Vagirux

Package leaflet: Information for the user

Vagirux 10 micrograms vaginal tablets

estradiol
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Vagirux is and what it is used for
2. What you need to know 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 naturally produced by the ovaries.

Vagirux belongs to a group of medicines used for vaginal Hormone Replacement Therapy (HRT).
Vagirux is used to relieve menopausal symptoms such as vaginal irritation or dryness.
Medically, this condition is known as "atrophic vaginitis". It is caused by a decrease in estrogen levels in the body, which occurs naturally after menopause.
Vagirux works by replacing the estrogen normally produced by women's ovaries. It is inserted into the vagina so that the hormone is released where needed, thus relieving vaginal discomfort.

2. What you should know before using Vagirux

Medical history and regular medical check-ups
The use of HRT (hormone replacement therapy) involves 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 treatment) is limited. If you have premature menopause, the risk associated with using HRT may differ. Please discuss this with your doctor.
Before starting (or restarting) HRT, your doctor will ask about your personal and family medical history. Your doctor may decide to perform a physical examination, which could include a breast examination or an internal examination, if necessary.
Once you have started treatment with Vagirux, you should see your doctor for follow-up visits at least once a year. During these check-ups, discuss with your doctor the benefits and risks of continuing treatment with Vagirux.
Perform regular breast monitoring as recommended by your doctor.

Do not use Vagirux:
If you are in any of the following conditions. If you are unsure about any of the points listed below, talk to your doctor before using Vagirux.

Do not use Vagirux:

• If you have or have had breast cancer or there is suspicion of it.
• If you have or have had, or there is suspicion of, an estrogen-dependent tumor, such as cancer of the uterine lining (endometrium).
• If you have unexplained vaginal bleeding.
• If you have untreated excessive growth of the uterine lining (endometrial hyperplasia).
• If you have or have had blood clots in the veins (thrombosis), such as in the legs (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 recently had an arterial disorder caused by blood clots, such as heart attack, stroke, or angina.
• If you have or have had a liver disorder and your liver function tests have not returned to normal.
• If you have a rare inherited blood disease called “porphyria”.
• If you are allergic to estradiol or any of the other ingredients of this medicine (listed in section 6).

If any of the above conditions occur for the first time while using Vagirux, stop taking it immediately and consult your doctor without delay.

Warnings and precautions
Before starting treatment, talk to your doctor if you have or have had any of the following conditions, as they may recur or worsen during treatment with Vagirux. If so, your doctor may need to see you more frequently for medical check-ups.

• Uterine fibroids;
• Growth of the uterine lining outside the uterus (endometriosis) or history of excessive growth of the uterine lining (endometrial hyperplasia);
• Increased tendency to form blood clots (see “Blood clots in a vein (thrombosis)”);
• Increased risk of estrogen-dependent tumors (such as having a mother, sister, or grandmother who had breast cancer);
• High blood pressure;
• Liver disorder such as benign liver tumor;
• Diabetes;
• Gallstones;
• Migraine or severe headache;
• An autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE);
• Epilepsy;
• Asthma;
• A disorder of the ear and hearing (otosclerosis);
• Very high levels of fats in the blood (triglycerides);
• Fluid retention due to heart or kidney problems;
• Hereditary or acquired angioedema.

Stop using Vagirux and consult your doctor immediately if you experience any of the following while using HRT:

• Any condition listed in the section “Do not use Vagirux”;
• Yellowing of the skin and eyes (jaundice). These could be signs of a liver disorder;
• Swelling of the face, tongue, and/or throat and/or difficulty swallowing or hives with breathing difficulties, which are indicative of angioedema;
• Significant increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• A new type of migraine headache you have never had before;
• If you become pregnant;
• If you notice signs of blood clots 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: 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, you still need to use additional contraception to prevent pregnancy. Consult your doctor for advice.

HRT and cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Long-term treatment with estrogen-only therapy may increase the risk of developing cancer of the uterine lining (endometrium).
It is not certain whether there is a similar risk with Vagirux when used repeatedly or for prolonged periods (more than one year). However, Vagirux has shown very low absorption into the bloodstream, and therefore the addition of a progestogen is not necessary.

If you experience vaginal bleeding or spotting, this is usually not a cause for concern, but you should schedule an appointment with your doctor. It could be a sign of endometrial thickening.

The following risks are associated with systemic HRT (hormone replacement therapy) that circulates in the blood. However, Vagirux is used for local vaginal treatment and systemic absorption is very low. It is therefore less likely that the conditions listed below will worsen or reappear during treatment with Vagirux. Nevertheless, contact your doctor if you have any doubts.

