Gelistrol 50 micrograms/g vaginal gel

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Gelistrol 50 micrograms/g vaginal gel

Estriol

Read the entire 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 only and must not be given to other people, even if they have the same symptoms as you, since it could harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Gelistrol is and what it is used for
2. What you need to know before using Gelistrol
3. How to use Gelistrol
4. Possible side effects
5. How to store Gelistrol
6. Contents of the pack and other information

1. What Gelistrol is and what it is used for

Gelistrol belongs to a group of medicines called local vaginal hormone replacement therapy (HRT).

It is used to relieve menopausal vaginal symptoms such as dryness or irritation. Medically, this condition is known as "vaginal atrophy". It is caused by a decrease in estrogen levels in your body and occurs naturally after menopause.

Gelistrol works by restoring the estrogen that is normally produced by the ovaries. It is inserted into the vagina, allowing the hormone to be released exactly where it is needed, thereby relieving vaginal discomfort.

2. What you need to know before starting Gelistrol

Medical history and medical check-ups

The use of hormone replacement therapy carries risks that must be considered when starting or continuing treatment.

Before you begin (or restart) hormone replacement therapy, your doctor will ask about your personal and family medical history. 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 taking Gelistrol, you should visit your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Gelistrol.

Have mammograms regularly, as recommended by your doctor.

Do not use Gelistrol

• If any of the following conditions apply to you or if you have any doubts about any of them, consult your doctor before using Gelistrol:
• if you have, have had, or suspect you may have breast cancer,
• if you have or suspect you may have estrogen-sensitive cancer, such as endometrial cancer (lining of the uterus),
• if you have vaginal bleeding of unknown cause,
• if you have untreated abnormal growth of the endometrium (endometrial hyperplasia),
• if you currently have or have previously had 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 currently have or have recently had arterial diseases caused by blood clots, such as stroke, angina, or heart attack,
• if you currently have acute liver disease and your liver function tests have not returned to normal,
• if you have porphyria (a rare inherited metabolic disorder),
• if you are allergic (hypersensitive) to estriol or to any of the other components of Gelistrol (listed in section 6 “Additional information”).

If any of the above conditions develops for the first time while you are taking Gelistrol, stop taking it immediately and consult your doctor without delay.

Warnings and precautions

This medicine 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 conditions or disorders, which may rarely reappear or worsen during treatment with Gelistrol. If so, you should have medical check-ups more frequently:

• very high levels of fat in the blood (triglycerides)
• growth of tissue lining the inside of the uterus outside the uterus (endometriosis) or history of excessive growth of the tissue lining the uterus (endometrial hyperplasia)
• fibroids within the uterus
• high blood pressure
• diabetes
• gallstones
• migraine or severe headache
• a rare immune disease called systemic lupus erythematosus (SLE)
• epilepsy (seizures)
• asthma
• a condition affecting 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 (for example, if your mother, sister, or grandmother had breast cancer)
• a liver disorder, such as a benign liver tumor
• hereditary and acquired angioedema

Reasons to see your doctor immediately

• jaundice (yellowing of the whites of the eyes and skin) or liver disorders
• sudden increase in blood pressure
• if you experience migraine or severe headache for the first time
• pregnancy
• if any of the circumstances described in the section “Do not use Gelistrol” occur
• if you experience signs of a blood clot, such as:
  • painful swelling and redness of the 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 discontinue treatment and offer an alternative.

Note: Gelistrol is not a contraceptive. If less than 12 months have passed since your last period or if you are under 50 years of age, you may need to use additional contraceptive methods to prevent pregnancy. Talk to your doctor for advice.

Hormone replacement therapy and cancer

Excessive thickening of the tissue lining the inside of the uterus (endometrial hyperplasia) and cancer of the tissue lining the inside of the uterus

Taking oral HRT tablets containing only estrogen over a long period may increase the risk of developing cancer of the lining of the uterus (endometrium).

