Vagifem

Package leaflet: Information for the user

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Vagifem
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 further questions, please 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 symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4, "Possible side effects".

Contents of the leaflet

1. What Vagifem is and what it is used for
2. What you need to know 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 the active substance 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 a woman's ovaries.

Vagifem belongs to a group of medicines called local estrogen replacement therapy administered vaginally.
It 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.
Vagifem 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.
Experience with treatment in women over 65 years of age is limited.

2. Important information before using Vagifem

Medical history and regular check-ups
Hormone replacement therapy (HRT) carries risks that should be considered when deciding whether to start or continue HRT.
Experience in treating women with 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 an examination, such as a breast and/or gynecological examination, if necessary.
If you start using Vagifem, 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 Vagifem treatment.
Women should undergo regular breast screening as recommended by their doctor.

When not to use Vagifem
If any of the conditions listed below occur or you have any doubts related to them, you should speak with your doctor before starting Vagifem.
Do not use Vagifem if you:

• are allergic (hypersensitive) to estradiol or any of the other ingredients of Vagifem (listed in section 6, “Contents of the pack and other information”);
• 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 uterus);
• have unexplained vaginal bleeding;
• have excessive thickening of the lining of the uterus (endometrial hyperplasia) that has not been treated;
• have had or currently have 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 a disease caused by blood clots in the arteries, e.g., myocardial infarction, stroke, or angina pectoris;
• have been diagnosed with or have had liver disease and liver function tests have not returned to normal;
• have a rare inherited blood disorder called porphyria. If any of the above conditions occur for the first time during treatment with Vagifem, 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 Vagifem. In such cases, your doctor may recommend more frequent monitoring.

• asthma;
• epilepsy;
• diabetes;
• gallstones;
• high blood pressure;
• migraine or severe headaches;
• liver disease, e.g., benign liver tumor;
• endometriosis (presence of uterine lining tissue outside the uterus) or past history of excessive thickening of the uterine lining (endometrial hyperplasia);
• otosclerosis, a disease affecting the eardrum and hearing;
• systemic lupus erythematosus, an autoimmune disease affecting multiple organs;
• increased risk of estrogen-dependent tumors (e.g., breast cancer in 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 heart or kidney dysfunction;
• hereditary or acquired angioedema.

Stop using Vagifem and contact your doctor immediately if any of the following occur during HRT:

• migraine headache occurring for the first time;
• yellowing of the skin or eyes (jaundice), which may be symptoms of liver disease;
• swelling of the face, tongue, and/or throat, difficulty swallowing, or hives together with breathing difficulties, which may indicate angioedema;
• significant increase in blood pressure (symptoms include headache, fatigue, and dizziness);
• any of the conditions listed under “When not to use Vagifem” above;
• if you become pregnant;
• if you experience 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 the veins (venous thromboembolism)”.

Note: Vagifem 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 needed. Please consult your doctor.

HRT and cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Long-term use of oral HRT containing only estrogens may increase the risk of developing endometrial cancer.
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 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 below apply to systemic HRT medicines that circulate in the blood. Vagifem, however, is intended for local vaginal use and is absorbed into the bloodstream only to a very small extent. Worsening or recurrence of the conditions mentioned below during Vagifem use is less likely, but if you have any concerns, you should contact 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.

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

• skin dimpling,
• 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. 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 2,000 women over a 5-year period. Among women who have used HRT for 5 years, it occurs in about 3 out of 2,000 women (i.e., about 1 additional case).

Effects of HRT on the heart and circulation

Blood clots in the veins (venous thromboembolism)
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 use.
Blood clots can have serious consequences and, if they travel to the lungs, 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 prolonged periods 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 a history of thromboembolic disorders requiring long-term anticoagulant therapy;
• 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
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 1,000 women.
Among women aged 50 to 59 using estrogen-only HRT for more than 5 years, the number of cases is 5 to 8 per 1,000 women (i.e., 1 additional case).

