PROSPECTO : INFORMATION FOR THE USER

Gelistrol50 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 effectsconsult your doctor or pharmacist, even if they are not listed in this prospect.See section 4.

Gelistrol belongs to a group of medications called local vaginal 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.

Gelistrol acts by restoring the estrogen that is normally produced 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 should be considered when starting or continuing 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 takingGelistrol, 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 withGelistrol.

Have regular mammograms as recommended by your doctor.

Do Not Use Gelistrol

• Do not use Gelistrol if you are affected by any of the following situations or have doubts about any of them, consult your doctor before using Gelistrol:suffer from, have suffered, or suspect you may suffer from breast cancer,
• if you suffer or suspect you may suffer from estrogen-sensitive cancer, such as endometrial cancer (endometrium lining),
• if you experience unexplained vaginal bleeding,
• if you suffer from abnormal growth of the endometrium (endometrial hyperplasia) that is not being treated,
• if you suffer or have suffered from blood clots in the veins of the legs (deep vein thrombosis) or in the lungs (pulmonary embolism),
• if you have a blood clotting disorder (such as protein C deficiency, protein S deficiency, or antithrombin deficiency),
• if you suffer or have suffered from arterial diseases caused by blood clots, such as a stroke, angina, or heart attack,
• if you suffer or have suffered from acute liver disease and your liver function tests have not normalized,
• if you suffer from porphyria (a rare genetic metabolic disorder),
• if you areallergic(hypersensitive) to estriol or any of the other components of Gelistrol(included in section 6 “Additional Information”).

If any of the above conditions appear for the first time while taking Gelistrol, 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 suffer or have suffered from any of the following diseases/disorders, which may rarely recur or worsen during treatment with Gelistrol. If so, you should visit your doctor more frequently for medical check-ups:

• very high levels of fat in the blood (triglycerides)

• growth of tissue that covers the inside of the uterus outside of it (endometriosis) or history of excessive growth of tissue that covers the uterus (endometrial hyperplasia)
• fibroids inside the uterus
• high blood pressure
• diabetes
• gallstones
• 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
• if you experience migraine or severe headache for the first time
• pregnancy
• if any of thecircumstancesdescribed in the section “Do Not Use Gelistrol” occur.
• if you experience signs of 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 an alternative.

Note: Gelistrol is not a contraceptive. If you have passed less than 12 months since your last 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

Long-term use of hormone replacement therapy containing only estrogen may increase the risk of developing endometrial cancer (cancer of the endometrium).

It is not clear if there is a similar risk withGelistrolwhen used for repeated or long-term treatments (more than one year). However, it has been shown that the absorption ofGelistrolinto 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, Gelistrol 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 Gelistrol, 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 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 Gelistrol does not increase the risk of breast cancer in women who have not had breast cancer in the past. It is not known if Gelistrol can be used safely in women who have had breast cancer in the past.

Check your breasts regularly. Visit your doctor if you notice any changes such as:

• lumps in the skin
• changes in the nipple
• any lump that you can see or feel

Additionally, you are recommended to participate in mammography screening programs when offered.

Ovarian Cancer

Ovarian cancer is rare: much rarer than breast cancer. The use of HRT containing estrogen only 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 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., around 1 additional case).

Effect of Hormone Replacement Therapy on the Heart and Circulation

Vein Thrombosis

The risk ofvein thrombosisis 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 dislodges and travels to the lungs, it can cause chest pain, shortness of breath, fainting, or even death.

The probability of having a blood clot increases with age and if you are affected by any of the following situations. Inform your doctor if you are affected by any of these situations:

• you are unable to walk for a long period due to 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,
• if a close relative has had a blood clot in the leg, lung, or other organ,
• you have systemic lupus erythematosus (SLE),
• you have cancer.

Comparison

Average of 4 to 7 out of 1,000 women aged 50 who are not taking hormone replacement therapy, over a 5-year period, may have a blood clot in a vein. In women aged 50 who have been taking 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 around 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

Average of 8 out of 1,000 women aged 50 who are not taking hormone replacement therapy, over a 5-year period, may have a stroke. In women aged 50 taking hormone replacement therapy for more than 5 years, there will be 11 cases per 1,000 users (i.e., 3 additional cases).

Using Gelistrol with Other Medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription, herbal or natural products.

As Gelistrol 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 Gelistrol if you are pregnant.

If you become pregnant during treatment, inform your doctor immediately and do not use Gelistrol.

You should not use Gelistrol during breastfeeding.

Driving and Using Machines

Gelistrol does not affect your ability todrive and use machines.

Gelistrol 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 Gelistrol 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 applicator, consisting of the cannula and plunger, in the following drawing.

1. Unscrew the cap from the tube,invert 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 the cannula and 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 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 10 g – 1 Blister with 10 disposable cannulas and 1 reusable plunger
• Tube of 30 g – 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 warm and clean 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 warm and clean water to be able to use them again for the next application.

If you use more Gelistrol than you should

If too much gel is applied or someone has accidentally ingested some gel, do not worry. You may feel unwell and in some women, vaginal bleeding may occur 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 useGelistrol

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 Gelistrol” 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 patients, these side effects disappear with continued use.Inform your doctor in case of vaginal bleeding 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.

Less frequent side effects (may affect up to 1 in 100 patients):

• 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 like Gelistrol:

• Deep vein thrombosis in the legs or lungs.
• Ovarian cancer.
• Stroke.
• Probable memory loss if THS is started after 65 years of age.

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:

• Pigmentation of the skin, 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 of 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 ofGelistrol

The active ingredient 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 Gelistrol and packaging contents

This medication is an incolore, 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 Gelistrol 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 Gelistrol 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 30 g tube of Gelistrol 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 Gelistrol 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.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

ITALFARMACO, S.A.

San Rafael, 3 -28108 Alcobendas (Madrid)

Responsible manufacturer for release:

ITALFARMACO, S.A.

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

Local representative

Laboratorios EFFIK S.A.

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

Tel:+ 34 91 3585273

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

• Spain:Gelistrol 50 micrograms/g vaginal gel
• Sweden:Gelistrol 50 mikrogram/g vaginal gel
• France:Gelistrol 50 microgrammes/g gel vaginal
• Italy:Gelistrol 50 microgrammi/g gel vaginale
• Portugal:Gelistrol 50 microgramas/g gel vaginal
• Greece:Gelistrol μικρογραμμ?ρια/g κολπικ? γ?λη

Last review date of this leaflet:March 2022

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