Vagirux

Package leaflet: Information for the user

Vagirux, 10 micrograms, vaginal tablets
Estradiolum
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

1. What Vagirux is and what it is used for
2. Important information before using Vagirux
3. How to use Vagirux
4. Possible side effects
5. How to store Vagirux
6. Contents of the pack and other information

1. What Vagirux is and what it is 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 a woman's ovaries.

Vagirux belongs to a group of medicines known as local estrogen replacement therapy (ERT) administered vaginally.
Vagirux is used to relieve menopausal symptoms in the vagina, such as dryness or irritation. In medical terminology, this condition is known as "atrophic vaginitis". It is caused by a decrease in estrogen levels in the body and occurs naturally after menopause.
Vagirux works by replacing the estrogen normally produced by a woman's ovaries. The medicine is administered vaginally, so the hormone is released exactly where it is needed. This may help relieve vaginal discomfort.

2. Important information before using Vagirux

Medical history and regular check-ups
Hormone replacement therapy (HRT) carries risks that should be considered when a woman decides whether to start or continue HRT.
Experience in treating women during premature menopause (due to ovarian failure or surgical intervention) is limited. If a woman experiences premature menopause, the risks associated with HRT may differ. Please discuss this with your doctor.
Before starting (or resuming) HRT, your doctor should take a full medical and family history. Your doctor may decide to perform examinations such as a breast examination and/or gynecological examination, if necessary.
If you start using Vagirux, you should consult your doctor at least once a year. During follow-up visits, you should discuss with your doctor the benefits and risks of continuing Vagirux treatment.
Women should undergo regular breast screening examinations as recommended by their doctor.

When not to use Vagirux
If any of the conditions listed below are present or you have concerns related to them, you must consult your doctor before starting Vagirux.
Do not use Vagirux if you:

• have been diagnosed with, have had in the past, or are suspected of having breast cancer;
• have been diagnosed with, have had in the past, or are suspected of having an estrogen-dependent tumor, such as endometrial cancer (cancer of the lining of the womb);
• have unexplained vaginal bleeding;
• have excessive thickening of the lining of the womb (endometrial hyperplasia) that has not been treated;
• have been diagnosed with or have had in the past blood clots in the veins (venous thromboembolism), e.g., in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency);
• currently have or recently had an arterial disease caused by blood clots, e.g., heart attack, stroke, or angina pectoris;
• have liver disease and liver function tests have not returned to normal;
• have a rare inherited blood disorder - porphyria;
• are allergic to estradiol or any of the other ingredients of Vagirux (listed in section 6).

If any of the above conditions occur for the first time while using Vagirux, stop using the medicine immediately and contact your doctor as soon as possible.

Warnings and precautions
Before starting treatment, inform your doctor if you currently have or have had any of the following conditions, as they may recur or worsen during treatment with Vagirux. In such cases, your doctor may decide that more frequent monitoring is necessary.

• Uterine fibroids;
• Endometriosis (presence of uterine lining tissue outside the uterus) or previous excessive endometrial proliferation (endometrial hyperplasia);
• Increased risk of venous blood clots (see “Blood clots in veins (venous thrombosis)”);
• Increased risk of estrogen-dependent tumors (e.g., history of breast cancer in mother, sister, or grandmother);
• High blood pressure;
• Liver disease, e.g., benign liver tumor;
• Diabetes;
• Gallstones;
• Migraine or severe headaches;
• Autoimmune disease affecting multiple organs – systemic lupus erythematosus;
• Epilepsy;
• Asthma;
• Otosclerosis (a disease affecting the ear drum and hearing);
• Very high levels of fats (triglycerides) in the blood;
• Fluid retention due to impaired heart or kidney function;
• Hereditary or acquired angioedema.

You must stop using Vagirux and contact your doctor immediately if any of the following conditions occur during HRT treatment:

• Development of any of the conditions listed under “When not to use Vagirux” above;
• Yellowing of the skin or eyes (jaundice). These may be symptoms of liver disease;
• Swelling of the face, tongue, and/or throat and/or difficulty swallowing, or hives together with breathing difficulties, suggesting angioedema;
• Significant increase in blood pressure (symptoms include headache, fatigue, and dizziness);
• New-onset migraine headache;
• If you become pregnant;
• If you develop symptoms of blood clots such as:
  • painful swelling and redness in the legs,
  • sudden chest pain,
  • difficulty breathing. For more information, see “Blood clots in veins (venous thrombosis)”.

Note: Vagirux is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, additional contraception may be necessary. Please consult your doctor.

HRT and cancer

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)
Long-term use of oral HRT containing only estrogens may increase the risk of developing cancer of the lining of the womb (endometrium).
It is not known whether a similar risk exists with repeated or prolonged use (longer than one year) of Vagirux. However, Vagirux is absorbed into the bloodstream to a very small extent, and therefore adding a progestogen is not necessary.

Bleeding or spotting is usually not a cause for concern, but you should consult your doctor. It may be a sign of endometrial thickening.

