ESTRING 7.5 micrograms every 24 hours vaginal delivery system

Introduction

Package Leaflet: Information for the Patient

Estring 7.5 micrograms every 24 hours vaginal delivery system

Estradiol hemihydrate

Read this package leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Estring and what is it used for

Estring is a vaginal ring that contains the active ingredient estradiol hemihydrate, which is a naturally occurring form of the main female sex hormone, estrogen.

Women's ovaries produce less and less estrogen as they approach menopause. Low levels of estrogen can cause symptoms such as dryness, inflammation, or itching of the vagina, and this can lead to painful intercourse and an increased tendency to vaginal or urinary infections.

Estring is part of hormone replacement therapy (HRT), which acts locally in the vagina to maintain the proper concentration of estrogen, in order to relieve these symptoms in postmenopausal women. It does not treat other menopause symptoms, such as hot flashes and sweating. Inform your doctor if you also have these problems.

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

Medical examination

Estring may not be suitable for all women. Before you start using Estring, your doctor should ask you about your personal and family medical history. Your doctor may decide to examine your breasts and/or abdomen, and may perform an internal examination, but only if these examinations are necessary for you or if you have any special concerns.

Once you have started hormone replacement therapy, it is recommended that you visit your doctor for regular check-ups (at least once a year). During these check-ups, your doctor may explain the benefits and risks of continuing to use hormone replacement therapy.

Make sure to:

• have regular breast screening tests and cervical smear tests;
• examine your breasts regularlyto detect any changes, such as dimpling of the skin, changes in the nipple, or any lump that you can see or feel.

Do not use Estring if you have any of the following conditions:

• if you are allergic to estradiol or similar medicines to hormone replacement therapy, or to any of the other ingredients of this medicine (listed in section 6);
• hereditary blood disorder (porphyria);

• cancer that is sensitive to estrogen, e.g., endometrial cancer (cancer of the uterus) or if it is suspected that you may have it;

• history or current presence of a "thrombosis" (blood clots that travel through the bloodstream and block blood vessels in the leg or elsewhere in the body; also known as "deep vein thrombosis" [DVT]);

• if you have or have had breast cancer or if it is suspected that you may have it;

• vaginal bleeding that you have not told your doctor about;
• history or current presence of liver disease, in which liver function tests remain abnormal;
• un-treated endometrial hyperplasia (excessive growth of the tissue lining the uterus);
• history or current presence of blocked arteries that could cause cardiovascular disease, such as angina or heart attack;
• blood clotting disorder (thrombophilic disorder, such as protein C, protein S, or antithrombin deficiency).

If any of the above conditions occur for the first time while you are using Estring, stop using it immediately (remove the ring if possible) and consult your doctor immediately.

Warnings and precautions

Talk to your doctor or pharmacist before you start using Estring.

Your doctor will assess your state of health and will explain in detail the benefits and risks of hormone replacement therapy before prescribing you Estring. Inform your doctor if you currently suffer or have suffered in the past from any of the following conditions, to help him decide if treatment with Estring is suitable for you:

• a prolapse (weakening of the structures that support the internal organs) or if you have ever had a prolapse operation;
• you are on long-term treatment with steroids or have problems with your adrenal glands; for example, a condition called Cushing's disease (in which you may have thinning or reddening of the skin);
• vaginal discomfort, bleeding, or pain in the vagina, including irritation or discharge, which may be caused by ulcers or infection;
• if you have a short and narrow vagina, as a result of a previous operation or due to a condition known as vaginal atrophy;
• fluid retention due to kidney or heart problems;
• high levels of triglycerides (a type of fat) in the blood;
• liver disorders (including liver tumors);
• diabetes;
• history of cancer (particularly breast cancer) in your family;
• risk factors for blood clots in the veins (venous thromboembolism or deep vein thrombosis); see below the section 2, which describes the risks of using Estring;
• high blood pressure;
• migraine or severe headache;
• uterine fibroids (growth in the walls of the uterus);
• seizures (epilepsy);
• gallstones;
• autoimmune disease, systemic lupus erythematosus (SLE);
• history of endometrial hyperplasia (an increase in the number of cells in the tissue lining the uterus);
• endometriosis (tissue lining the inside of the uterus found in other places than the uterus);
• hearing problems, caused by scarring in the ear (otosclerosis);
• asthma;
• hereditary and acquired angioedema.

If any of the above conditions worsen or come back while you are using Estring, you should remove the Estring ring and consult your doctor immediately.

