Vagifem

Package leaflet: Information for the user

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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4, ‘Possible side effects’.

What this leaflet contains:

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 estradiol:

• Estradiol is a female sex hormone.
• It belongs to a group of hormones called estrogens.
• It is exactly the same as the estradiol produced by the ovaries.

Vagifem belongs to a group of medicines used for vaginal Hormone Replacement Therapy (HRT).
It is used to relieve symptoms of vaginal irritation or dryness. Medically, this is known as "atrophic
vaginitis". It is caused by a decrease in estrogen levels in the body. This occurs naturally after
menopause.
Vagifem works by replacing the estrogen normally produced by the ovaries. It is inserted into the vagina so that
the hormone is released where needed. This will relieve vaginal discomfort.
Experience in women over 65 years of age is limited.

2. What you should know before using Vagifem

Medical history and regular medical check-ups
Hormone replacement therapy (HRT) carries certain risks that should be considered when deciding whether to start or continue treatment.
Experience in treating women with premature menopause (due to ovarian failure or surgical treatment) is limited. If you have premature menopause, the risks associated with using HRT may differ. Please speak 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 a gynecological examination, if necessary.
Once you have started treatment with Vagifem, you should see your doctor for regular check-ups at least once a year. During these check-ups, discuss with your doctor the benefits and risks of continuing treatment with Vagifem.
Perform regular breast monitoring as recommended by your doctor.

Do not use Vagifem:
If any of the following apply to you. If you are unsure about any of the points listed below, speak with your doctor before using 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’).
• You have or have had breast cancer or there is suspicion of it.
• You have or have had or there is suspicion of an estrogen-dependent tumor, such as cancer of the uterine lining (endometrium).
• You have unexplained vaginal bleeding.
• You have untreated excessive growth of the uterine lining (endometrial hyperplasia).
• You have or have had blood clots in the veins of the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• You have blood clotting disorders (thrombophilic disorders such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• You have a blood clotting disorder (thrombophilic disorders, such as deficiency of protein C, protein S, or antithrombin).
• You have or have recently had a condition caused by blood clots in the arteries, such as heart attack, stroke, or angina.
• You have or have had a liver disorder and your liver function tests have not returned to normal.
• You have a rare inherited blood disorder called “porphyria”.

If any of the above conditions occur while you are using Vagifem, stop taking it immediately and consult your doctor.

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

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

Stop using Vagifem and contact your doctor immediately if you notice any of the following while using HRT:

• A new type of migraine headache you have never had before
• Yellowing of the skin or eyes (jaundice). These could be signs of a liver disorder
• Swelling of the face, tongue, and/or throat, and/or difficulty swallowing, or hives, associated with breathing difficulties, which may indicate angioedema
• Significant increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• Any of the conditions listed in the section “Do not use Vagifem”
• If you become pregnant
• If you notice signs of blood clots such as:
  • swelling, pain, or redness in the legs
  • sudden chest pain
  • difficulty breathing. For more information, see “Blood clots in a vein (thrombosis)”.

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, you still need to use additional contraception to prevent pregnancy. Please consult your doctor for advice.

HRT and tumors

Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial cancer)
Long-term treatment with estrogen-only HRT may increase the risk of developing tumors of the uterine lining (endometrium).
It is not certain whether there is a similar risk with Vagifem when used repeatedly or for prolonged periods (more than one year). However, Vagifem 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, it 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 apply to systemic hormone replacement therapy (HRT) that circulates in the blood. However, Vagifem is used for local vaginal treatment and has very low systemic absorption. It is therefore less likely that the conditions listed below will worsen or reappear during treatment with Vagifem, but you should speak with your doctor if you are concerned.

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

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 HRT 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 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 the 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, especially during the first year of treatment.
Blood clots are not always serious, but if a clot travels to the lungs, it can cause chest pain, shortness of breath, collapse, or even death.

