PROSPECTO : INFORMATION FOR THE USER

Blissel50 micrograms/g vaginal gel

Estriol

Read this prospect carefully before starting to use this medicationbecause it contains important information for you

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribedonlyto you and should not be given to other people, even if they have the same symptomsas you, as it may harm them.
• Ifyou experienceadverse effectsconsultyour doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Blissel belongs to a group of medications called vaginal local hormone replacement therapy (HRT).

It is used to relieve symptoms of vaginal menopause, such as dryness or irritation. In medical terms, this is known as «vaginal atrophy». This is caused by a decrease in estrogen levels in the body and occurs naturally after menopause.

Blissel acts by restoring the estrogen produced normally in the ovaries. It is inserted into the vagina, so that the hormone is released only where it is needed, and in this way, it can relieve vaginal discomfort.

Medical History and Check-Ups

The use of hormone replacement therapy carries risks that must be considered if you decide to start or continue treatment.

Before starting (or restarting) hormone replacement therapy, your doctor will ask about your medical history and that of your family. Your doctor may decide to perform a physical examination, which may include a breast examination and/or an internal examination, if necessary.

Once you have started takingBlissel, you should visit 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 withBlissel.

Get regular mammograms, as recommended by your doctor.

Do Not Use Blissel

If you are affected by any of the following situations or have doubts about any of them, consult your doctor before using Blissel:

• If you have, have had, or suspect you may have breast cancer
• If you have or suspect you may have cancer that is sensitive to estrogen, such as endometrial cancer (the lining of the uterus)
• If you have unexplained vaginal bleeding
• If you have abnormal growth of the endometrium (endometrial hyperplasia) that is not being treated
• If you have or have had blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism)
• If you have a blood clotting disorder (such as deficiency of protein C, protein S, or antithrombin)
• If you have or have had diseases caused by blood clots in the arteries, such as a stroke, angina, or heart attack
• If you have or have had an acute liver disease and your liver function tests have not normalized
• If you have porphyria (a rare genetic metabolic disorder)
• If you areallergic(hypersensitive) to estriol or any of the other components ofBlissel(including those listed in section 6 "Additional Information").

If any of the above conditions appear for the first time while taking Blissel, stop taking it immediately and consult your doctor immediately.

Warnings and Precautions

This medication is administered by inserting an applicator into the vagina. This may cause discomfort or pain in women with severe vaginal atrophy (narrowing or inflammation of the vaginal walls).

Please inform your doctor if you have or have had any of the following diseases/conditions, which may rarely recur or worsen during treatment with Blissel. If so, you should visit your doctor more frequently for medical check-ups:

• Very high levels of fat in the blood (triglycerides)
• Abnormal growth of the tissue that covers the inside of the uterus outside of it (endometriosis) or a history of excessive growth of the tissue that covers the uterus (endometrial hyperplasia)
• Fibroids inside the uterus
• High blood pressure
• Diabetes
• Stones in the gallbladder
• Migraine or severe headache
• A rare immune disease called systemic lupus erythematosus (SLE)
• Epilepsy (seizures)
• Asthma
• A disease that affects the eardrum and hearing (otosclerosis)
• Fluid retention due to heart or kidney problems
• Increased risk of developing blood clots (see "Blood clots in a vein (thrombosis))
• Increased risk of developing estrogen-sensitive cancer (e.g., if your mother, sister, or grandmother has had breast cancer)
• Liver disease, such as a benign liver tumor
• Hereditary and acquired angioedema

Reasons to Visit Your Doctor Immediately

• Jaundice (yellowing of the whites of the eyes and skin) or liver problems
• Sudden increase in blood pressure
• Migraine or severe headache for the first time
• Pregnancy
• If you experience any of thecircumstancesdescribed in the section "Do Not Use Blissel".
• If you experience signs of having a blood clot, such as:

• Painful and swollen legs
• Sudden chest pain
• Difficulty breathing.

For more information, see "Blood clots in a vein (thrombosis)".

If any of the above situations occur, your doctor may need to interrupt treatment and offer you an alternative.

Note: Blissel is not a contraceptive. If you have had less than 12 months since your last menstrual period or if you are under 50 years old, you may need to use additional contraceptive methods to avoid pregnancy. Consult your doctor for advice.

Hormone Replacement Therapy and Cancer

Endometrial Hyperplasia and Uterine Cancer

Taking estrogen-only hormone replacement therapy for a prolonged period may increase the risk of developing endometrial cancer (the lining of the uterus).

It is not clear if there is a similar risk with Blissel when used for repeated or long-term treatments (over one year). However, it has been shown that the absorption of Blissel into the bloodstream is very low; therefore, the addition of a progestin is not necessary.

If you bleed or spot, it is usually nothing to worry about, but you should schedule an appointment to see your doctor. It could be a sign that the endometrium has become thicker.

