Patient Information

Vagifem 10 micrograms vaginal tablets coated

estradiol

Read this leaflet carefully before you start 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 questions, ask your doctor or pharmacist.

·This medicine has been prescribed for you. Do not pass it on to others even if their symptoms are the same as yours.

·If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4, “Possible side effects”).

1. What Vagifem is and what it is used for

2. What you need to know before you start using Vagifem

3. How to use Vagifem

4. Possible side effects

5. Storage of Vagifem

6. Contents of the pack and additional information

Vagifem contains estradiol

· Estradiol is a female sex hormone

· It belongs to the group of hormones called estrogens

· It is exactly the same as the estradiol produced in the ovaries of women

Vagifem belongs to the group of medications called Vaginal Hormone Replacement Therapy (VHRT).

It is usedto relieve vaginal menopausal symptoms such as dryness or irritation. In

medical terms, this is known as “vaginal atrophy”. It is caused by a decrease in

estradiol levels in the body. This occurs naturally with menopause.

Vagifemactsby substituting the estradiol that is normally produced in the ovaries of women. It is

inserted into the interior of your vagina, so that the hormone is released in the place

where it is needed.This may alleviate vaginal discomfort.

The experience in treating women over 65 years of age is limited.

Medical History and Regular Check-ups

The use of THS involves risks that should be considered when deciding whether to start or continue treatment.

The experience in treating women with premature menopause (due to failure or ovarian surgery) is limited. If you have premature menopause, the risks of using TRH may be different.

Before starting (or resuming) the use of THS, your doctor will ask 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 with Vagifem, you should consult your doctor for check-ups at least once a year. In these check-ups, consult your doctor about the benefits and risks of continuing with Vagifem.

Attend regular breast examinations as indicated by your doctor.

Do not use Vagifem:

If you are affected by any of the following cases. If you are unsure about any of the following points, consult your doctor before taking Vagifem.

Do not use Vagifem if:

· you are allergic (hypersensitive) to estradiol or to any of the other components of Vagifem (including those listed in section 6 "Packaging and Contents")

· you have or have had breast cancer, or if you suspect you may have it

· you have or have had cancer dependent on estrogens such as endometrial cancer or if you suspect you may have it

· you have abnormal vaginal bleeding

· you have an excessive growth of cells that cover the uterus (endometrial hyperplasia) that is not being treated

· you have or have had blood clots in the veins (deep vein thrombosis) or in the lungs (pulmonary embolism)

· you have any coagulation disorder (such as deficiency of protein C, protein S or antithrombin)

· you have or have had a disease caused by blood clots in the arteries such as a heart attack, stroke or angina pectoris

· you have or have had liver disease and your liver function tests have not returned to normal

· you have a rare blood disorder called "porphyria" that is inherited (hereditary)

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

Warnings and Precautions

Consult your doctor if you have or have had any of the following problems before starting treatment, as they may return or worsen during treatment with Vagifem. If so, consult your doctor more frequently for medical examinations.

· Asthma

· Epilepsy

· Diabetes

· Gallstones (biliary calculi)

· High blood pressure

· Migraine or severe headaches

· Liver disorders such as benign liver tumors

· Endometriosis or a history of excessive growth of cells that cover the uterus (endometrial hyperplasia)

· A disease that affects the eardrum and ear (otosclerosis)

· A disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)

· High risk of developing cancer dependent on estrogens (such as having a mother, sister or grandmother who has had breast cancer)

· High risk of developing blood clots (see "Blood clots in veins (thrombosis)")

· Fibroids inside the uterus

· High levels of fat in the blood (triglycerides)

· Fluid retention due to heart or kidney problems

• Hereditary and acquired angioedema

Discontinue treatment with Vagifem and visit your doctor immediately

If you experience any of the following situations when using THS:

· Migraine-type headache for the first time

· Yellowing of the skin or in the white of the eyes (jaundice). This may be a symptom of liver disease

• Swelling of the face, tongue and/or throat and/or difficulty swallowing or urticaria, along with difficulty breathing, which are indicative symptoms of angioedema

· A significant increase in your blood pressure (the symptoms may be headache, fatigue and dizziness)

· Any of the situations detailed in the previous section "Do not use Vagifem"

· If you become pregnant

· If you observe 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 veins (thrombosis)"

Note: Vagifem 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 need to continue using additional contraceptive methods to avoid pregnancy. Consult your doctor for advice.

THS and Cancer

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

The prolonged use of THS with estrogens alone may increase the risk of developing endometrial cancer (cancer of the lining of the uterus).

It is not clear if there is a similar risk with Vagifem when used for repeated or long-term treatments (more than one year). However, Vagifem has shown very low absorption in the blood, and therefore, the addition of a progestogen is not necessary.

Do not worry if you experience bleeding or spotting, but consult your doctor.

This may be a sign of endometrial hyperplasia.

The following risks apply to hormone replacement therapy (HRT) that circulates in the blood. However, Vagifem is used for local treatment in the vagina and absorption in the blood is very low. It is less likely that the situations mentioned below will worsen or recur during treatment with Vagifem, but you should see your doctor if you are concerned.

Breast Cancer

The available data indicate that using Vagifem does not increase the risk of breast cancer in women who have not had breast cancer in the past. It is not known if Vagifem 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:

• wrinkles or creases in the skin.

• changes in the nipple.

• any lump that you can see or feel.

Additionally, it is recommended to participate in breast cancer screening programs when offered.

Ovarian Cancer

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

Comparison

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who are not taking HRT, about 2 women per 2,000 will be diagnosed with ovarian cancer over a 5-year period. In women who have been taking 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 taking it.

Blood clots can be serious and if one of them reaches the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.

