VAGIRUX 10 micrograms vaginal tablets

Introduction

Package Leaflet: Information for the User

Vagirux 10 micrograms vaginal tablets

estradiol

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again. If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Vagirux and what is it used for
2. What you need to know before you use Vagirux
3. How to use Vagirux
4. Possible side effects
5. Storage of Vagirux

Contents of the pack and other information

1. What is Vagirux and what is it used for

Vagirux contains estradiol.

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

Vagirux belongs to a group of medicines called Hormone Replacement Therapy (HRT) vaginal.

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

Vagirux worksby replacing the estrogen normally produced by the ovaries in women. It is inserted into the vagina, so that the hormone is released where it is needed. This can relieve discomfort in the vagina.

2. What you need to know before you use Vagirux

Medical history and regular check-ups

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

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

Before starting (or resuming) HRT, your doctor will ask you about your family medical history. Your doctor may decide to perform a physical examination. This may include a breast examination and/or internal examination, if necessary.

Once you have started using Vagirux, you should see your doctor for check-ups at least once a year. During these check-ups, discuss with your doctor the benefits and risks of continuing with Vagirux.

Go for regular breast examinations as directed by your doctor.

Do not use Vagirux

If you are in any of the following situations. If you are not sure about any of the following conditions, consult your doctorbefore 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 estrogen-dependent cancer, such as cancer of the cells lining the uterus (endometrium), or if it is suspected that you may have it
• if you have abnormal vaginal bleeding
• if you have excessive growth of the cells lining the uterus (endometrial hyperplasia) that is not being treated.
• if you have or have had blood clots in the veins (thrombosis) in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
• if you have a blood clotting disorder (such as protein C, protein S, 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.
• 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, which is inherited from parents to children
• if you are allergic (hypersensitive) to estradiol or any of the other ingredients of Vagirux (listed in section 6 "Contents of the pack and other information")

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

Warnings and precautions

Consult your doctor if you suffer or have suffered from 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 in the uterus;
• Thickening of the cells lining the uterus (endometriosis) or a history of excessive thickening of the cells lining the uterus (endometrial hyperplasia);
• High risk of developing blood clots (see "Blood clots in a vein (thrombosis)");
• High risk of developing an 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;
• Gallstones (cholelithiasis);
• 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 membrane of the eardrum and the ear (otosclerosis);
• A high level 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 HRT:

• any of the situations detailed in the previous section "Do not use Vagirux";
• yellowing of the skin or the whites of the eyes (jaundice). It can be a symptom of liver disease;
• swelling of the face, tongue, or throat, and difficulty swallowing or urticaria accompanied by difficulty breathing, which suggest angioedema;
• a large increase in your blood pressure (symptoms can be 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 of age, you may still need to use additional contraceptive methods to prevent pregnancy. Consult your doctor for advice.

HRT and cancer

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

The prolonged use of HRT tablets with estrogens alone may increase the risk of developing endometrial cancer (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 into the bloodstream, and therefore, the addition of a progestogen is not necessary.

It is not a concern if you experience bleeding or spotting, however, consult your doctor. It could be a sign of endometrial thickening.

The following risks apply to Hormone Replacement Therapy (HRT) medications that circulate 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 reappear during treatment with Vagirux, but you should consult your doctor if you are concerned.

Breast cancer

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. Visit your doctor if you detect any changes such as:

• grooves or folds in the skin.
• changes in the nipple.
• any lump that you can see or feel.

In addition, it is recommended to participate in breast examination programs when they are offered.

Ovarian cancer

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

Comparison

The risk of ovarian cancer varies with age. For example, in women between 50 and 54 years old who do not use HRT, about 2 women out of 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 the 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 reaches the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

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

• if you cannot walk for a long time due to major surgery, injury, or illness (see also section 3, if you need to have surgery)
• if you are significantly overweight (BMI >30 kg/m2)
• if you have a blood clotting disorder that requires prolonged treatment with a medicine 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 about 4 to 7 out of 1,000 will have a blood clot in a vein over a 5-year period.

Regarding women in their fifties who have been using HRT with estrogens alone for more than 5 years, it will be 5 to 8 cases per 1,000 users (i.e., one additional case).

