Vagifem

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: information for the user

Vagifem, 10 micrograms, vaginal tablets

estradiol

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4, "Possible side effects".

Table of contents of the leaflet

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

1. What Vagifem is and what it is used for

Vagifem 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.

Vagifem belongs to a group of medicines known as hormone replacement therapy (HRT) for vaginal use.
It is usedto alleviate symptoms of menopause that occur in the vagina, such as dryness or irritation. In medical terminology, this phenomenon is called "atrophic vaginitis". It is caused by a decrease in estrogen levels in the body and naturally occurs after menopause.
Vagifem worksby replacing estrogen, which is produced by the ovaries in women. The medicine is administered vaginally, and the hormone is released where it is needed. This can alleviate discomfort in the vagina.
Experience with treating women over 65 years of age is limited.

2. Important information before using Vagifem

Medical history and regular check-ups

Using HRT involves risks that should be considered when the patient decides whether to use hormone replacement therapy or continue using it.
Experience with treating women in premature menopause (due to ovarian failure or surgery) is limited. If the patient is experiencing premature menopause, the risk associated with HRT may be different. Consult your doctor.
Before starting (or resuming) HRT, the doctor should take a medical history, including a family history. The doctor may decide to perform an examination, such as a breast examination and/or gynecological examination, if necessary.
If the patient starts using Vagifem, they should consult their doctor at least once a year. During follow-up visits, they should discuss the benefits and risks of continuing to use Vagifem with their doctor.
Patients should regularly perform breast screening tests in accordance with their doctor's recommendations.

When not to use Vagifem

In case of any of the following diseases or resulting doubts, consult your doctorbefore starting to use Vagifem.
Do not use Vagifem if the patient:

• has been diagnosed with allergy(hypersensitivity) to estradiolor any of the other ingredients of Vagifem (listed in section 6, "Contents of the pack and other information");
• has been diagnosed with, has had, or is suspected of having breast cancer;
• has been diagnosed with, has had, or is suspected of having estrogen-dependent tumors, such as endometrial cancer (cancer of the uterine lining);
• has been diagnosed with unexplained vaginal bleeding;
• has been diagnosed with excessive thickening of the uterine lining(endometrial hyperplasia) that has not been treated;
• has been diagnosed with or has had blood clots in the veins(thrombosis), such as in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• has a blood clotting disorder(such as protein C, protein S, or antithrombin deficiency);
• has had or recently had a disease caused by blood clots, such as heart attack, stroke, or angina pectoris;
• has been diagnosed with or has had liver diseaseand liver test results have not returned to normal;
• has been diagnosed with a rare blood disorder - porphyria, which is inherited.

If any of the above diseases occur for the first time while using Vagifem, stop using it 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 diseases, as they may recur or worsen while using Vagifem.
In such cases, your doctor may determine the need for more frequent check-ups.

• asthma;
• epilepsy;
• diabetes;
• gallstones;
• high blood pressure;
• migraine or severe headaches;
• liver disease, such as a benign liver tumor;
• endometriosis (growth of uterine lining outside the uterus) or excessive growth of uterine lining (endometrial hyperplasia) in the past;
• a disease affecting the eardrum and hearing - otosclerosis;
• a disease of the immune system that affects many organs - systemic lupus erythematosus;
• increased risk of estrogen-dependent tumors (breast cancer in the mother, sister, or grandmother);
• increased risk of blood clots (see "Blood clots in the veins (venous thromboembolism)");
• uterine fibroids;
• very high levels of fats (triglycerides) in the blood;
• fluid retention due to impaired heart or kidney function;
• hereditary and acquired angioedema.

Stop using Vagifem and contact your doctor immediatelyif any of the following conditions occur while using HRT:

• migraine headache that occurred for the first time;
• yellowing of the skin and eyes (jaundice), which may be symptoms of liver disease;
• swelling of the face, tongue, and/or throat, or difficulty swallowing or hives, along with difficulty breathing, which may indicate angioedema;
• significant increase in blood pressure (symptoms include headache, fatigue, and dizziness);
• occurrence of any of the diseases listed in the "When not to use Vagifem" section above;
• if the patient becomes pregnant;
• if the patient experiences symptoms of blood clots, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• difficulty breathing. For more information, see the "Blood clots in the veins (venous thromboembolism)" section.