Breast cancer
Evidence suggests that the use of Vagirux does not increase the risk of breast cancer in women who have not previously had this type of cancer. It is not known whether Vagirux can be safely used in women who have previously had breast cancer.

Regularly check your breasts. Contact your doctor if you notice any changes such as:

• Dimpling of the skin;
• Changes in the nipple;
• Any lumps you see or feel.

In addition, it is recommended to participate in mammographic screening programs when offered.

Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. The use of estrogen-only therapy has been associated with a slight increase in the risk of ovarian cancer.

Comparative data
The risk of ovarian cancer varies with age. For example, among women aged 50–54 years who do not take HRT, about 2 out of 2,000 women will be diagnosed with ovarian cancer over a 5-year period. Among women who take HRT for 5 years, there are about 3 cases per 2,000 users (i.e., about 1 additional case).

Effect of HRT on heart and circulation

Blood clots in a blood vessel (thrombosis)
The risk of developing blood clots in a blood vessel is approximately 1.3 to 3 times higher in women taking HRT compared to women not taking HRT, particularly during the first year of treatment.
Blood clots can be serious; if a clot reaches the lungs, it can cause chest pain, shortness of breath, collapse, or even death.

The likelihood of developing blood clots in blood vessels increases with age and if one or more of the following conditions apply to you. Inform your doctor in any of the following cases:

• If you cannot walk or must remain immobilized for a long time due to surgery, trauma, or illness (see also section 3, “If you need surgery”)
• If you are significantly overweight (BMI > 30 kg/m²)
• If you have a clotting disorder for which you have required long-term treatment with a medicine used to prevent clots
• If you or a close relative has previously had a blood clot in the leg, lung, or another organ
• If you have systemic lupus erythematosus (SLE)
• If you have a tumor

For signs of blood clots, see “Stop using Vagirux and consult your doctor immediately”.

Comparative data
Among women aged 50 years who do not take HRT, on average 4 to 7 cases of blood clots in a blood vessel per 1,000 women might be expected over a period of more than 5 years.
Among women aged 50 years who use estrogen-only HRT for 5 years, 5 to 8 cases per 1,000 users are diagnosed (one additional case).

Heart disorders (heart attack)
In women using estrogen-only HRT, there is no increased risk of developing heart disorders.

Stroke
The risk of stroke is approximately 1.5 times higher in women taking HRT compared to women not taking HRT. The number of additional stroke cases due to HRT use increases with advancing age.

Comparative data
Among women aged 50 years who do not take HRT, on average 8 cases per 1,000 might be expected over a period of more than 5 years. For women aged 50 years who take HRT for more than 5 years, 11 cases per 1,000 users are diagnosed (3 additional cases).

Other conditions
HRT does not have a preventive effect on memory loss. The risk of possible memory loss may be slightly higher in women who start any type of HRT after the age of 65. Talk to your doctor.

Other medicines and Vagirux
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription, herbal remedies, or other natural products.
However, Vagirux is used for local vaginal treatment and does not interfere with the use of other systemic medications.
Vagirux may affect other treatments applied vaginally.

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

Driving and using machines
No known effects.

3. How to use Vagirux

Use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor or pharmacist.
Use of this medicine

• You may start treatment with Vagirux on any day that is convenient for you.
• For vaginal use only. Do not take the tablet by mouth.
• Insert the vaginal tablet into the vagina using the applicator.

The 'INSTRUCTIONS FOR THE USER' at the end of this leaflet will show you how to do this. Read
the instructions carefully before using Vagirux.
The vaginal tablet applicator is intended for multiple use, up to 24 times for a single
patient (one tablet per application). After that, dispose of the applicator through household
waste. Do not use applicators showing obvious signs of damage.
Dosage

• Use one vaginal tablet daily for the first 2 weeks.
• Then use one vaginal tablet twice a week. Allow 3 or 4 days between each dose.

General information on the treatment of menopausal symptoms

• Your doctor will aim to prescribe the lowest effective dose of Vagirux to treat your symptoms for the shortest possible duration. Speak with your doctor if you think this dose is too high or not strong enough.
• Treatment should continue only if the benefits outweigh the risks. Consult your doctor about this.

If you use more Vagirux than you should

• If you have used more Vagirux than prescribed, consult your doctor or pharmacist.
• Vagirux is intended for local internal vaginal treatment. The dose of estradiol is so low that a considerable number of tablets would need to be taken to reach the dose normally administered with oral treatment.

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 the missed dose.