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

Treatment with medications containing higher doses of estrogen that can elevate estrogen levels in the bloodstream (such as pills or patches) increases the risk of abnormal growth of the endometrium (endometrial hyperplasia), certain types of cancer such as breast cancer and endometrial cancer, and blood clots in the veins.

Breast Cancer

The available data indicate that using Blissel does not increase the risk of breast cancer in women who have not had breast cancer in the past. It is not known if Blissel can be used safely in women who have had breast cancer in the past.

Check Your Breasts Regularly

Get regular mammograms, as recommended by your doctor.

Ovarian Cancer

Ovarian cancer is rare: much rarer than breast cancer. The use of estrogen-only HRT has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who are not taking HRT, approximately 2 women out of every 2000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be around 3 cases per 2000 users (i.e., about 1 additional case).

Effect of Hormone Replacement Therapy on the Heart and Circulation

Blood Clots in a Vein

The risk ofblood clots in the veinsis approximately 1.3 to 3 times higher in women using hormone replacement therapy than in those who do not use it, especially during the first year of treatment.

Blood clots can be serious, and if one breaks loose and travels to the lungs, it can cause chest pain, shortness of breath, fainting, or even death.

The likelihood of havinga blood clot in the veinsincreases with age and if you have any of the following conditions. Inform your doctor if you have any of these conditions:

• You are unable to walk for a long period due to a major surgery, injury, or illness,
• You have significant obesity (BMI>30 kg/m2),
• You have a blood clotting disorder that requires prolonged treatment with a medication to prevent blood clots,
• You have a family member who has had a blood clot in the leg, lung, or other organ,
• You have systemic lupus erythematosus (SLE),
• You have cancer.

Comparison

An average of 4 to 7 out of every 1,000 women in the 50-year age group who are not on hormone replacement therapy may have a blood clot in a vein over a 5-year period. In women in the 50-year age group who have been on hormone replacement therapy with estrogen only for more than 5 years, there will be 5 to 8 cases per 1,000 users (i.e., 1 additional case).

Cardiovascular Disease (Myocardial Infarction)

Women taking only estrogen do not have an increased risk of developing cardiovascular disease.

Stroke

The risk of stroke is approximately 1.5 times higher in women using hormone replacement therapy than in those who do not use it. The number of additional stroke cases due to hormone replacement therapy increases with age.

Comparison

An average of 8 out of every 1,000 women in the 50-year age group who are not on hormone replacement therapy may have a stroke over a 5-year period. In women in the same age group on hormone replacement therapy for more than 5 years, there will be 11 cases per 1,000 users (i.e., 3 additional cases).

Using Blissel with Other Medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including over-the-counter medications, herbal remedies, or other natural products.

As Blissel contains a very low dose of estriol and is for local treatment, it is not expected to affect or be affected by the use of other medications. However, interactions with other locally applied vaginal treatments should be considered.

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

You should not use Blissel if you are pregnant.

If you become pregnant while taking Blissel, inform your doctor immediately and do not use Blissel.

You should not use Blissel during breastfeeding.

Driving and Using Machines

Blissel does not affect your ability todrive and use machines.

Blissel Contains

Parahydroxybenzoic acid methyl ester, sodium salt (E 219) and parahydroxybenzoic acid propyl ester, sodium salt (E 217).

Do not use this medication if you are allergic to any of its components.

Follow exactly the administration instructions for Blissel indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose for the first three weeks of treatment is one application per day, preferably before going to bed.After 3 weeks of use, your discomfort should have decreased and the dose should be reduced. You may only need one application twice a week.

Use the applicator to introduce the gel into the vagina (recommended before going to bed).

Your doctor will try to prescribe the lowest dose to treat your symptom for as long as necessary. Consult your doctor if you think this dose is too strong or not strong enough.

The following instructions explain how to use the gel.

You can see all the components of the tube and the applicator in the following drawing, which is formed by the cannula and the plunger.

1. Unscrew the cap from the tube,inversion the cap and use the pointed tip to break the seal on the tube's neck. Do not use if the seal is broken.

2. Remove a cannula and the plunger. Insert the white plunger along the cannula. Screw the cannula into the end of the tube.

3.Tightenthe tube to fill the applicator with the gel up to the fill mark. The applicator will stop at the mark.

4. Unscrew the cannula from the tube and put the cap back on the tube.

5. To apply the gel, lie down, insert the end of the applicator deeply into the vagina and push the plunger slowly downwards.

6. Afteruse

• Tube of 10g – 1 Blister with 10 disposable cannulas and 1 reusable plunger
• Tube of 30g – 3 Blisters with 30 disposable cannulas and 1 reusable plunger

Remove the plunger from the cannula, discard the cannula and clean the plunger thoroughly with clean and warm water to be able to use it again for the next application.

• Tube of 10g – 1 Bag with 1 reusable cannula and 1 reusable plunger
• Tube of 30g – 1 Bag with 1 reusable cannula and 1 reusable plunger

Remove the plunger from the cannula and clean the cannula and plunger thoroughly with clean and warm water to be able to use them again for the next application.