Note: Vagifem is not a contraceptive. If it has been less than 12 months since the last menstrual period or the patient is under 50 years old, additional contraceptive methods may be necessary. Consult your doctor.

HRT and tumors

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

Long-term use of HRT tablets containing only estrogen may increase the risk of developing uterine lining cancer (endometrium).
It is not known whether a similar risk exists with repeated or prolonged (longer than one year) use of Vagifem. However, Vagifem is absorbed into the bloodstream to a very small extent, and therefore, the addition of progestogen is not necessary.
Bleedingor spottingis usually not a cause for concern, but consult your doctor. It may be a sign of endometrial hyperplasia.
The risks described below are related to HRT medications that circulate in the blood. Vagifem, on the other hand, is intended for local use in the vagina and is absorbed into the bloodstream to a very small extent. The worsening or recurrence of the following conditions during the use of Vagifem is less likely, but if you have any concerns, consult your doctor.

Breast cancer

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

Check your breasts regularly. Contact your doctor if you notice any of the following changes:

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

In addition, it is recommended to perform screening mammograms in accordance with your doctor's recommendations.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Using HRT that only contains estrogen is associated with a slightly increased risk of ovarian cancer.
Comparison
The risk of ovarian cancer depends on age. For example, in women between 50 and 54 years old who do not use HRT, ovarian cancer will be diagnosed within 5 years in about 2 out of 2000 women. In women who have used HRT for 5 years, it will occur in about 3 out of 2000 women (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in the veins (venous thromboembolism)

The risk of developing blood clots in the veinsis 1.3 to 3 times higher in women using HRT compared to those not using it, especially in the first year of use.
The formation of blood clots can have serious consequences, and if they move to the lungs, they can cause chest pain, shortness of breath, loss of consciousness, or even death.
The risk of blood clots in the veins is higher if the patient is older or if any of the following situations apply to the patient. Inform your doctor if any of the following situations apply to you:

• you are unable to walk for an extended period due to a serious operation, injury, or illness (see also section 3, "If surgery is planned");
• you have significant obesity (BMI > 30 kg/m2);
• you have thromboembolic disorders that require long-term use of medications to prevent blood clots;
• you or a close family member have had blood clots in the legs, lungs, or other organs in the past;
• you have systemic lupus erythematosus;
• you have been diagnosed with cancer.

If you experience symptoms of blood clots, see "Stop using Vagifem and contact your doctor immediately".
Comparison
In women between 50 and 59 years old who do not use HRT, the number of cases of blood clots in the veins within 5 years is estimated to be 4 to 7 per 1000 women.
In women between 50 and 59 years old who use estrogen-only HRT for more than 5 years, the number of cases will be 5 to 8 per 1000 (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 those not using it. The number of additional stroke cases caused by HRT increases with age.
Comparison
In women between 50 and 59 years old who do not use HRT, the number of stroke cases within 5 years is estimated to be 8 per 1000 women. In women between 50 and 59 years old who use HRT, the number of cases within 5 years will be 11 per 1000 women (i.e., 3 additional cases).

Other conditions

HRT does not prevent memory loss. The risk of possible memory loss may be slightly higher in women who start using HRT at an age over 65. Consult your doctor.

Vagifem and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those that are available without a prescription, herbal medicines, or other natural products. The likelihood of interactions with other medicines is low, as Vagifem is used locally in the vagina. Vagifem may affect other local treatments used in the vagina.

Pregnancy and breastfeeding

Vagifem is intended for use only in postmenopausal women. If the patient becomes pregnant, stop using the medicine and contact your doctor.

Driving and using machines

It is not known whether Vagifem affects driving or using machines.

3. How to use Vagifem

Always use this medicine exactly as your doctor has told you. If you are not sure, consult your doctor or pharmacist.

Using the medicine

• Vagifem can be started on any day.
• The vaginal tablet should be inserted into the vagina using the applicator.