Heart disease (heart attack)
Women using estrogen-only HRT do not have an increased risk of 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 due to HRT use 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 8 per 1,000 women on average. Among women aged 50 to 59 using HRT, the number of cases over 5 years is 11 per 1,000 women (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 age 65. Please 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 obtained without a prescription, herbal remedies, or other natural products. The likelihood of interactions with other medicines is low because Vagifem is applied locally into the vagina. However, Vagifem may affect other local vaginal treatments.

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

Driving and operating machinery
It is not known whether Vagifem affects the ability to drive or operate machinery.

3. How to use Vagifem

Always use this medicine exactly as your doctor has instructed. If in doubt, consult your doctor or pharmacist.
How to use the medicine

• Vagifem treatment 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 provide detailed guidance. Read the instructions carefully before using Vagifem.
What dose to use

• For the first 2 weeks, use one vaginal tablet once daily.
• After that, use one vaginal tablet twice a week. Leave an interval of 3 to 4 days between doses.

General information on the treatment of menopausal symptoms

• Your doctor will prescribe the lowest effective dose of Vagifem for the shortest possible duration necessary to treat your symptoms. Talk to your doctor if the prescribed dose seems too high or too low.
• Treatment should continue only if the benefits clearly outweigh the risks. Discuss this with your doctor.

If you use more Vagifem than you should

• If you use more Vagifem than recommended, contact your doctor or pharmacist.
• Vagifem 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 with oral therapy.

If you miss 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 a forgotten dose.

Stopping Vagifem treatment
Do not stop treatment with 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 you are scheduled for surgery, inform your surgeon that you 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 veins (venous thrombosis)”).
Consult your doctor before restarting Vagifem after surgery.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
The conditions listed below are reported more frequently in women using systemic hormone replacement therapy (HRT) medicines circulating in the bloodstream than in women who do not use HRT. This risk is lower with medicines administered vaginally, such as Vagifem:

• ovarian cancer;
• blood clots in the legs or lungs (venous thromboembolic disease);
• stroke;
• possible memory loss if HRT is initiated after the age of 65. For further information, see section 2, "Important information before using Vagifem".

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.

Frequency not known (cannot be estimated from available data)

• diarrhoea,
• fluid retention,
• worsening of migraine,
• generalized hypersensitivity (e.g. anaphylactic reaction/anaphylactic shock),
• sleep disorders,
• vaginal and genital pruritus,
• pruritus,
• urticaria,
• local hypersensitivity reaction at site of application, such as genital rash,
• injury related to applicator use,
• lack of therapeutic effect,
• breast cancer,
• endometrial cancer,
• deep vein thrombosis,
• endometrial hyperplasia,
• vulvar and vaginal pain,
• local reaction at site of application.

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

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

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Drug Reactions, 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.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Vagifem

Keep this 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 packaging. The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. 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 Vagifem contains

• The active substance is estradiol 10 micrograms (in the form of estradiol hemihydrate). Each vaginal tablet contains 10 micrograms of estradiol (as estradiol hemihydrate).
• Other components are: hypromellose, monohydrate lactose, maize starch and magnesium stearate.
• Components of the tablet coating: 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 is marked with the imprint NOVO 278 on one side.
Pack sizes:
18 vaginal tablets with applicators.
24 vaginal tablets with applicators.
For more detailed information, please contact the responsible entity or the parallel importer.
Marketing Authorisation Holder in Spain, country of export:
Isdin S.A.
Provençals 33
08019 Barcelona
Spain
Manufacturer:
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd
Denmark
Parallel importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Marketing Authorisation number in Spain, country of export: 665149.0
Parallel import authorisation number: 247/25

INSTRUCTIONS FOR USE
How to use Vagifem

1. Open the individual blister pack from the side shown in the picture.

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

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

4. Remove the applicator and dispose of it in the trash.