Your risk of developing blood clots in blood vessels is higher if any of the following apply to you. Inform your doctor if:

• You cannot walk or must remain immobile for long periods due to surgery, trauma, or illness (see also section 3, ‘If you are going to have surgery’)
• You are significantly overweight (BMI > 30 kg/m²)
• You have a clotting disorder requiring long-term treatment with anticoagulant medication
• You or a close relative have previously had a blood clot in the leg, lung, or another organ
• You have systemic lupus erythematosus (SLE)
• You have a tumor

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

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

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

Stroke
The risk of stroke is about 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 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 who take HRT for more than 5 years, 11 cases per 1,000 users are diagnosed (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 any type of HRT after age 65. Please speak with your doctor.

Other medicines and Vagifem
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines, herbal remedies, or other natural products. However, Vagifem is used for local vaginal treatment and does not affect the use of other systemic medications. Vagifem may affect other treatments applied vaginally.

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

Driving and using machines
No known effects.

3. How to use Vagifem

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

How to use this medicine

• You may start treatment with Vagifem on any day that is convenient for you.
• Insert the vaginal tablet into the vagina using the applicator.

The 'USER INSTRUCTIONS' at the end of this leaflet will show you how to do this. Read the instructions carefully before using Vagifem.

Dosage

• Use one vaginal tablet every day for the first 2 weeks.
• Then use one vaginal tablet twice a week. Leave an interval of 3 or 4 days between each dose.

General information on the treatment of menopausal symptoms

• When using medicines to treat menopausal symptoms, it is recommended to use the lowest effective dose for the shortest duration possible.
• Your doctor will aim to prescribe the lowest dose of Vagifem needed to treat your symptoms and for the shortest time necessary. Talk to your doctor if you think this dose is too high or not strong enough.
• Treatment should continue only if the benefits outweigh the risks. Discuss this with your doctor.

If you use more Vagifem than you should

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

If you forget to use Vagifem

• If you forget a dose, use the medicine as soon as you remember.
• Do not use a double dose to make up for the forgotten dose.

If you stop using Vagifem

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

If you are going to have surgery

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 avoid the risk of blood clots (see section 2, Blood clots in a blood vessel). Ask your doctor when you can start using Vagifem again.

If you have any questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following conditions have been reported more frequently in women receiving systemic TOS therapy (which circulates in the bloodstream) compared to women not using TOS. These risks are lower with vaginal treatments such as Vagifem:

• ovarian carcinoma;
• blood clots in blood vessels of the legs or lungs (venous thromboembolism);
• heart disorders;
• stroke;
• possible memory loss in women who start any type of TOS after the age of 65. For further information on these side effects, see section 2, "What you should know before using Vagifem".

Common: may affect more than 1 in 10 people

• Headache
• Stomach discomfort
• Vaginal bleeding, spotting, and irritation.

Uncommon: may affect more than 1 in 100 people

• Fungal genital infections
• Malaise (nausea)
• Rash
• Weight gain
• Hot flushes
• Hypertension.

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

• Diarrhea
• Fluid retention
• Worsening of migraine
• Generalized hypersensitivity (e.g., anaphylactic reactions/shock).

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

• Cholelithiasis (gallstones)
• Various skin changes:
  • 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 effects, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the national reporting system at 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 Vagifem

Keep this medicine out of the sight and reach of children.
Do not freeze.
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 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. This will help protect the environment.
This medicine may pose a risk to the aquatic environment.

6. Package contents and other information

What Vagifem contains

• The active substance 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, maize starch and magnesium stearate.
• The coating film contains: hypromellose and macrogol 6000.

Description of the appearance of Vagifem and package contents
Each white vaginal tablet is placed in a single-use applicator.
Vagifem is engraved on one side with the code NOVO 278.
Pack sizes:
18 vaginal tablets with applicators.
24 vaginal tablets with applicators.
Not all pack sizes may be marketed.

MARKETING AUTHORISATION HOLDER AND MANUFACTURER
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd
Denmark

Other sources of information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco).

USER INSTRUCTIONS
How to use Vagifem

1. Remove a single blister pack from the packaging. Open it at the end as shown in the image.

2. Carefully insert the applicator into the vagina. Stop when you meet resistance (8–10 cm).

3. To release the tablet, gently press the button until you hear a click. The tablet is then immediately deposited against the vaginal wall.

It will not fall out when standing or walking.

4. Remove the applicator and dispose of it.

© 2017
Novo Nordisk A/S