it is important to inform the nurse/healthcare professional performing the X-ray that you are using HRT, as these medicines can increase breast density, which may affect the mammogram result. When breast density increases, the mammogram may not detect all lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of estrogen-only HRT or combined estrogen-progestogen HRT 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 to 54 years not on HRT, about 2 cases of ovarian cancer per 2,000 women are observed over a 5-year period. In women on HRT for 5 years, about 3 cases per 2,000 patients are observed (i.e., about 1 additional case).

Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)

The risk of developing blood clots in 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, it can cause chest pain, difficulty breathing, fainting, or even death.

Your risk of developing a blood clot in the veins increases with age and if any of the following apply to you. Inform your doctor if any of these situations affect you:

• You cannot walk for a prolonged period due to major surgery, injury, or illness (see also section 3, If you need to undergo surgery)
• You have severe overweight (BMI > 30 kg/m²)
• You have a blood clotting disorder requiring long-term treatment with a medication used to prevent blood clots
• A close relative has 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 Progyluton and see your doctor immediately”.

Comparison

In women in their fifties not taking HRT, an average of 4 to 7 out of 1,000 are expected to have a blood clot in a vein over a 5-year period.

In women in their fifties who have been taking estrogen-progestogen HRT 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 conjugated estrogens and medroxyprogesterone acetate (MPA), a possible increase in cardiovascular disease risk and an increased risk of stroke were observed. It is unknown whether these findings can be extended to other HRT formulations containing different estrogens and progestogens, such as Progyluton.

Coronary heart disease (heart attack)

HRT has not been shown to prevent heart attacks. HRT should not be used to prevent cardiovascular diseases.

Women over 60 years of age using estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT.

Stroke

The risk of 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 fifties not taking HRT, an average of 8 out of 1,000 are expected to have a stroke over a 5-year period. For women in their fifties taking HRT, 11 cases per 1,000 users will occur over a 5-year period (i.e., 3 additional cases).

Other disorders

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

If you have a prolactinoma (a non-cancerous tumor causing increased secretion of the hormone prolactin), close medical supervision is required (including periodic measurement of prolactin levels).

If you develop chloasma (irregularly bordered, dark yellowish-brown skin patches, mainly appearing on the face) during HRT treatment, especially if you have a history of chloasma during pregnancy, you should avoid exposure to sunlight or ultraviolet rays while on treatment.

Inform your doctor if you have impaired kidney or heart function. Estrogens may cause fluid retention, and therefore patients with impaired kidney function should be carefully monitored.

You should discuss with your doctor the possible alternative treatments available for your specific condition and how long treatment should last. This should be reviewed periodically throughout treatment.

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

If you experience reactivation of endometriosis (a disorder of reproductive organ tissue), you are advised to stop treatment.

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

To prevent pregnancy, non-hormonal contraceptive methods (except rhythm and temperature methods) should be used when necessary. If there are signs suggesting pregnancy, stop taking the tablets until pregnancy is ruled out (see section “Pregnancy and lactation”).

HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start using HRT after age 65. Seek advice from your doctor.

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

Laboratory tests

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

Children and adolescents

Progyluton is not indicated for use in children and adolescents.

Use of Progyluton with other medicines

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

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

• Antiepileptic medicines (e.g., barbiturates, phenytoin, primidone, carbamazepine, and possibly oxcarbazepine, topiramate, and felbamate).
• Medicines for the treatment of tuberculosis (e.g., rifampicin and rifabutin)
• Medicines for HIV and Hepatitis C virus infection (protease inhibitors and non-nucleoside reverse transcriptase inhibitors) (e.g., nevirapine, efavirenz, ritonavir, nelfinavir)
• Herbal preparations containing St. John's wort (Hypericum perforatum), used for depression. The effect of these preparations persists for up to two weeks after stopping them.
• Medicines for the treatment of fungal infections (e.g., griseofulvin, fluconazole, itraconazole, ketoconazole, and voriconazole)
• Medicines for the treatment of bacterial infections (e.g., clarithromycin and erythromycin)
• Medicines for the treatment of certain heart diseases, high blood pressure (such as verapamil and diltiazem)
• Grapefruit juice

HRT may affect the functioning of other medicines:

• An epilepsy medicine (lamotrigine), as it could increase the frequency of seizures.
• Medicines for hepatitis C virus (HCV) (e.g., HCV combination regimens ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir) may cause elevations in liver function blood tests (increase in liver enzyme ALT) in women using HRT containing ethinylestradiol. Progyluton contains estradiol instead of ethinylestradiol. It is unknown whether an increase in liver enzyme ALT can occur when Progyluton is used with this HCV combination regimen.

Some substances (e.g., paracetamol) may increase the amount of circulating estradiol in the blood and, therefore, its effect may be enhanced.