It is unclear whether a similar risk exists with Gelistrol when used for repeated or long-term treatment (more than one year). However, absorption of Gelistrol into the bloodstream has been shown to be very low; therefore, adding a progestogen is not necessary.

If you experience bleeding or spotting, this is usually not a cause for concern, but you should schedule an appointment with your doctor. It could be a sign that the endometrium has become thicker.

The following risks apply to hormone replacement therapy (HRT) medicines that circulate in the bloodstream. However, Gelistrol is used for local treatment in the vagina, and absorption into the bloodstream is very small. It is less likely that the disorders listed below will worsen or reappear during treatment with Gelistrol, but you should see your doctor if you are concerned.

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

Breast cancer

Available data indicate that using Gelistrol does not increase the risk of breast cancer in women who have not previously had breast cancer. It is not known whether Gelistrol can be used safely in women who have previously had breast cancer.

Examine your breasts regularly. See your doctor if you notice any changes such as:

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

In addition, you are advised to participate in mammography 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 slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 years who do not take HRT, approximately 2 out of 2,000 women will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2,000 users (i.e., about 1 additional case).

Effect of hormone replacement therapy on the heart and circulation

Blood clots in a vein

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

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

The likelihood of having a blood clot in the veins increases with age and if you are affected by any of the following conditions. Inform your doctor if any of these apply to you:

• you are unable to walk for a prolonged period due to major surgery, injury, or illness,
• you are significantly overweight (BMI >30 kg/m²),
• you have a blood clotting disorder requiring long-term treatment with a medication to prevent blood clots,
• if a close relative has had a blood clot in the leg, lung, or another organ,
• you have systemic lupus erythematosus (SLE),
• you have cancer.

Comparison

On average, 4 to 7 out of every 1,000 women in their 50s who are not on hormone replacement therapy may experience a blood clot in a vein over a 5-year period. Among women in their 50s who have used estrogen-only hormone replacement therapy for more than 5 years, there will be 5 to 8 cases per 1,000 users (i.e., 1 additional case).

Heart disease (myocardial infarction)

Women taking estrogen-only therapy do not have an increased risk of developing heart disease.

Stroke

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

Comparison

On average, 8 out of every 1,000 women in their 50s who are not on hormone replacement therapy may have a stroke over a 5-year period. Among women of the same age on 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 medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription, herbal medicines, or other natural products.

Since Gelistrol contains a very low dose of estriol and is intended for local treatment, interactions with other medicines are not expected. 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 medicine.

You must not use Gelistrol if you are pregnant.

If you become pregnant during treatment, inform your doctor immediately and stop using Gelistrol.

You must not use Gelistrol while breastfeeding.

Driving and using machines

Gelistrol does not affect the ability to drive or use machines.

Gelistrol contains

Methylparahydroxybenzoate sodium salt (E 219) and propylparahydroxybenzoate sodium salt (E 217).

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

3. How to use Gelistrol

Follow exactly the administration instructions for Gelistrol provided by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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

Use the applicator to insert the gel into the vagina (preferably before going to bed).

Your doctor will aim to prescribe the lowest dose necessary to treat your symptoms for the required duration. Consult your doctor if you think this dose is too strong or not strong enough.

The following instructions explain how to use the gel.

In the following illustration, you can see all components of the tube and the applicator, which consists of the cannula and the plunger.

1. Unscrew the cap from the tube, turn the cap over, and use the sharp tip to pierce the seal on the neck of the tube. Do not use if the seal is broken.

1. Remove the cannula and plunger. Insert the white plunger into the cannula. Screw the cannula onto the end of the tube.

1. Squeeze the tube to fill the applicator with gel up to the filling mark. The applicator will stop at the mark.

1. Unscrew the cannula from the tube and replace the cap on the tube.

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

1. After use

• 10 g tube – 1 Blister pack containing 10 disposable cannulas and 1 reusable plunger
• 30 g tube – 3 Blister packs containing 30 disposable cannulas and 1 reusable plunger

Remove the plunger from the cannula, discard the cannula, and clean the plunger thoroughly with clean, warm water so it can be reused for the next application.

