Label: Information for the User

Vagirux 10 micrograms Vaginal Tablets

estradiol

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
  If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you alone, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Contents of the package and additional information

Vagirux contains estradiol.

• Estradiol is a female sex hormone.
• It belongs to the group of hormones called estrogens.
• It is exactly the same as estradiol produced in the ovaries of women.

Vagirux belongs to the group of medications called Vaginal Hormone Replacement Therapy (VHRT).

Vagirux is used torelieve vaginal menopausal symptoms such as dryness or irritation. In medical terms, this is known as "vaginal atrophy". It is caused by a decrease in estrogen levels in the body. This occurs naturally with menopause.

Vagirux actsby substituting the estrogen that is normally produced in the ovaries of women. It is inserted into the interior of your vagina, so that the hormone is released in the place where it is needed.This may relieve vaginal discomfort.

Medical History and Regular Check-ups

The use of THS involves risks that should be considered when deciding whether to start using it or continue treatment.

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

Before starting (or resuming) the use of THS, your doctor will ask about your family medical history. Your doctor may decide to perform a physical examination. This may include an examination of your breasts and/or internal examination, if necessary.

Once you have started using Vagirux, you should consult your doctor for check-ups at least once a year. In these check-ups, consult your doctor about the benefits and risks of continuing to use Vagirux.

Attend regular breast examinations as indicated by your doctor.

Do not use Vagirux

If you are in any of the following situations. If you are unsure about any of the following conditions, consult your doctor before using Vagirux.

Do not use Vagirux:

• if you have or have had breast cancer, or if you suspect you may have it
• if you have or have had cancer dependent on estrogen such as endometrial cancer or if you suspect you may have it
• if you have abnormal vaginal bleeding
• if you have an uncontrolled growth of cells that cover the uterus (endometrial hyperplasia)
• if you have or have had blood clots in a vein (deep vein thrombosis) or in the lungs (pulmonary embolism)
• if you have a blood clotting disorder (such as protein C deficiency, protein S deficiency, or antithrombin deficiency)
• if you have or have had a disease caused by blood clots in the arteries such as a heart attack, stroke, or angina pectoris
• if you have or have had liver disease and your liver function tests have not returned to normal
• if you have a rare blood disorder called "porphyria" that is inherited
• if you are allergic (hypersensitive) to estradiol or to any of the other components of Vagirux (including those listed in section 6 "Contents of the package and additional information")

If any of the situations mentioned above occur for the first time during the use of Vagirux, discontinue treatment and consult your doctor immediately.

Warnings and Precautions

Consult your doctor if you have or have had any of the following problems before starting treatment, as they may return or worsen during treatment with Vagirux. If so, consult your doctor more frequently for medical examinations.

• Fibroids inside the uterus;
• Thickening of cells that cover the uterus (endometriosis) or a history of excessive thickening of cells that cover the uterus (endometrial hyperplasia);
• High risk of developing blood clots (see "Blood clots in a vein (thrombosis)";
• High risk of developing estrogen-dependent cancer (such as having a mother, sister, or grandmother who has had breast cancer);
• High blood pressure;
• Liver disorders such as benign liver tumors;
• Diabetes;
• Stones in the gallbladder (biliary calculi);
• Migraine or severe headaches;
• A disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE);
• Epilepsy;
• Asthma;
• A disease that affects the eardrum and ear (otosclerosis);
• High levels of fat in the blood (triglycerides);
• Fluid retention due to heart or kidney problems;
• Hereditary and acquired angioedema.

Stop treatment with Vagirux and visit your doctor immediately

If you experience any of the following situations when using THS:

• any of the situations detailed in the previous section "Do not use Vagirux";
• 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 suggests angioedema;
• a significant increase in your blood pressure (symptoms may include headache, fatigue, and dizziness);
• migraine-type headache for the first time;
• if you become pregnant;
• if you notice signs of a blood clot, such as:

• inflammation with pain and redness of the legs,
• sudden chest pain,
• difficulty breathing.

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

Note:Vagirux is not a contraceptive. If it has been less than 12 months since your last menstrual period or you are under 50 years old, you may need to continue using additional contraceptive methods to avoid pregnancy. Consult your doctor for advice.

THS and Cancer

Endometrial hyperplasia and endometrial cancer

The prolonged use of estrogen-only THS tablets may increase the risk of developing endometrial cancer (cancer of the lining of the uterus).