The risks described above apply to HRT medicines that enter the bloodstream. Vagirux is applied locally into the vagina and is absorbed into the blood to a very small extent. It is less likely that the conditions listed below will worsen or recur during treatment with Vagirux. However, if you have any doubts, consult your doctor.

Breast cancer
Data indicate that using Vagirux does not increase the risk of developing breast cancer in women who have never had it before. It is not known whether Vagirux can be safely used in women who have had breast cancer.

You should regularly examine your breasts. Contact your doctor if you notice any of the following changes:

• skin indentation,
• changes in the nipple,
• presence of lumps that are visible or palpable.

Additionally, screening mammograms are recommended as advised by your doctor.

Ovarian cancer
Ovarian cancer is rare—much rarer than breast cancer. The use of estrogen-only HRT is associated with a slightly increased risk of ovarian cancer.

Comparison
The risk of ovarian cancer depends on age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over a 5-year period. Among women who have used HRT for 5 years, it occurs in about 3 out of 2000 women (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in veins (venous thrombosis)
The risk of venous blood clots is 1.3 to 3 times higher in women using HRT compared to non-users, especially during the first year of treatment.
Venous blood clots can have serious consequences, and if they travel to the lungs, they may cause chest pain, shortness of breath, loss of consciousness, or even death.

The risk of venous blood clots is higher if you are older or if any of the following apply to you. Inform your doctor if any of the following apply to you:

• you are unable to walk for a prolonged period due to major surgery, injury, or illness (see also section 3, “If surgery is planned”);
• you are significantly overweight (BMI > 30 kg/m²);
• you have thromboembolic disorders requiring long-term anticoagulant therapy;
• you or a close family member have previously had blood clots in the legs, lungs, or other organs;
• you have systemic lupus erythematosus;
• you have been diagnosed with cancer.

If you experience symptoms of blood clots, see “You must stop using Vagirux and contact your doctor immediately”.

Comparison
Among women aged 50 to 59 who do not use HRT, the number of venous blood clot cases over 5 years is estimated at 4 to 7 per 1000 women.
Among women aged 50 to 59 using estrogen-only HRT for more than 5 years, the number is 5 to 8 per 1000 women (i.e., 1 additional case).

Heart disease (heart attack)
Women using estrogen-only HRT do not have an increased risk of developing heart disease.

Stroke
The risk of stroke is about 1.5 times higher in women using HRT compared to non-users. The number of additional stroke cases caused by HRT increases with age.

Comparison
Among women aged 50 to 59 who do not use HRT, the number of stroke cases over 5 years is estimated at an average of 8 per 1000 women. Among women aged 50 to 59 using HRT, the number is 11 per 1000 women over 5 years (i.e., 3 additional cases).

Other conditions
HRT does not prevent memory loss. The risk of probable memory loss may be somewhat higher in women who start HRT after the age of 65. Consult your doctor.

Vagirux and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those available without a prescription, herbal remedies, or other natural products.
The likelihood of drug interactions is low because Vagirux is applied locally into the vagina. However, Vagirux may affect other local treatments applied vaginally.

Pregnancy and breastfeeding
Vagirux is intended for use only in postmenopausal women. If you become pregnant, stop using the medicine and contact your doctor.

Driving and operating machinery
The effect of Vagirux on driving or operating machinery is unknown.

3. How to use Vagirux

This medicine should always be used as directed by your doctor. If in doubt, consult your doctor or pharmacist.

How to use Vagirux

• Treatment with Vagirux may be started on any day.
• For vaginal use only. Do not take the tablets by mouth.
• A vaginal tablet should be inserted into the vagina using the applicator.

The “INSTRUCTIONS FOR USE” at the end of this leaflet provide detailed guidance. Before using Vagirux, read the instructions carefully.
The vaginal tablet applicator is intended for repeated use up to 24 times for one patient (one tablet per application). After this, the applicator should be discarded with household waste. Do not use applicators showing visible signs of damage.

What dose to use

• For the first 2 weeks, use one vaginal tablet once daily.
• Afterwards, use one vaginal tablet twice a week. Maintain a 3–4 day interval between doses.

General information about treatment of menopausal symptoms

• Your doctor will determine the lowest effective dose of Vagirux for the shortest possible duration needed to treat your symptoms. Consult your doctor if the prescribed dose seems too high or insufficient.
• Treatment should continue only if its benefits outweigh the risks. Discuss this with your doctor.

Using more than the recommended dose of Vagirux

• If you use more Vagirux than recommended, contact your doctor or pharmacist.
• Vagirux is intended for local, intravaginal use. The dose of estradiol is so low that a significant number of tablets would need to be used to reach the dose typically administered orally.

Missing a dose of Vagirux

• If you miss a dose, use the missed tablet as soon as possible.
• Do not use a double dose to make up for a missed dose.

Stopping treatment with Vagirux
Do not stop treatment with Vagirux without consulting your doctor. Your doctor will explain the consequences of stopping treatment and discuss other possible treatment options.

