Estring 7,5 microgramos cada 24 horas sistema de liberacion vaginal

Label: information for the patient

Estring 7.5 micrograms per 24 hours vaginal delivery system

Estradiol hemihydrate

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

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

The ovaries of women produce less and less estrogen as they approach menopause. Low estrogen levels can cause symptoms such as vaginal dryness, inflammation, or itching, which in turn can cause sores or painful sex, and an increased tendency to vaginal or urinary infections.

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

Medical Review

Estring may not be suitable for all women. Before starting to use Estring, your doctor will need to 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 a special concern.

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 advantages and risks of continuing to use hormone replacement therapy.

Make Sure:

• attend regular breast and cervical cytology screening tests;
• regularly examine your breasts, to detect any changes, such as skin dimpling, changes in the nipple, or any lump that you can see or feel.

Do Not Use Estring If You Have:

• if you are allergic to estradiol or to similar medications to hormone replacement therapy, or to any of the other components of this medication (including in section 6);
• hereditary blood disorder (porphyria);

• cancer that is sensitive to estrogen, such as endometrial cancer (cancer of the uterus)or if you suspect that you may have it;

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

• if you have or have had breast canceror if you suspect that you may have it;

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

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

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Estring.

Your doctor will evaluate your health status and explain the advantages and risks of hormone replacement therapy in detail before prescribing Estring. Inform your doctor if you currently suffer or have suffered in the past from any of the following conditions, to help them decide if Estring treatmentis suitable for you:

• prolapse (weakening of the structures that support internal organs) or if you have ever had a prolapse operation;
• long-term treatment with steroids or problems with the adrenal glands, for example, a condition called Cushing's disease (in which you may present with weight loss or skin redness);
• vaginal discomfort, bleeding, or pain, including irritation or discharge, which may be caused by ulcers or infection;
• if you have a short and narrow vagina, due to a previous operation or as a result of a known condition called 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;
• blood clotting risk factors in the veins (venous thromboembolism or deep vein thrombosis); see more information in section 2, in which the risks of using Estring are described;
• 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 of the tissue that covers the uterus);
• endometriosis (tissue of the internal lining of the uterus that is found in other places);
• hearing problems, caused by scarring in the ear (otosclerosis);
• asthma;
• hereditary and acquired angioedema.

If any of the above conditions worsen or appear again while using Estring, you must remove the Estring ring and consult your doctor immediately.

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

If you observe any of the following symptoms when using HRT, remove the vaginal release system of Estring 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 sectiondo not use Estring
• if you develop yellowing of the skin or the white of the eyes (jaundice). These may be signs of liver disease;
• if you develop swelling of the face, tongue, and/or throat and/or difficulty swallowing or rashes along with difficulty breathing, which are indicative of angioedema;
• if you experience a significant increase in blood pressure (the symptoms may be headache, fatigue, dizziness);
• if you have migraines similar to those that occur for the first time
• if you become pregnant
• if you observe 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)

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

HRT and Cancer

Endometrial hyperplasia and endometrial cancer

Taking estradiol-only HRT tablets for a prolonged period may increase the risk of developing cancer in the lining of the uterus (endometrium).

It is uncertain whether there is a similar risk with Estring compared to repeated or long-term treatments (over one year). However, it has been shown that Estring has very low absorption in the blood, so it is not necessary to add a progestogen.

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

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

Breast Cancer

The 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 unknown whether 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:
• • skin dimpling
  • changes in the nipple
  • any lump that you can see or feel

Additionally, it is recommended that you join screening programs through mammograms when recommended.

Ovarian Cancer

Ovarian cancer is rare, much rarer than breast cancer. The use of HRT with estradiol-only has been associated with a slightly higher risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50-54 who do not take 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 approximately 3 cases per 2000 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.

DVT and PE are examples of a condition called venous thromboembolism or VTE.

You are more likely to have a blood clot in your vein as you age or if you apply any of the following situations. 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 spontaneous abortions;
• if you have had a problem with blood clotting that requires treatment with a medication such as warfarin or acenocoumarol;
• if you spend a prolonged period in bed due to a major operation, an injury, or an illness;
• if you have a rare disease called systemic lupus erythematosus.

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

In the case of women aged 50-60 whodo not take hormone replacement therapy:on average, over a 5-year period, it would be expected that 4-7 out of 1,000 would present with a blood clot in a vein.

In the case of women aged 50-60 whoare taking hormone replacement therapyonly with estradiol for a 5-year period, the figure would be 5-8 cases per 1,000 (i.e., one additional case).

If you suffer from:

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

Consult your doctor as soon as possible and do not use more hormone replacement therapy, until your doctor tells you that you can.

If you are to undergo surgery, make sure your doctor is informed. You may need to stop using hormone replacement therapy for a period of4 to6 weeks before the operation, in order to reduce the risk of a blood clot. Your doctor will tell you when you can start using hormone replacement therapy again.

Heart Disease

For women treated only with estradiol HRT, there is no increased risk of developing heart disease

Stroke

The risk of stroke is approximately 1.5 times higher in HRT users than in non-users. The number of additional stroke cases due to HRT use increases with age. Other factors that may increase the risk of stroke are:

• aging;
• high blood pressure;
• smoking;
• excessive drinking;
• irregular heart rhythm.

If you are concerned about any of these thingsorif 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 50-60 whodo not take hormone replacement therapy:on average, over a 5-year period, it would be expected that 8 out of 1,000 would suffer a stroke.