• 10 g tube – 1 Bag containing 1 reusable cannula and 1 reusable plunger
• 30 g tube – 1 Bag containing 1 reusable cannula and 1 reusable plunger

Remove the plunger from the cannula and clean both the cannula and the plunger thoroughly with clean, warm water so they can be reused for the next application.

If you use more Gelistrol than you should

If too much gel is applied or if someone accidentally ingests some of the gel, do not worry. You may feel nauseous, and in some women, vaginal bleeding may occur after a few days.

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

If you forget to use Gelistrol

Do not use a double dose to make up for missed doses.

Apply the missed dose as soon as you remember, unless more than 12 hours have passed. In that case, simply skip the missed dose.

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

4. Possible adverse effects

Like any other medicine, this medicine may cause adverse effects, although not everyone experiences them.

Tell your doctor immediately if any of the situations described in the section "What you need to know before starting to use Gelistrol" occur, such as vaginal bleeding. Your doctor may need to stop treatment and offer you another alternative.

At the beginning of treatment, irritation or itching in the vagina may occur. In most patients, these adverse effects disappear with continued use. Inform your doctor if you experience vaginal bleeding or if any of the following adverse effects worsen or persist.

Common adverse effects (may affect up to 1 in 10 people):

• Itching, irritation inside or around the vagina.

Uncommon adverse 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 systemic hormone replacement therapy (HRT) that circulates in the bloodstream, compared to women not using HRT. These risks occur less frequently with treatments administered vaginally, such as Gelistrol:

• Blood clots in the veins of the legs or lungs (venous thromboembolism).
• Ovarian cancer.
• Stroke.
• Possible memory loss if HRT is started after age 65.

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

The following adverse effects have been reported with other hormone replacement therapies:

• gallbladder diseases,

• various skin disorders:

• skin pigmentation, especially on the face or neck, known as "pregnancy mask" (chloasma),

• painful red nodules on the skin (erythema nodosum),

• skin rash with lesions or red target-shaped papules (erythema multiforme).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Gelistrol

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging.

The expiry date refers to the last day of the month indicated.

Store below 25°C.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of containers and unused medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Gelistrol

The active substance is estriol.

A full applicator filled 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), methylparaben sodium salt (E 219), propylparaben sodium salt (E 217), polycarbophil, carbopol, sodium hydroxide, hydrochloric acid, purified water.

Appearance of Gelistrol and contents of the pack

This medicine is a colourless, transparent or slightly translucent vaginal gel, supplied in an aluminium tube of 10 g or a 30 g tube.

• Presentation 10 g – Blister with 10 disposable applicators (cannulas) and a reusable plunger.

Cardboard box containing one 10 g tube of Gelistrol and one blister with 10 disposable applicators (cannulas) marked with a filling line and one reusable plunger.

• Presentation 10 g – Bag with 1 reusable applicator (cannula) and a reusable plunger.

Cardboard box containing one 10 g tube of Gelistrol and one bag with 1 reusable applicator (cannula) marked with a filling line and one reusable plunger.

• Presentation 30 g – 3 blisters with 10 disposable applicators (cannulas) and one reusable plunger each.

Cardboard box containing one 30 g tube of Gelistrol and three blisters, each containing 10 disposable applicators (cannulas) marked with a filling line and one reusable plunger.

• Presentation 30 g – Bag with 1 reusable applicator (cannula) and a reusable plunger.

Cardboard box containing one 30 g tube of Gelistrol and one bag with 1 reusable applicator (cannula) marked with a filling line and one reusable plunger.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

ITALFARMACO, S.A.

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

Manufacturer responsible 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 medicinal product is authorized in the European Economic Area member states under the following names:

• Spain: Gelistrol 50 microgramos/g gel vaginal
• 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

Date of the most recent revision of this leaflet: March 2022

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/