Prospecto: information for the user

Progynova 1 mg coated tablets

Valerate of estradiol

1.What Progynova is and for what it is used

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

3.How to take Progynova

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

Progynova is a hormonal medication.

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

treatment of menopausal symptoms (the time period in which reproductive function and menstruation cease in a woman), natural or surgically induced (castration), e.g. hot flashes, nocturnal sweating, urogenital disorders (atrophic vulvovaginitis).

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

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

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

Follow carefully all the instructions given by your doctor.

Read the following information before using Progynova.

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

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

Do not take Progynova

if any of the following cases affect 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 suspect you may be pregnant or if you are breastfeeding.
• If you have or have hadbreast canceror if you suspect you may have it.
• If you haveknown or suspected premalignant lesionsinfluenced by sex hormones.
• If you haveacancer that depends on the action of estrogens,such as endometrial canceror if you suspect you may have it.

• If you haveabnormal vaginal bleeding.

• If you haveexcessive thickening of the uterine lining (endometrial hyperplasia) that is not being treated.

• If you have or have hada blood clot in a vein(thrombosis),for example, in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).

• If you haveany alteration that affects blood coagulation(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 (arterial thrombosis), (e.g.angina pectoris, myocardial infarction, stroke).

• If you have or have had anyliver disease, and liver function tests have not returned to normal.
• Ifyou have a rare blood disorder called “porphyria”that is inherited.
• If you have sickle cell anemia (blood disorder).

• If you areallergictoestradiol valerateor 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 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 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, and THS should only be continued while the benefits outweigh the risks. The administration of the lowest dose and the shortest duration of treatment should always be considered.

When taking special precautions with Progynova

Inform 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 type, such as irregular, frequent, or persistent uterine bleeding, fibroids (a type of uterine tumor), endometriosis (the appearance of tissue that covers the uterus outside its usual location)orunusual endometrial 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 some fats (triglycerides) in the blood or family history of this alteration 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.
• Renal disorders.

• Diabetes.

• Galstones in the gallbladder.

• Migraines or severe headaches.

• Systemic lupus erythematosus (LES), an autoimmune disease that affects many organs of the body.

• Epilepsy.

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

• 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).

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

Be careful not to exceed the recommended doses.

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

Stop taking Progynova and see 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 Progynova”,
• 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, which suggests angioedema,
• A significant increase in blood pressure (symptoms may include headache, fatigue, dizziness),
• Migraine-like headaches that occur for the first time,
• If you become pregnant,
• If you notice signs of a blood clot, such as,
• • Swollen, painful, and red legs,
  • Sudden chest pain,
  • Difficulty breathing.

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

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

THS and cancer

Endometrial hyperplasia and endometrial cancer

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

The use of a progestogen in addition to estrogen for at least 12 days per cycle of 28 days protects against this increased risk. If you still have a uterus, your doctor will prescribe another hormone, a progestogen, to reduce the risk of endometrial cancer.

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

In women with an intact uterus who do not use THS, a mean of 5per 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, between 10 and 60 per 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 withdrawal) while taking Progynova. However, if you have unexpected bleeding or spotting in addition to your menstrual period, which:

• Continues for more than 6 months;
• Starts after being on Progynova for more than 6 months;
• Continues after stopping treatment with Progynova;

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 during 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 years who are not using HRT, a mean of 13-17 per 1,000 will be diagnosed with breast cancer in a 5-year period.

In women aged 50 years who initiate HRT with estrogen alone for 5 years, there will be 16-17 cases per 1,000 users (i.e., 0-3 additional cases).

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

In women aged 50-59 years 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 years 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 years 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:

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

Additionally, it is recommended that you join 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 breast density, which can affect the results of the mammography. When 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 years who are not using HRT, approximately 2 cases of ovarian cancer per 2,000 women will be observed in a 5-year period. In women in treatment with HRT for 5 years, approximately 3 cases per 2,000 patients (i.e., approximately 1 additional case) will be observed.

Effects of THS on the heart and circulation

Thrombosis in a vein

The risk of developing thrombosis 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.

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 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 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 to prevent blood clots
• One of your close relativeshas had a blood clot in the leg, lung, or any other organ
• You have systemic lupus erythematosus (LES)
• You have cancer.

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

Comparison

In women aged 50-54 years who are not using HRT, a mean of 4-7 per 1,000 will have a blood clot in a vein in a 5-year period.

In women aged 50-54 years who have been taking HRT with estrogen-progestogen for 5 years, there will be 9-12 cases per 1,000 users (i.e., 5 additional cases).

In women aged 50-54 years who do not have a uterus and have been taking HRT with estrogen alone for 5 years, there will be 5-8 cases per 1,000 users (i.e., 1 additional case).

Blood clots can also occur in the arteries of the heart (myocardial infarction, angina pectoris), in the cerebral arteries (stroke), or in the eyes (loss of vision or double vision).

Coronary heart 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 taking any HRT.

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

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 50-54 years who are not using HRT, a mean of 8 per 1,000 will have a stroke in a 5-year period. In women aged 50-54 years who are taking HRT, there will be 11 cases per 1,000 users in a 5-year period (i.e., 3 additional cases).