Stop using Estring (remove the ring if possible) and consult your doctor immediately

If you notice any of the following symptoms when using HRT, remove the Estring vaginal delivery system and consult your doctor immediately. If you experience difficulty or pain when trying to remove the vaginal ring, do not continue and consult your doctor:

• if you develop any of the conditions mentioned in the section "do not use Estring";
• if you develop yellowing of the skin or the whites of the eyes (jaundice). These can be signs of liver disease;
• if you develop swelling of the face, tongue, and/or throat and/or difficulty swallowing or hives along with difficulty breathing, which are indicative of angioedema;
• if you experience a large increase in blood pressure (symptoms can be headache, fatigue, dizziness);
• if you have headaches similar to migraines that occur for the first time
• if you become pregnant
• if you notice signs of a blood clot such as:
• • painful swelling and redness in the legs
  • sudden chest pain
  • difficulty breathing

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

Note: Estring is not a contraceptive. If it has been less than 12 months since your last menstrual period or if you are under 50 years old, you may still need to use an additional contraceptive to prevent pregnancy. Talk to your doctor for advice.

HRT and cancer

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

Taking estrogen-only HRT tablets for a long time may increase the risk of developing cancer in the lining of the uterus (the endometrium).

It is uncertain whether there is a similar risk with Estring as with repeated or long-term (more than one year) treatments. However, it has been shown that Estring has very low absorption into the bloodstream, so it is not necessary to add a progestagen.

If you have bleeding or spotting, it is usually not a cause for concern, but you should make an appointment with your doctor without delay. It could be a sign that your endometrium has thickened.

The following risks apply to medicines for HRT that circulate in the blood. However, Estring is for local treatment in the vagina and absorption into the blood is very low. It is less likely that the conditions mentioned below will worsen or come back during treatment with Estring, but you should consult your doctor if you are concerned.

Breast cancer

Evidence suggests that taking Estring does not increase the risk of breast cancer in women without a history of breast cancer in the past. It is not known if Estring can be used safely in women who have had breast cancer in the past.

• Regularly check your breasts. Consult your doctor if you notice any changes such as:
• • dimpling of the skin
  • changes in the nipple
  • any lump that you can see or feel

In addition, it is recommended to join early detection programs through mammograms when recommended.

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 who do not take HRT, approximately 2 women in 2,000 will be diagnosed with ovarian cancer during a 5-year period. For 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).

Effects 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 than in non-users, especially during the first year of treatment.

Blood clots can be serious and if they move to the lungs, they can cause chest pain, difficulty breathing, fainting, or even death. This condition is known as pulmonary embolism or PE.

Deep vein thrombosis and pulmonary embolism are examples of a condition called venous thromboembolism or VTE.

It is more likely that you will have a blood clot in your vein as you get older or if any of the following apply to you. Inform your doctor if any of these situations apply to you:

• If you have cancer
• If you are severely overweight
• If you have ever had a blood clot
• If any of your close relatives have had blood clots;
• If you have had one or more miscarriages;
• If you have had a problem with blood clotting that requires treatment with a medicine such as warfarin or acenocoumarol;
• If you spend a long time in bed due to a major operation, injury, or illness;
• If you have a rare disease called systemic lupus erythematosus.

If any of these situations apply to your case, consult your doctor to see if you should use hormone replacement therapy.

In the case of women aged 50 to 60 who do not take hormone replacement therapy:on average, during a 5-year period, it is expected that 4 to 7 out of every 1,000will have a blood clot in a vein.

In the case of women aged 50 to 60 who are taking hormone replacement therapywith only estrogen for a 5-year period, the figure would be 5 to 8 cases per 1,000(i.e., one additional case).

If you suffer:

• a painful swelling of the leg;
• sudden chest pain;
• difficulty breathing.

Consult a doctor as soon as possible and do not use hormone replacement therapy again, until your doctor tells you that you can. These can be signs of a blood clot.

If you are going to have surgery, make sure your doctor is informed. You may need to stop using hormone replacement therapy for about 4 to 6 weeks before the operation, in order to reduce the risk of having a blood clot. Your doctor will tell you when you can start using hormone replacement therapy again.

Heart disease

For women treated only with estrogen therapy, there is no increased risk of developing heart disease

Stroke

The risk of having a stroke is about 1.5 times higher in users of hormone replacement therapy than in non-users.

The number of additional stroke cases due to the use of HRT increases with age. Other reasons that may increase the risk of stroke are:

• aging;
• high blood pressure;
• smoking;
• drinking too many alcoholic beverages;
• an irregular heartbeat.