In the case of women aged 50-60 whoare taking hormone replacement therapy,the figure would be 11 out of 1,000, over a 5-year period (i.e., 3 additional cases).

• If you suffer from:dull headaches, of a migrainous type, with or without visual disturbances.

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

Other Information

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

Women with hypertriglyceridemia may experience large increases in plasma triglycerides, which can cause pancreatitis. The symptoms of pancreatitis may include abdominal pain, abdominal swelling, fever, and nausea or vomiting.

Blood Tests

If you are to have blood tests (e.g., to examine the presence of excessive triglycerides, a type of fat found in the blood), you must inform your doctor that you are using Estring,as these tests may be affected by the use of the vaginal release system.

Use of Other Medications

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription.

Specifically, inform your doctor if you are taking:

• anticonvulsants used in the treatment of epilepsy, such as phenobarbital, phenytoin, or carbamazepine;
• antibiotics such as rifampicin or rifabutin;
• medications used to treat HIV infection, such as ritonavir, nelfinavir, nevirapine, or efavirenz;
• preparations based on plants that contain St. John's Wort (Hypericum perforatum).

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

Pregnancy and Breastfeeding

Estring should not be used during pregnancy. If you become pregnant while using Estring, you must 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 medication while breastfeeding.

Driving and Operating Machines

No special precautions are required; you can drive or operate machines as long as you feel well.

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 leaflet. You should wash your hands thoroughly before placing the vaginal release system Estring.

To place the vaginal release system Estring 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 adopt an oval shape.
• Push the ring into the vagina as far as possible, up and down, towards the bottom of the sac.
• Finally, wash your hands.

If the ring falls, it must be rinsed with warm water (not hot) and then reinserted.

While using the vaginal release system Estring

At first, you may feel the presence of the ring, but this sensation will disappear. It may take several weeks for the ring to have a complete 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 leave the ring in place during sexual intercourse. If you or your partner find the presence of the ring uncomfortable or unacceptable, it can be removed. The ring may move towards the inside of the vagina and become noticeable when straining to pass stool. 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 pass stool, you should first remove the ring.

To remove the vaginal release system Estring 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.
• Pull the ring carefully downwards and forwards.
• Finally, wash your hands.

For how long should you use the vaginal release 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 possible, and hormone replacement therapy should continue only while the benefits of symptom relief are greater than the risk.

Systematic examinations while using the vaginal release system Estring

It is recommended that regular screening tests be performed, through the national breast and cervical cancer screening program. Your doctor may provide you with 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 vaginal release system (ring)

Your symptoms may return after approximately three weeks.

Use in children

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following conditions occur more frequently in women using systemic THS medications than in those who do not use them. These risks are lower in treatments administered via vaginal route, such as Estring:

• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• stroke
• probable memory loss if THS is started at 65 years or older

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

If you contract any of the conditions mentioned in the "Do not use Estring" section or experience any of the following side effects, remove the vaginal Estring 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 allergic reaction, which may include skin rash, hives, skin itching. This occurs frequently (may affect 1 in 100 people using Estring)
• persistent or intense vaginal discomfort, ulceration, or swelling after the ring placement. This occurs in rare cases (may affect 1 in 1000 people using Estring)

Rare cases have been reported where the vaginal ring has adhered to the vaginal wall, making it difficult to extract the ring. Some women have needed surgery to remove the vaginal ring.

Thefrequent side effectsmay affect up to 1 in 10 people using the vaginal Estring system:

• urinary tract infection;
• vaginal infection and itching;
• abdominal discomfort or pain;
• any persistent sensation of the ring in the vagina or pressure on the bladder or rectum (retrograde passage);
• painful urination;
• generalized itching;
• increased sweating.

The mentioned symptoms occur more frequently in untreated postmenopausal women.

Other side effectsreported during treatment of patients with other forms of estrogen treatment are as follows:

Frequent 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 secretion;
• weight changes (gain or loss)
• changes in triglyceride levels (fatty particles in the blood)

Frequent side effects affecting 1 in 100 people

• blood clots in the legs or lungs (see stop using Estring (remove the ring if possible) and consult your doctor immediately)
• vaginal inflammation
• vaginal candidiasis
• changes in sex interest (increase or decrease in libido)
• mood changes
• anxiety
• headache or migraine
• dizziness
• difficulty wearing contact lenses
• nausea, feeling of abdominal swelling, abdominal pain;
• gallbladder disease
• skin discoloration, especially on the face or body, known as melasma
• 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 THS medications:

Unknown frequency(frequency that cannot be estimated from available data)

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

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Do not store above 25°C.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and also on the aluminum foil pouch, after CAD or EXP. The expiration date is the last day of the month indicated.

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

Used vaginal release systems (rings) still contain some of the active hormone component. The used ring should be placed inside the original pouch or 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 in the trash. Deposit the containers and medications you do not need at the SIGRE collection pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you do not need. This way, you will help protect the environment.

Composition of Estring

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

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

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

Appearance of Estring and contents of the packaging

The vaginal delivery system Estring is a slightly opaque ring, made of silicone elastomer, with a whitish core, containing a depot with the active principle, hemihydrate of estradiol.

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

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Pfizer, S.L.

Avda. de Europa 20-B,

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Responsible for manufacturing

Sever Pharma Solutions AB,

Agneslundsvägen, 27,

SE-212 15 Malmö - Sweden.

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Last review date of this leaflet: 06/2022

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