It is not clear if there is a similar risk with Vagirux when used for repeated or long-term treatments (more than one year). However, Vagirux has shown very low absorption in the blood, and therefore, the addition of a progestogen is not necessary.

Do not worry if you experience bleeding or spotting. However, consult your doctor. It could be a sign of endometrial hyperplasia.

The following risks apply to hormone replacement therapy (HRT) that circulates in the blood. However, Vagirux is for local treatment in the vagina, and blood absorption is very low. It is less likely that the situations mentioned below will worsen or recur during treatment with Vagirux, but you should consult your doctor if you are concerned.

Breast Cancer

The evidence suggests that using Vagirux does not increase the risk of breast cancer in women who have not had breast cancer in the past. It is not known if Vagirux can be used safely in women who have had breast cancer in the past.

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

• furrows or creases in the skin.
• changes in the nipple.
• any lump that you can see or feel.

Additionally, it is recommended to participate in breast cancer screening programs when offered.

Ovarian Cancer

Ovarian cancer is rare, much rarer than breast cancer. The use of estrogen-only HRT has been associated with a slightly higher risk of ovarian cancer.

Comparison

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who are not using HRT, about 2 women per 2,000 will be diagnosed with ovarian cancer over a 5-year period. In women who have been using HRT for 5 years, there will be approximately 3 cases per 2,000 users (i.e., about 1 additional case).

Effect of HRT on the Heart and Circulation

Blood clots in a vein (thrombosis)

The risk of 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 treatment.

Blood clots can be serious and if one of them reaches the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

You are more likely to develop blood clots as you get older and if any of the following apply to you. Inform your doctor if you experience any of the following situations:

• if you are unable to walk for a long time due to major surgery, injury, or illness (see also section 3, if you are to undergo surgery)
• if you have significant obesity (BMI >30 kg/m2)
• if you have a blood clotting disorder that requires prolonged treatment with a medication to prevent blood clots
• if a close relative has ever had a blood clot in the legs, lungs, or other organs
• if you have systemic lupus erythematosus (SLE)
• if you have cancer

In case of signs of blood clots, see "Stop treatment with Vagirux and visit your doctor immediately".

Comparison

In women in their fifties who are not using HRT, it is expected that a mean 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 fifties who have been using HRT with estrogen-only for more than 5 years, it will be 5 to 8 cases per 1,000 users (i.e., about 1 additional case).

Heart Disease (Heart Attack)

In women who are using estrogen-only HRT, there is no increased risk of heart disease.

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 use increases with age.

Comparison

In women in their fifties who are not using HRT, a mean of 8 out of 1,000 will suffer a stroke over a 5-year period.

In women in their fifties who are using HRT, there will be 11 cases per 1,000 users over a 5-year period (about 3 additional cases).

Other Conditions

HRT does not prevent memory loss. The risk of probable memory loss may be slightly higher in women who start using some type of HRT after the age of 65. Consult your doctor.

Using Vagirux with Other Medications

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription, herbal remedies, or other natural products. However, Vagirux is used for local treatment in the vagina and is unlikely to affect other medications. Vagirux may affect other treatments applied vaginally.

Fertility, Pregnancy, and Breastfeeding

Vagirux is for use in postmenopausal women. If you become pregnant, discontinue use of Vagirux and contact your doctor immediately.

Driving and Operating Machines

Unknown.

Follow exactly the medication administration instructions indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Medication use

In the "INSTRUCTIONS FOR USE" section at the end of this leaflet, you will be told how to do it. Read the instructions carefully before using Vagirux.

The applicator is designed for multiple use, up to 24 times for a single patient (one vaginal tablet per application). After that, dispose of the applicator in household waste. Do not use applicators that show obvious signs of deterioration.

Frequency of use

• Apply one vaginal tablet daily for the first two weeks
• Subsequently, apply one vaginal tablet twice a week. There should be a gap of 3 or 4 days between each application.

General information about the treatment of menopausal symptoms

If you use more Vagirux than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service. Phone 915 620 420, indicating the medication and the amount used.

If you forget to use Vagirux

If you interrupt treatment with Vagirux

Do not stop treatment with Vagirux without consulting your doctor. Your doctor will explain the effects of stopping treatment. They will discuss other treatment options with you.