Heart disease (heart attack)

In women 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 do not use HRT, an average of 8 out of 1,000 will have a stroke over a 5-year period.

In women in their fifties who use HRT, there will be 11 cases per 1,000 users over a 5-year period (up to 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 HRT after the age of 65. Consult your doctor.

Using Vagirux with other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained 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 medicines. Vagirux may affect other vaginal treatments.

Fertility, pregnancy, and breastfeeding

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

Driving and using machines

None known.

3. How to use Vagirux

Follow the instructions for administration of the medicine indicated by your doctor. Consult your doctor or pharmacist if you have doubts.

Using the medicine

• You can start using Vagirux on the day that suits you best.
• For vaginal use only. Do not take the tablet orally.
• Insert the vaginal tablet into your vagina with the applicator.

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

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

Frequency of use

• Apply one vaginal tablet every day for the first two weeks
• Then apply one vaginal tablet twice a week. There should be 3 or 4 days between each application.

General information on the treatment of menopausal symptoms

• Your doctor will prescribe the lowest dose of Vagirux necessary to treat your symptoms for as long as necessary. Consult your doctor if you think this dose is too strong or not strong enough.
• Treatment should only be continued if the benefit outweighs the risk. Consult your doctor about this.

If you use more Vagirux than you should

• If you have used more Vagirux than you should, consult your doctor or pharmacist
• Vagirux is used for local treatment in the vagina. The dose of estradiol is so low that you would need to use a considerable number of tablets to achieve the dose normally used for oral treatment.

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

If you forget to use Vagirux

• If you forget a dose, use the medicine as soon as you remember
• Do not use a double dose to make up for forgotten doses.

If you stop 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 need to have surgery

If you are going to have surgery, inform the surgeon that you are using Vagirux. You may need to stop using Vagirux 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 questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• stroke;
• probable memory loss if HRT is started after the age of 65;

For more information on these side effects, see section 2, "What you need to know before you use Vagirux"

Common: may affect up to 1 in 10 people

• headache
• stomach pain

• vaginal bleeding, discharge, or discomfort

Uncommon: may affect up to 1 in 100 people

• genital fungal infection
• nausea
• skin rash
• weight gain
• hot flashes
• high blood pressure

Rare: may affect up to 1 in 1,000 people

• diarrhea
• fluid retention
• worsening of migraine
• generalized hypersensitivity (e.g., anaphylactic reaction or shock)

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

• gallbladder disease
• various skin disorders

• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma)
• red, painful skin nodules (erythema nodosum)
• skin rashes with red, inflamed areas or blisters (erythema multiforme)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects that are not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Vagirux

Keep this medication out of sight and reach of children.

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

Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of the indicated month.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and unused medications at the SIGRE Point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

What Vagirux contains

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

Appearance of the product and package contents

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

Package sizes:

18 vaginal tablets with applicator

24 vaginal tablets with applicator

Not all package sizes may be marketed.

Marketing authorization 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

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Gedeon Richter Ibérica, S.A.

Sabino Arana, 28 - 4º 2ª

08028 Barcelona

Spain

This medication is authorized in the member states of the European Economic Area under the following names:

Austria: Rewellfem 10 Mikrogramm Vaginaltabletten

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: Vagirux 10 mikrogrami vaginalas tabletes

Lithuania: VAGIRUX 10 mikrogramu makšties tabletes

Malta: Vagirux 10 microgram vaginal tablets

Portugal: Formyra

Romania: ESTRADIOL RICHTER 10 micrograme comprimate vaginale

Date of the last revision of this leaflet:April 2022

Other sources of information

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

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INSTRUCTIONS FOR USE

How to use Vagirux

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

Open it at the end as shown in the image.

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

1. The applicator should be carefully inserted into the vagina until a certain resistance is felt (8-10 cm).

1. To release the vaginal tablet, the plunger should be pressed until it stops. The tablet will adhere to the vaginal wall immediately. It will not fall out if the patient stands or walks.

1. Clean the applicator after each use, and before the next application, 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 both the tube and the 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

1. The applicator should be used until the package is finished (18 or 24 times). After that, dispose of it in household waste.