The "INSTRUCTIONS FOR USE" at the end of this leaflet contain detailed instructions. Read the instructions carefully before using Vagifem.

What dose to use

• For the first 2 weeks, use one vaginal tablet once a day.
• Then, use one vaginal tablet twice a week. Leave a gap of 3-4 days between doses.

General information about treating menopausal symptoms

• Your doctor will determine the lowest effective dose of Vagifem for the shortest possible period. Discuss with your doctor if the recommended dose seems too high or too low.
• Treatment should only be continued if the benefits outweigh the risks. Discuss this with your doctor.

Using a higher dose of Vagifem than recommended

• If you take more Vagifem than recommended, contact your doctor or pharmacist.
• Vagifem is intended for local use in the vagina. The dose of estradiol is so small that you would need to use a large number of tablets to achieve the dose usually used for oral treatment.

Missing a dose of Vagifem

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

Stopping Vagifem

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

If surgery is planned

If the patient is scheduled for surgery, they should inform the surgeon that they are using Vagifem.
It may be necessary to stop using Vagifem 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2, "Blood clots in the veins (venous thromboembolism)"). Before resuming Vagifem, consult your doctor.
If you have any further doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Vagifem can cause side effects, although not everybody gets them.
The following diseases are reported more frequently in women using HRT medications that circulate in the blood than in women not using HRT. This risk is less likely to apply to vaginal products like Vagifem:

• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• stroke;
• likely memory loss, if HRT is started at an age over 65. For more information, see section 2, "Important information before using Vagifem".

Common: may affect up to 1 in 10 women

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

Uncommon: may affect up to 1 in 100 women

• vaginal yeast infections,
• feeling unwell (nausea),
• rash,
• weight gain,
• hot flashes,
• high blood pressure.

Frequency not known (cannot be estimated from the available data)

• diarrhea,
• fluid retention,
• worsening of migraine,
• generalized hypersensitivity (e.g., anaphylactic reaction/anaphylactic shock),
• sleep problems,
• vulvar and vaginal itching,
• itching,
• hives,
• allergic reaction at the application site, such as vaginal rash,
• injury related to the use of the applicator,
• lack of effect of the medicine,
• breast cancer,
• endometrial cancer,
• deep vein thrombosis,
• endometrial hyperplasia,
• vulvar and vaginal pain,
• reaction at the application site.

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

• gallstones,
• various skin disorders:
• skin discoloration, especially on the face or neck, known as pregnancy spots (chloasma);
• painful red skin lumps (erythema nodosum);
• rash with characteristic redness or pain (erythema multiforme).

Reporting side effects
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the "national reporting system" listed in Annex V.
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vagifem

Keep the medicine out of the sight and reach of children.
Do not store in the refrigerator.
Do not use this medicine after the expiry date stated on the carton and blister pack after "EXP". The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.
This medicine may pose a risk to the aquatic environment.

6. Contents of the pack and other information

What Vagifem contains

• The active substance of Vagifem is estradiol 10 micrograms (as estradiol hemihydrate). Each vaginal tablet contains 10 micrograms of estradiol (as estradiol hemihydrate).
• Vagifem also contains: hypromellose, lactose monohydrate, cornstarch, and magnesium stearate.
• The ingredients of the tablet coating are: hypromellose and macrogol 6000.

What Vagifem looks like and contents of the pack

Each white vaginal tablet is placed in a single-use applicator.
The Vagifem tablet has the marking NOVO 278 on one side.
Pack sizes:
18 vaginal tablets with applicators.
24 vaginal tablets with applicators.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd
Denmark
Phone: +45 4444 8888
Date of last revision of the leaflet:12/2024

Other sources of information

Detailed information about this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products http://www.urpl.gov.pl .

INSTRUCTIONS FOR USE

How to use Vagifem

• 1. Open a single blister pack from the side shown in the picture.

• 2. Carefully insert the applicator into the vagina until you feel resistance (8-10 cm).

• 3. To release the tablet, gently press the plunger until you hear a click. The tablet will adhere to the vaginal wall immediately. The tablet will not fall out when standing or walking.

• 4. Remove the applicator and discard it in the trash.