Hepatic tumors

In rare cases, liver tumors have been observed after the use of hormone substances such as those contained in Progynova.

Other diseases

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

If you are diabetic, you should be closely controlled while taking HRT, as it can affect carbohydrate metabolism (peripheral resistance to insulin 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 that case, treatment should be suspended.

If you experience the reactivation of endometriosis(a pathology of the reproductive organs), it is recommended to suspend treatment.

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 with irregular borders of dark brown-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 taking treatment.

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

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

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

Progynovais not a contraceptive 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 pregnancy, treatment should be interrupted until it has been confirmed (see section “Pregnancy and Lactation”).

Laboratory tests

If you need a blood test,inform your doctoror the laboratory staffthat you are takingProgynova,as it may alter the results of certain tests or laboratory analyses.

Pregnancy and lactation

If you are pregnant or breastfeeding, or if you suspect you may be pregnant or intend to become pregnant,consult your doctor or pharmacist before using this medication.

Progynovais only indicated for postmenopausal women. Do not use Progynova if you are pregnant or want to become pregnant..If pregnancy occurs during treatment with Progynova, treatment should be stopped immediately.

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

Use of Progynova with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications,herbal remediesor other natural products.

Some medications may interfere with the effect of Progynova. 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)

- HIV and hepatitis C virus infection medications (the so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as nevirapine, efavirenz, ritonavir, nelfinavir)

- Herbal remedies containingSt. John's Wort(Hypericum perforatum). The effect of these preparations remains for up to two weeks after they have been discontinued.

- Fungal infection medications (e.g.griseofulvin, fluconazole, itraconazole, ketoconazole, and voriconazole)

- Bacterial infection medications (e.g.clarithromycin and erythromycin)

- Heart disease medications, high blood pressure (e.g.verapamil, diltiazem)

- Orange juice

HRT may affect the functioning of other medications:

- A medication for epilepsy (lamotrigine), as it may increase the frequency of seizures.

- Medications for hepatitis C virus (HCV) (e.g., combination regimen for HCV or ombitasvir/paritaprevir/ritonavir with or without dasabuvir or glecaprevir/pibrentasvir) may cause elevated liver enzyme levels (ALT) in women using HRT with ethinylestradiol. Progynova contains estradiol instead of ethinylestradiol. It is unknown whether an increase in ALT levels may occur when Progynova is used with this combination regimen for HCV.

- Some substances (e.g., paracetamol) 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 other medications are taken before or after taking Progynova.

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

Driving and operating machinery

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

Progynova contains lactose and sucrose

If your doctor has indicated 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 again.

Your doctor should always consider the administration of the lowest dose and the shortest duration of treatment.If you estimate that the action of Progynova is too strong or too weak, inform your doctor or pharmacist.

Remember to take your medication.

• Adult women, including those of advanced age.

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

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

If you do not have periods, your periods are very infrequent, or you are in the postmenopausal period, treatment can be started by combining Progynova with a progestogen (see "Combined regimen" below) at any time, provided a possible pregnancy has been ruled out.

Dosage

Unless your doctor tells you otherwise, treatment starts by taking two Progynova 1 mg tablets daily, without chewing, after a meal. After a certain 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 discomforts still persist.

Administration

After each 20-day treatment cycle, a pause in the intake of the coated tablets can be made, usually of one week or less (cyclic THS), or the intake of coated tablets can continue without interruption (continuous THS). In the latter case, a new package is started directly at the end of the previous one.

Combined regimen:

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

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

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

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.

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

Change from other THS treatments (cyclic, continuous sequential, or continuous combined):

If you change from other THS treatments, you should complete your treatment cycle before starting treatment with Progynova.

If you estimate that the action of Progynova is too strong or too weak, inform your doctor or pharmacist.

Children and adolescents

Progynova is not indicated for use in children and adolescents.

Special populations

Older patients

No data suggest a need for dosage adjustment in older patients.

Patients with liver insufficiency

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

Patients with renal insufficiency

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

If you take more Progynova 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.

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 Progynova

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 treatment is suspended for a longer period, irregular bleeding may appear.

If you interrupt treatment with Progynova

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

If you need surgical intervention

If you are about to undergo surgery, inform the surgeon that you are taking Progynova. You may need to interrupt 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 doubts 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 lining 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)

• Very 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 syndrome, breast enlargement

Fatigue

In women with hereditary angioedema (allergic type of swelling or edema that usually appears on the face), exogenous estrogens such as those contained 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 THS:

• Biliary tract disease.
• Subcutaneous and skin alterations:
• skin discoloration, especially on the face or neck, known as "pregnancy spots" (melasma) (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).
• 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 of 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 Progynova 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 the packaging and unused medications 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 Progynova

-The active ingredient is valerianate of estradiol.

Each coated tablet contains 1 mg of valerianate of estradiol.

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

Appearance of the product and contents of the packaging

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

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

Döbereinerstrasse 20

99427 Weimar

Germany

or

Bayer AG

Müllerstrasse 178

13353 Berlin

Germany

Last review date of this leaflet:January 2024

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