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

Note that these instructions may also apply if other medicines are taken before or after Progyluton.

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine. Your doctor will advise you accordingly.

Pregnancy and lactation

If you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using any medicine.

Progyluton is indicated only in postmenopausal women. Do not use Progyluton if you are pregnant or wish to become pregnant. If pregnancy occurs during treatment with Progyluton, treatment must be stopped immediately.

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

Driving and using machines

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

Progyluton contains lactose and sucrose

If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

3. How to take Progyluton

Follow exactly the instructions for use of this medicine provided by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.

Remember to take your medicine.

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

If you have amenorrhea (absence of menstruation) or very infrequent periods, or if you are postmenopausal, you may start treatment at any time, provided that pregnancy has previously been excluded.

Posology

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

Administration

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

Each pack provides treatment for 21 days. After the 7-day drug-free interval, you should start a new pack of Progyluton, on the same day of the week as you started the previous one.

To do this, simply always remove the first tablet from the pink-labeled "Start" cell of each Progyluton pack and continue taking one tablet daily, following the direction of the arrows.

It does not matter what time of day you take the tablet, but once you have chosen a specific time, you should maintain it every day.

During the 7-day tablet-free interval, bleeding usually occurs a few days after taking the last tablet.

For both the onset and continuation of menopausal symptoms, the lowest effective dose should always be used for the shortest possible treatment duration.

If you feel that the effect of Progyluton is too strong or too weak, inform your doctor or pharmacist.

Special populations

Patients with hepatic impairment

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

Patients with renal impairment

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

Elderly patients

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

If you take more Progyluton than you should

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

Overdose may cause nausea, vomiting, and irregular bleeding. Specific treatment is not required, but you should consult your doctor if you are concerned.

If you forget to take Progyluton

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

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 pack. Continue taking the remaining tablets at your usual time each day. If treatment is interrupted for a longer period, irregular bleeding may occur.

If you stop taking Progyluton

Your doctor will advise you on the duration of your treatment with Progyluton. Do not stop treatment prematurely, as it may not achieve the desired effect.

If you need surgery

If you are undergoing surgery, inform your 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 further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

The following conditions occur more frequently in women using HRT compared to women who do not take HRT:

• Breast cancer
• Abnormal growth or cancer of the inner lining of the womb (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 about these adverse effects, see section 2.

In addition to the adverse effects listed in the section “Warnings and precautions”, the following possible adverse effects, classified by the affected body system and frequency of occurrence, have been reported in users of various oral HRT preparations.

• Frequent adverse 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

• Uncommon adverse effects: may affect up to 1 in 100 people

Hypersensitivity reaction (allergic)
Depressed mood
Dizziness
Visual disturbances
Palpitations
Dyspepsia (indigestion)
Erythema nodosum (skin inflammation with appearance of nodules, usually on the legs)
Urticaria
Breast pain, breast tenderness
Edema (fluid retention)

• Rare adverse 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 (swelling or allergic-type edema usually affecting the face), exogenous estrogens such as those contained in Progyluton may induce or worsen symptoms (see section “Warnings and precautions”).

The following adverse effects have been reported with other HRT medicines:

• Estrogen-dependent benign or malignant neoplasms, e.g., endometrial cancer.
• Venous thromboembolism, e.g., deep vein thrombosis in legs or pelvis and pulmonary embolism, worsening of varicose veins, hypertension (see section “Do not take Progyluton” and “Warnings and precautions”).
• Myocardial infarction.
• Stroke.
• Subcutaneous and skin disorders:
  • Skin discoloration, especially on the face or neck, known as “chloasma” (melasma) (skin patches),
  • Skin rash with red, target-like lesions or sores (erythema multiforme) (a type of skin inflammation),
  • Painful red nodules on the skin (erythema nodosum) (a type of skin inflammation with nodules appearing on the legs),
  • Vascular purpura (red skin spots),
  • Contact dermatitis,
  • Pigmentation disorders,
  • Generalized itching, and
  • Exanthema (skin rash).
• Gallbladder disease.
• Possible dementia in women over 65 years of age (see section “Warnings and precautions”).

Reporting of adverse effects:

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Progyluton

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

No special storage conditions are required.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Unused medicines and their containers should be handed in at a SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of unused medicines and their packaging. This will help protect the environment.

6. Package contents and additional information

Composition of Progyluton

• The active substances are: estradiol valerate and norgestrel.

Each white coated tablet contains 2 mg of estradiol valerate.

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

• The other components are:

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

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

Presentation of the product and contents of the package

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

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

Döbereiner Str. 20, 99427 Weimar

Germany

or

Bayer AG

Müllerstrasse 178

13353 Berlin

Germany

Date of the most recent review of this leaflet: September 2025

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