If you are concerned about any of these thingsor if you have had a stroke in the past,consult your doctor to see if you should use hormone replacement therapy.

In the case of women aged 50 to 60 who do not take hormone replacement therapy:on average, during a 5-year period, it is expected that 8 out of every 1,000will have a stroke.

In the case of women aged 50 to 60 who are taking hormone replacement therapy, the figure would be 11 out of every 1,000during a 5-year period (i.e., 3 extra cases).

• If you suffer:unexplained, migraine-like headaches, with or without vision problems.

Consult a doctor as soon as possible and do not use hormone replacement therapy again, until your doctor tells you that you can. These headaches can be an early warning sign of a stroke.

Other information

Hormone replacement therapy does not prevent memory loss. In a study of women who started using combined hormone replacement therapy or estrogen-only after age 65, a small increase in the risk of dementia was observed.

Women who suffer from hypertriglyceridemia may have large increases in plasma triglycerides, which can cause inflammation of the pancreas (pancreatitis). The symptoms of pancreatitis can include abdominal pain, abdominal swelling, fever, and nausea or vomiting.

Blood tests

If you are going to have blood tests (e.g., to check for excess triglycerides, a type of fat found in the blood), you should inform your doctor that you are using Estring, as these tests may be affected by the use of the vaginal delivery system.

Use of other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

In particular, tell your doctor if you are taking:

• anticonvulsants used to treat epilepsy, such as phenobarbital, phenytoin, or carbamazepine;
• antibiotics such as rifampicin or rifabutin;
• medicines used to treat HIV infection, such as ritonavir, nelfinavir, nevirapine, or efavirenz;
• herbal preparations containing St. John's Wort (Hypericum perforatum).

It is recommended to remove the ring if you are constipated or if you use vaginal preparations.

Pregnancy and breastfeeding

Estring should not be used during pregnancy. If you become pregnant while using Estring, you should stop using Estring immediately (remove the ring if possible) and inform your doctor that you are pregnant. Estring should not be used during breastfeeding.

Consult your doctor or pharmacist before taking any medicine while breastfeeding.

Driving and using machines

There are no special precautions; you can drive or use machines while you feel well.

3. How to use Estring

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. Follow exactly the administration instructions of the medication contained in this prospectus. You should wash your hands well before placing the Estring vaginal delivery system.

To place the Estring vaginal delivery system in the vagina

• Relax and find a position in which you feel comfortable.
• Stand with one foot on a chair or lie on your back with your knees bent upwards.
• With one hand, open the skin folds around the vagina.
• With the other hand, press the ring to make it take on an oval shape.
• Push the ring into the vagina, as far as you can, up and down, towards the bottom of the pouch.
• Finally, wash your hands.

If the ring falls out, it should be rinsed with lukewarm (not hot) water and then reinserted.

While using the Estring vaginal delivery system

At first, you may notice the presence of the ring, but this feeling will disappear. It may take several weeks before the ring has a full effect. As the ring starts to work, you may notice an increase in vaginal lubrication (moisture); this is normal and should be the same as you felt before menopause.

Most women and their partners have found it acceptable to keep the ring in place during sexual intercourse. If you or your partner are uncomfortable with the presence of the ring or find it unacceptable, it can be removed. The ring may move towards the inside of the vagina and become noticeable when straining to evacuate the intestine. If this happens, the ring can be pushed back to its original position with your finger.

If you know you are constipated or have to strain to evacuate the intestine, you should first remove the ring.

To remove the Estring vaginal delivery system from the vagina

• Relax and find a position in which you feel comfortable.
• Stand with one foot on a chair or lie on your back with your knees bent upwards.
• With one hand, open the skin folds around the vagina.
• With the other hand, hook your finger around the ring.
• Gently pull the ring downwards and forwards.
• Finally, wash your hands.

How long should you use the vaginal delivery system (ring)

Each ring should be worn continuously for three months and then replaced with a new ring, if applicable. The maximum recommended duration of continuous treatment is two years. Your doctor will try to give you the minimum effective dose that is possible, and hormone replacement therapy should only continue while the benefits of relief from intense symptoms outweigh the risk.

Systematic checks while using the Estring vaginal delivery system

It is recommended that you have regular screening tests through the national breast cancer and cervical cancer screening program. Your doctor can provide more detailed information about these tests. You are also advised to inform your doctor as soon as possible about any changes you notice in your breasts.