If you stop using Vagirux
Do not stop using Vagirux without first consulting your doctor. Your doctor will explain the effects
of stopping treatment and discuss with you other possible treatment options.
If you are due to have surgery
If you are scheduled for surgery, inform your surgeon that you are using Vagirux. It may be necessary
to stop using Vagirux 4 to 6 weeks before surgery to avoid the risk of blood clots (see section 2, Blood clots in a blood vessel). Ask your doctor when you can start using Vagirux again.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this one may cause side effects, although not everyone experiences them.
The following conditions are reported more frequently in women using systemic hormone replacement therapy (HRT) circulating in the blood compared to women not using HRT. These risks are lower with vaginal treatments such as Vagirux:

• ovarian cancer;
• blood clots in a blood vessel of the legs or lungs (venous thromboembolism);
• stroke;
• possible memory loss in women who start any type of HRT after the age of 65.

For further information on these side effects, see section 2, ‘What you should know before using Vagirux’.
Common: may affect more than 1 in 10 people

• Headache
• Stomach ache
• Vaginal bleeding, discharge and discomfort.

Uncommon: may affect more than 1 in 100 people

• Fungal infections of the genitals
• Malaise (nausea)
• Rash
• Weight gain
• Hot flushes
• Hypertension

Very rare: may affect more than 1 in 10,000 people

• Diarrhoea
• Fluid retention
• Worsening of migraine
• Generalised hypersensitivity (e.g. anaphylactic reactions/shock).

The following side effects have been reported with systemic oestrogen therapy:

• Cholelithiasis
• Various skin disorders:
  • skin discolouration, particularly on the face and neck, known as “pregnancy mask” (chloasma)
  • painful red skin nodules (erythema nodosum)
  • skin erythema with redness and sores (erythema multiforme).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vagirux

Keep this medicine out of the sight and reach of children.
Keep the blister pack in the outer cardboard packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the carton label and on the blister after EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.
This medicine may pose a risk to the aquatic environment.

6. Package contents and other information

What Vagirux contains

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

Description of the appearance of Vagirux and contents of the pack
The vaginal tablets are white, round, film-coated tablets with an "E" imprinted on one side. The tablet diameter is approximately 6 mm.
Pack sizes:
18 vaginal tablets with reusable applicator.
24 vaginal tablets with reusable applicator.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
Budapest H-1103
Hungary

Manufacturer
Haupt Pharma Münster GmbH (Member of the Aenova Group)
Schleebrüggenkamp 15
48159 Münster
Germany
Gedeon Richter Plc.
Gyömrői út 19-21.
Budapest H-1103
Hungary

This medicinal product is authorised in the European Economic Area countries under the following names:
AT Rewellfem 10 Mikrogramm Vaginaltabletten
CZ Vagirux
DK Rewellfem
EE Vagirux
ES Vagirux 10 microgram vaginal tablets
FI Vagirux
HR Vagirux 10 mikrograma tablete za rodnicu
HU Vagirux 10 mikrogramm hüvelytabletta
IE Vagirux
IS Rewellfem
IT Vagirux
LI Rewellfem
LT VAGIRUX 10 mikrogramų makšties tabletės
LV Vagirux 10 mikrogrami vaginālās tabletes
MT Vagirux 10 microgram vaginal tablets
NO Vagirux
PL Vagirux
PT Formyra
RO ESTRADIOL RICHTER 10 micrograme comprimate vaginale
SE Vagirux
SI Vagirux 10 mikrogramov vaginalne tablete
SK Vagirux 10 mikrogramov vaginálne tablety
<------------------------------------------------------------------------------------------------------------------------>
USER INSTRUCTIONS
How to use Vagirux

1. Remove the applicator from its packaging. Open the end as shown in the figure.

2. While holding the tube, pull the plunger of the applicator until it stops. Press a vaginal tablet out of the separate blister and place it securely into the holder (the wider end) of the applicator tube.

3. Carefully insert the applicator into the vagina. Stop when resistance is met (8–10 cm).

4. To release the tablet, gently press the button until it stops. The tablet is thus immediately deposited against the vaginal wall. It will not fall out when standing or walking.

5. After each use, before subsequent use, clean the applicator according to the following cleaning procedure:

   • Remove the plunger from the applicator.
   • Clean the tube and plunger with neutral soap and thoroughly rinse with warm tap water. Rinse both the inner and outer surfaces of the tube.
   • If necessary, remove excess residual water from both the tube and plunger by briefly shaking them.
   • Allow both the tube and plunger to air-dry on a clean surface (e.g. a paper towel).
   • Reinsert the plunger into the applicator tube for future use.

6. Use the applicator until the pack is empty (18 or 24 times). Afterwards, dispose of it in household waste.