If surgery is planned
If you are scheduled for surgery, inform the surgeon that you are using Vagirux. It may be necessary to stop using Vagirux 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2, “Blood clots in veins (venous thrombosis)”).
Before restarting Vagirux, consult your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
In women using systemic HRT (hormone replacement therapy), the following conditions have been reported more frequently compared to women not using HRT. These risks are less relevant for locally administered medicines, such as Vagirux:

• ovarian cancer;
• blood clots in the legs or lungs (venous thromboembolic disease);
• stroke;
• possible memory loss, if HRT is started after the age of 65.

For further information, see section 2, "Important information before using Vagirux".

Common: may affect less than 1 in 10 women

• headache;
• abdominal pain;
• vaginal bleeding, discharge, or discomfort.

Uncommon: may affect less than 1 in 100 women

• fungal genital infections;
• malaise (nausea);
• rash;
• weight gain;
• hot flushes;
• hypertension.

Very rare: may affect less than 1 in 10,000 women

• diarrhoea;
• fluid retention;
• migraine worsening;
• generalized hypersensitivity (e.g. anaphylactic reaction/anaphylactic shock).

The following adverse effects have been reported during systemic estrogen therapy:

• gallbladder stones;
• various skin disorders:
• skin hypopigmentation, especially on the face or neck, known as chloasma (melasma);
• painful red nodules of the skin (erythema nodosum);
• rash with characteristic redness or pain (erythema multiforme).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C,
02-222 Warsaw,
tel.: +48 22 49 21 301,
fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the Marketing Authorisation Holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Vagirux

Keep this medicine out of sight and reach of children.
Store blisters in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the carton and blister after "Expiry date". The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. This medicine may pose a risk to the aquatic environment.

6. Contents of the packaging and other information

What Vagirux contains

• The active substance is estradiol. Each vaginal tablet contains estradiol hemihydrate equivalent to 10 micrograms of estradiol.
• Other ingredients are: hypromellose 15 mPa  s, monohydrate lactose, corn starch and magnesium stearate. Tablet coating: hypromellose 5 mPa  s and macrogol 6000.

What Vagirux looks like and contents of the pack
The vaginal tablets are white, round, coated, with the letter “E” engraved on one side, approximately 6 mm in diameter.
Pack sizes:
18 vaginal tablets in a blister made of PVC/PVDC/Aluminium foil, with a separately packaged reusable vaginal applicator made of LDPE/PP, protected by a PP foil. All contained in a cardboard box.
24 vaginal tablets in a blister made of PVC/PVDC/Aluminium foil, with a separately packaged reusable vaginal applicator made of LDPE/PP, protected by a PP foil. All contained in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
GEDEON RICHTER POLSKA Sp. z o.o.
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
Poland

Manufacturer
Haupt Pharma Münster GmbH
Schleebrüggenkamp 15
48159 Münster
Germany
Gedeon Richter Plc.
Gyömrői út 19-21.
Budapest 1103
Hungary

For further information about this medicinal product, please contact:
GEDEON RICHTER POLSKA Sp. z o.o.
Medical Department
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
tel. +48 (22)755 96 48
[email protected]

This medicinal product is authorised in the European Economic Area countries under the following names:
Hungary Vagirux 10 mikrogramm hüvelytabletta
Austria Rewellfem 10 Mikrogramm Vaginaltabletten
Liechtenstein Rewellfem
Czech Republic Vagirux
Slovakia Vagirux 10 mikrogramov vaginálne tablety
Denmark Rewellfem
Iceland Rewellfem
Norway Vagirux
Finland Vagirux
Sweden Vagirux
Estonia VAGIRUX
Latvia Vagirux 10 mikrogrami vaginālās tabletes
Lithuania VAGIRUX 10 mikrogramų makšties tabletės
Croatia Vagirux 10 mikrograma tablete za rodnicu
Slovenia Vagirux 10 mikrogramov vaginalne tablete
Ireland Vagirux
Malta Vagirux 10 microgram vaginal tablets
Spain Vagirux 10 microgram vaginal tablets
Italy Vagirux
Poland Vagirux
Portugal Formyra
Romania ESTRADIOL RICHTER 10 micrograme comprimate vaginale

DIRECTIONS FOR USE
How to use Vagirux

1. Remove the protective foil from the applicator. Open from the side indicated in the image.

2. Holding the tube, pull the plunger of the applicator until it stops. Take one vaginal tablet from the separate blister and place it firmly into the holder (the wider end) of the applicator tube.

3. Gently insert the applicator into the vagina until resistance is felt (8–10 cm).

4. To release the tablet, press the plunger until resistance is felt. The tablet will immediately adhere to the vaginal wall. There is no risk of the tablet falling out when standing or during walking.

5. After each use, before the next use, clean the applicator according to the cleaning instructions below:
   • Remove the plunger from the applicator.
   • Clean both the tube and the plunger using mild soap and thoroughly rinse with warm tap water. Rinse both the inner and outer surfaces of the tube.
   • If necessary, remove excess water remaining in both the tube and the plunger by shaking them briefly.
   • Allow both the tube and the plunger to air dry on a clean surface (e.g., on a paper towel).
   • Reinsert the plunger into the applicator tube for later use.
6. The applicator should be used until the pack is empty (18 or 24 times), then discarded with household waste.