If you are to undergo surgery

If you are to undergo a surgical procedure, inform the surgeon that you are using Vagirux. You may need to stop using Vagirux for 4 to 6 weeks before the operation to reduce the risk of blood clots (see section 2, "Blood clots in a vein”). Ask your doctor when you can start using Vagirux again.

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

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

The following disorders have been reported more frequently in women using THS medications that circulate in the blood compared to women who do not use THS. These risks are less common in treatments administered vaginally, such as Vagirux:

For more information on these side effects, see section 2, “What you need to know before starting to use Vagirux”.

Frequent: can affect up to 1 in 10 people

Rare: can affect up to 1 in 100 people

Very rare: can affect up to 1 in 10,000 people

The following side effects have been reported with systemic estrogen treatment:

• skin discoloration, especially on the face or neck, known as “pregnancy mask” (melasma)
• red, painful nodules on the skin (erythema nodosum)
• skin eruptions with red inflammation or sores (erythema multiforme)

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Store the blister in the outer packaging to protect it from light.

Do not usethis medicationafter the expiration date that appears onthe packagingafter CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash.Deposit the packaging and medicines you no longer need at the SIGRE collection pointof the pharmacy.Ask your pharmacisthow to dispose ofthe packaging and medicines you no longerneed.This will help protect the environment.

What Vagirux contains

• The active ingredient is estradiol. Each vaginal tablet contains estradiol hemihydrate equivalent to 10 micrograms of estradiol.
• The other components are: hypromellose, lactose monohydrate, cornstarch and magnesium stearate.
• The coating contains: hypromellose and macrogol.

Appearance of the product and contents of the pack

The vaginal tablets are white, coated, biconvex, engraved with an E on one of their faces. The diameter of the tablet is approximately 6 mm.

Size of the packs:

18 vaginal tablets with applicator

24 vaginal tablets with applicator

Not all pack sizes may be marketed.

Marketing authorisation holder:

Gedeon Richter Plc.

Gyömroi út 19-21

1103 Budapest

Hungary

Manufacturer:

Gedeon Richter Plc.

Gyömroi út 19-21

1103 Budapest

Hungary

Haupt Pharma Münster GmbH (Member of the Aenova Group)

Schleebrüggenkamp 15

48159 Münster

Germany

Further information about this medicinal product can be obtained from the representative of the marketing authorisation holder in your country:

Gedeon Richter Ibérica, S.A.

Sabino Arana, 28 - 4º 2ª

08028 Barcelona

Spain

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Austria:Rewellfem 10MikrogrammVaginaltabletten

Croatia: Vagirux 10 mikrograma tablete za rodnicu

Denmark, Iceland, Liechtenstein: Rewellfem

Slovakia:Vagirux 10 mikrogramov vaginálne tablety

Slovenia: VAGIRUX 10 mikrogramov vaginalne tablete

Spain: Vagirux 10 microgramos comprimidos vaginales

Estonia,Finland,Ireland,Italy, Norway,Poland,Sweden,Czech Republic:Vagirux

Hungary: VAGIRUX 10 mikrogramm hüvelytabletta

Latvia:Vagirux10 mikrogramivaginalas tabletes

Lithuania:VAGIRUX10mikrogramu makštiestabletes

Malta:Vagirux 10 microgram vaginal tablets

Portugal: Formyra

Romania: ESTRADIOL RICHTER 10 micrograme comprimate vaginale

Last update of the summary of product characteristics:April 2022

Other sources of information

The 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/

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HOW TO USE VAGIRUX

How to use Vagirux

1. Remove the applicator from the blister pack that contains it.

Open by the end as shown in the image.

1. Hold the tube and pull the plunger of the applicator until it stops. Place a vaginal tablet in the support (wide end) of the tube of the applicator.

1. The applicator must be inserted carefully into the vagina until you feel some resistance (8-10 cm).

1. To release the vaginal tablet, press the plunger until it stops. The tablet will stick to the vaginal wall immediately. It will not fall off if the patient stands up or walks.

5.After each use, and before the next application, clean the applicator as follows:

• Remove the plunger from the applicator;
• clean both the tube and the plunger with mild soap and rinse them well with warm tap water. Rinse the inside and outside of the tube.
• if necessary, remove any remaining water from the tube and plunger by gently shaking them.
• dry the tube and plunger in the air on a clean surface (e.g. a paper towel)
• reinsert the plunger and tube into the applicator

6.The applicator should be used until the pack is finished (18 or 24 times).Then, throw it away.