If you use more Blissel than you should

If too much gel is applied or someone has accidentally ingested some gel, do not worry.

You may feel unwell and some women may experience vaginal bleeding a few days later.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to useBlissel

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

Apply the missed dose as soon as you remember, unlessmore than 12 hourshave passed. In this case, simply skip the missed dose.

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

Like any other medication, this medication may cause side effects, although not everyone will experience them.

Inform your doctor immediatelyif any of the circumstances described in the section “What you need to know before starting to use Blissel” occur, such as vaginal bleeding.Your doctor may need to interrupt treatment and offer an alternative.

At the beginning of treatment, irritation or itching in the vagina may occur. In most people, these side effects disappear with continued use.Inform your doctor if vaginal bleeding occurs or if any of the following side effects worsen or continue.

Frequent side effects (may affect up to 1 in 10 people):

• Itching, irritation inside or around the vagina.

Rare side effects (may affect up to 1 in 100 people):

• Lower abdominal pain,
• Skin irritation,
• Vaginal rash,
• Headache,
• Candidiasis (vaginal infection).

The following diseases are reported more frequently in women using blood-circulating THS medications compared to women not using THS. These risks occur less frequently in treatments administered vaginally, such as Blissel

• Clots in the veins of the legs or lungs (venous thromboembolism).
• Ovarian cancer.
• Stroke.
• Probable memory loss if THS is started after the age of 65.

For more information about these side effects, see Section 2.

The following side effects have been reported associated with other hormone replacement therapies.

• Diseases of the gallbladder,
• Diverse skin disorders:

- Skin pigmentation, especiallyon the face or neck, known as “pregnancy spots” (melasma),

-Painful and reddish nodules on the skin (erythema nodosum),

- Skin rash with lesions or papules in the shape of a target (erythema multiforme).

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

Keep out of sight and reach of children. Do not use this medication after the expiration date that appears on thecontainer.

The expiration date is the last day of the month indicated.

Store below 25ºC.

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

Composition ofBlissel

The active principle is estriol.

The filled applicator up to the mark corresponds to a dose of 1 g of vaginal gel. Each gram of gel contains 50 micrograms of estriol.

The other components are::Glycerol (E 422), methyl parahydroxybenzoate, sodium salt (E 219), propyl parahydroxybenzoate, sodium salt (E 217), polycarbophil, carbopol, sodium hydroxide, hydrochloric acid, purified water.

Appearance of Blissel and contents of the package

This medication is an incolor, transparent or slightly translucent vaginal gel, which contains an aluminum tube of 10g or a tube of 30 g.

• 10g Presentation - Blister with 10 disposable tubes (cannulas)and a reusable plunger.

Carton box with a 10g tube of Blissel and a blister with 10 disposable tubes (cannulas) marked with a filling mark and a reusable plunger.

• 10g Presentation - Bag with 1 reusable tube (cannula)and a reusable plunger.

Carton box with a 10g tube of Blissel and a bag with 1 reusable tube (cannula) marked with a filling mark and a reusable plunger.

• 30g Presentation - 3 Blister with 10 disposable tubes (cannulas)and a reusable plunger each.

Carton box with a 30g tube of Blissel and three blisters, each with 10 disposable tubes (cannulas) marked with a filling mark and a reusable plunger.

• 30g Presentation - Bag with 1 reusable tube (cannula)and a reusable plunger.

Carton box with a 30g tube of Blissel and a bag with 1 reusable tube (cannula) marked with a filling mark and a reusable plunger.

Only some sizes of packaging may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

ITALFARMACO, S.A.

San Rafael, 3 -28108 Alcobendas (Madrid)

Responsible manufacturer for release:

ITALFARMACO, S.A.

San Rafael, 3 -28108 Alcobendas (Madrid), SPAIN

This medication is authorized in the member states of the European Economic Areawith the following names:

• Spain:Blissel 50 micrograms/g vaginal gel
• Sweden:Blissel 50 mikrogram/g vaginal gel
• France:Blissel 50 microgrammes/g gel vaginal
• Portugal:Blissel 50 microgramas/g gel vaginal
• Greece:Blissel 50 μικρογραμμ?ρια/g κολπικ? γ?λη
• Belgium:Blissel 50 microgrammes/g gel vaginal
• Denmark:Gelisse 50 mikrogram/g vaginalgel
• Finland:Blissel 50 mikrog/g emätingeeli
• Ireland:Blissel 50 micrograms/g vaginal gel
• Netherlands:Blissel 50 microgram/g gel voor vaginaalgebruik
• Norway:Gelisse 50 mikrogram/g vaginalgel
• England:Blissel 50 micrograms/g vaginal gel
• Cyprus:Blissel μικρογραμμ?ρια/g κολπικ? γ?λη
• Poland::Blissel 50 zel pochwowy
• Austria:Blissel 50 Mikrogramm/g Vaginalgel

Date of the last review of this leaflet:March 2022

The detailed and updated information of this medication is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/