You are more likely to develop blood clots as you get older and if any of the following cases affect you. Inform your doctor if you experience any of the following situations:

· you are unable to walk for a long time due to major surgery, injury or illness (see also section 3, if you are to undergo surgery)

· if you have significant obesity (BMI >30 kg/m2)

· if you have a coagulation disorder that requires long-term treatment with a medication to prevent blood clots

· if a close relative has ever had a blood clot in the legs, lungs, or other organs

· you have lupus erythematosus (LES)

· you have cancer

In case of signs of blood clots, see "Discontinue treatment with Vagifem and visit your doctor immediately"

Comparison

In women aged 50-54 who are not taking HRT, it is expected that a mean of 4 to 7 out of every 1,000 will have a blood clot in a vein over a 5-year period.

In women aged 50-54 who have been taking HRT 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 taking HRT with estrogens only, 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 cases of stroke due to HRT increases with age.

Comparison

In women aged 50-54 who are not taking HRT, a mean of 8 out of every 1,000 will suffer a stroke over a 5-year period.

In women aged 50-54 who take HRT, there will be 11 cases per 1,000 users over a 5-year period (i.e., 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 some type of HRT after the age of 65. Consult your doctor.

Use of Vagifem with Other Medications

Inform your doctor or pharmacist if you are using or have used recently other medications, including those acquired without a prescription, those made from herbal plants or other natural products. However, Vagifem is used for local treatment in the vagina and is unlikely to affect other medications. Vagifem may affect other treatments applied vaginally.

Fertility, Pregnancy and Breastfeeding

Vagifem is for use in postmenopausal women. If you become pregnant, discontinue use of Vagifem and contact your doctor immediately.

Driving and Operating Machinery

Unknown.

Follow exactly the medication administration instructions indicated by your doctor.

Consult your doctor or pharmacist if you have any doubts.

Medication use

· You can start using Vagifem on any day that suits you best

· Insert the vaginal tablet into your vagina using the applicator

In the "USE INSTRUCTIONS" section at the end of this prospectus, you will be indicated how

to do it. Read the instructions carefully before using Vagifem.

Frequency of use

· Apply one vaginal tablet daily for the first two weeks

· Subsequently, apply one vaginal tablet twice a week. There should be a gap of 3 or 4 days between each application.

General information on the treatment of menopause symptoms

.

· Your doctor will have to prescribe the lowest dose of Vagifem to treat your symptom 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 is greater than the risk. Consult your doctor about this.

If you use more Vagifem than you should

· If you have used more Vagifem than you should, consult your doctor or pharmacist

· Vagifem is used for local treatment inside the vagina. The dose of estradiol is so low that a considerable number of tablets would be needed to achieve the normally used oral dose.

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

If you forget to use Vagifem

· If you forget a dose, use the medication as soon as you remember

· Do not use a double dose to compensate for the missed doses.

If you interrupt treatment with Vagifem

Do not interrupt treatment with Vagifem without consulting your doctor. Your doctor will explain the effects of interrupting treatment to you. They will discuss other treatment options with you.

If you need to undergo surgery

If you are to undergo a surgical procedure, inform the surgeon that you are taking Vagifem. You may need to stop taking Vagifem for 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 taking Vagifem again.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

However, the following diseases are observed more frequently in women using systemic THS medications that circulate in the blood, compared to women who do not use THS. These risks are less related to vaginal treatments, such as Vagifem:

• ovarian cancer;

• blood clots in the veins of the legs or lungs (venous thromboembolism);

• stroke;

• probable loss of memory if THS is started at an age of 65 years or older;

For more information on these side effects, see section 2, “What you need to know before starting to use Vagifem”.

Frequent: may affect up to 1 in 10 people

· Headache

· Stomach pain

· Vaginal bleeding, discharge or discomfort

Rare: may affect up to 1 in 100 people

· Genital fungal infection

· Dizziness (nausea)

· Skin rash

· Weight gain

· Hot flashes

· Hypertension

Very rare: may affect up to 1 in 10,000 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

· Different skin alterations

- skin discoloration, especially on the face or neck, known as

“pregnancy mask” (melasma)

- painful, reddish nodules on the skin (erythema nodosum)

- skin eruptions with red inflammation or sores (erythema multiforme).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist or nurse, even if it is a possible side effect that does not appear in this prospectus.

You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not refrigerate.

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

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and the medication that you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and the medication that you no longer need. By doing so, you will help protect the environment.

Composition of Vagifem

The active ingredient is estradiol 10 micrograms (as estradiol hemihydrate). Each vaginal tablet

contains 10 micrograms of estradiol (as estradiol hemihydrate).

The other components are: hypromellose, lactose monohydrate, cornstarch, and magnesium stearate.

The coating contains: hypromellose and macrogol 6000.

Appearance of the product and contents of the packaging

Each white vaginal tablet comes in a single-use applicator.

Vagifem is marked with NOVO 278 on one of the faces.

Package sizes:

18 vaginal tablets with applicator

24 vaginal tablets with applicator

All package sizes may not be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder:

Isdin S.A.

Provençals 33

08019 Barcelona

Spain

Manufacturer responsible:

Novo Nordisk A/S

Novo Allé

2880 Bagsvaerd

Denmark

Last review date of this leaflet:july 2022

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)

http://www.aemps.gob.es/

USAGE INSTRUCTIONS

How to use Vagifem

1. Separate an individual blister from the packaging.

Open it at the end as indicated in the drawing

2. Insert the applicator carefully into the vagina.

Stop when you feel some resistance (8-10 cm).

3. To release the tablet, press the trigger gently until you hear a "click".

The tablet is immediately fixed to the vaginal wall.

The tablet will not fall off even if you stand up or walk.

4. Remove the applicator and dispose of it.