If you stop using the Estring vaginal delivery system (ring)

Your symptoms may return after approximately three weeks.

Use in children

The use of the Estring vaginal delivery system is not recommended in children.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

The following diseases occur more frequently in women who use systemic HRT medications than in those who do not. These risks are lower in treatments administered via the vagina, such as Estring:

• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• stroke
• probable memory loss if HRT is started from the age of 65

For more information on these side effects, see section 2.

If you contract any of the conditions mentioned in the section "Do not use Estring" or experience any of the following side effects, remove the Estring vaginal delivery system and consult your doctor immediately.If you experience any difficulty or pain when trying to remove the vaginal ring, stop and consult your doctor:

• symptoms of an allergic reaction, which may consist of a skin rash, hives, itching of the skin. This occurs frequently (may affect 1 in 100 people who use Estring)
• persistent or intense vaginal discomfort, ulceration, or swelling after ring placement. This occurs in rare cases (may affect 1 in 1000 people who use Estring)

Rare cases have been reported in which the vaginal ring has adhered to the vaginal wall, making it difficult to remove the ring. Some women have required surgery to remove the vaginal ring.

Common side effectsmay affect up to 1 in 10 people who use the Estring vaginal delivery system:

• urinary tract infections;
• infection and itching inside and around the vagina;
• discomfort or pain in the abdominal area (abdomen);
• any persistent sensation of the ring in the vagina or pressure on the bladder or rectum (retrograde passage);
• pain when urinating;
• generalized itching;
• increased sweating.

The symptoms mentioned above occur more frequently in postmenopausal women who are not treated.

Other side effectsreported during treatment with other estrogen therapy forms are:

Very common side effects, affecting 1 in 10 people

• depression
• hair loss
• joint pain
• leg cramps

• unusual or unexpected intermenstrual bleeding or spotting,
• vaginal discharge, breast pain, breast tenderness, breast swelling, nipple discharge;
• weight changes (increase or decrease)
• changes in triglyceride levels (fat particles in the blood)

Common side effects that affect 1 in 100 people

• blood clots in the legs or lungs (see "Do not use Estring" (remove the ring if possible) and consult your doctor immediately)
• vaginal inflammation
• vaginal candidiasis
• changes in sex drive (increased or decreased libido)
• mood changes
• anxiety
• headache or migraine
• dizziness
• difficulty wearing contact lenses
• nausea, feeling of abdominal bloating, abdominal pain;
• gallbladder disease
• skin discoloration, especially on the face or body, known as pregnancy spots (chloasma)
• increased hair growth
• skin rash
• itching
• changes in menstrual flow
• changes in vaginal discharge
• visible swelling of the face or ankles;

The following side effects have been reported with the use of other HRT medications:

Frequency not known(frequency that cannot be estimated from the available data)

• memory loss
• painful red nodules on the skin (erythema nodosum)
• rash with redness in a target shape or sores (erythema multiforme)

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are possible side effects that do not appear in this prospectus. You can also report them directly through the Spanish Medicines Surveillance System for Human Use: www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Estring

Do not store above 25°C.

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the packaging and also on the aluminum paper bag, after CAD or EXP. The expiration date is the last day of the month indicated.

Do not use the Estring vaginal delivery system if it is discolored, deformed, or does not have a smooth surface.

Used vaginal delivery systems (rings) still contain some of the active hormonal component. The used ring should be placed inside the original bag or in a plastic bag; then, it should be sealed and disposed of safely, out of the reach and sight of children.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Estring composition

• The active ingredient of Estring is 2 mg of estradiol hemihydrate, equivalent to 1.94 mg of estradiol.

Each ring releases an average amount of estradiol of 7.5 micrograms every 24 hours, for a period of 90 days.

• The other components are: silicone fluid, barium sulfate, silicone elastomer Q7-4735A, silicone elastomer Q7-4735B.

Appearance of Estring and package contents

The Estring vaginal delivery system is a slightly opaque ring, made of silicone elastomer, with a white core, which contains a deposit with the active ingredient, estradiol hemihydrate.

Estring is packaged individually in a rectangular, heat-sealed bag, consisting of, from outside to inside, polyester / aluminum foil / low-density polyethylene. Each bag is supplied with a tear-off notch on one side; the bag is in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder

Pfizer, S.L.

Avda. de Europa 20-B,

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Manufacturer

Sever Pharma Solutions AB,

Agneslundsvägen, 27,

SE-212 15 Malmö - Sweden.

This medication is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Date of the last revision of this prospectus: 06/2022

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