ANGELIQ 1 mg/2 mg FILM-COATED TABLETS

• If you have or have had breast canceror if you suspect you may have it.
• If you have a cancer that depends on the action of estrogens, such as cancer of the lining of the uterus (endometrium), or if you suspect you may have it.
• If you have unusual vaginal bleeding.
• If you have an excessive thickening of the lining of the uterus(endometrial hyperplasia).
• If you have or have had a blood clot in a vein(thrombosis), e.g. in the legs (deep vein thrombosis) or in the lungs(pulmonary embolism).
• If you have a blood clotting disorder(such as protein C, protein S or antithrombin deficiency).
• If you have or have recently had a disease caused by blood clots in the arteries, such as a heart attack, a stroke or angina.
• If you have or have had a liver diseaseand your liver function tests have not returned to normal.
• If you have a rare blood disorder called porphyriathat is inherited from your parents.
• If you have severe kidney failure or acute kidney failure.
• If you are allergic(hypersensitive) to estrogens, progestogens or any of the other components of Angeliq (listed in section 6).

If any of these diseases occur for the first time while you are taking Angeliq, stop treatment and consult your doctor immediately.

Warnings and precautions

Consult your doctor or pharmacist before starting Angeliq. Before starting treatment, inform your doctor if you have ever had any of the following problems, as they may return or worsen during treatment with Angeliq. If so, you should visit your doctor more frequently for check-ups:

• fibroids in the uterus
• growth of the lining of the uterus outside the uterus (endometriosis) or a history of excessive growth of the lining of the uterus (endometrial hyperplasia)
• increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)")
• increased risk of developing a cancer that depends on the action of estrogens (e.g. having a mother, sister or grandmother who has had breast cancer)
• high blood pressure
• a liver disorder, such as a benign liver tumor
• diabetes
• gallstones
• migraines or severe headaches
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• a disease that affects the eardrum and ear (otosclerosis)
• a very high level of fats in the blood (triglycerides)
• fluid retention due to heart or kidney problems
• hereditary and acquired angioedema

Stop taking Angeliq and see a doctor immediately

If you notice any of the following conditions while taking HRT:

• any of the conditions mentioned in the section "Do not take Angeliq"
• a yellowish color of the skin or the whites of the eyes (jaundice). This may be a sign of liver disease
• swelling of the face, tongue or throat and difficulty swallowing or hives accompanied by difficulty breathing, suggesting angioedema
• a significant increase in blood pressure (symptoms may be headache, fatigue, dizziness)
• migraine-like headaches when they appear for the first time
• • painful swelling and redness of the legs
  • sudden chest pain
  • difficulty breathing

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

Note: Angeliq 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 method to prevent pregnancy. Ask 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 HRT with estrogens alone will increase the risk of developing excessive thickening of the lining of the uterus (endometrial hyperplasia) and cancer of the lining of the uterus (endometrial cancer). The progestogen in Angeliq protects against this additional risk.

Irregular bleeding

You may have irregular bleeding or spotting during the first 3-6 months of taking Angeliq. However, if irregular bleeding:

• continues for longer than the first 6 months
• starts after you have been taking Angeliq for more than 6 months
• continues after stopping treatment with Angeliq

consult your doctor as soon as possible.

Breast cancer

Existing data show that the use of hormone replacement therapy (HRT) with combined estrogen-progestogen or estrogen-only increases the risk of breast cancer. The additional risk depends on the duration of HRT use. The additional risk becomes apparent after 3 years of use. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT has been used for more than 5 years.

Comparison

In women aged 50-54 who are not taking HRT, on average 13 to 17 out of every 1,000 will be diagnosed with breast cancer over a 5-year period.

In women aged 50 who start estrogen-only HRT for 5 years, there will be between 16 and 17 cases per 1,000 users (i.e. between 0 and 3 additional cases).

In women aged 50 who start taking combined estrogen-progestogen HRT for 5 years, there will be 21 cases per 1,000 users (i.e. between 4-8 additional cases).

In women aged 50-59 who are not taking HRT, on average 27 cases of breast cancer will be diagnosed per 1,000 women over a 10-year period.

In women aged 50 who start estrogen-only HRT for more than 10 years, there will be 34 cases per 1,000 users (i.e. 7 additional cases).

In women aged 50 who start taking combined estrogen-progestogen HRT for 10 years, there will be 48 cases per 1,000 users (i.e. 21 additional cases).

You should have regular breast examinations. Consult your doctor if you notice any change, such as:

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

In addition, it is recommended that you participate in breast cancer screening programs when offered. For breast cancer screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are taking HRT, as these medications may increase breast density, which can affect the outcome of the mammogram. When breast density is increased, the mammogram may not detect all lumps.

Ovarian cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogen alone or with combined estrogen-progestogen 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 cases of ovarian cancer per 2,000 women will be diagnosed over a 5-year period. In women taking HRT for 5 years, approximately 3 cases per 2,000 patients will be diagnosed (i.e. approximately 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 compared to non-users, especially during the first year of use.

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

You are more likely to have a blood clot in the veins with age and if any of the following apply to you. Inform your doctor if any of these situations apply to you:

• you are unable to walk for a long time due to major surgery, injury or illness (see also section 3, If you need to have surgery)
• you are severely overweight (BMI > 30 kg/m²)
• you have a blood clotting disorder that requires long-term treatment with a medication used to prevent blood clots
• any of your close relatives have had a blood clot in the leg, lung or other organ
• you have systemic lupus erythematosus (SLE)
• you have cancer.

For symptoms of a blood clot, see "Stop taking Angeliq and see a doctor immediately".

Comparison

In women in their 50s who are not taking HRT, on average 4 to 7 out of every 1,000 will have a blood clot in a vein over a 5-year period.

In women in their 50s who have been taking combined estrogen-progestogen HRT, there will be 9 to 12 cases per 1,000 users (i.e. 5 additional cases) over a 5-year period.

Heart disease (heart attack)

There is no evidence that HRT prevents heart attacks.

Women over 60 years old who use combined estrogen-progestogen HRT are slightly more likely to develop heart disease than those who do not take HRT.

Stroke

The risk of having a stroke is approximately 1.5 times higher in HRT users compared to non-users. The number of additional stroke cases due to HRT use will increase with age.

Comparison

In women in their 50s who are not taking HRT, on average 8 out of every 1,000 will have a stroke over a 5-year period. For women in their 50s who are taking HRT, there will be 11 cases per 1,000 users over a 5-year period (i.e. 3 additional cases).

Other diseases

• HRT does not prevent memory loss. There is some evidence of greater memory loss in women who start using HRT after the age of 65. Consult your doctor.

• If you have a kidney disorderand have high serum potassium levels, particularly if you are taking other medications that increase serum potassium levels, your doctor should monitor your serum potassium levels during the first month of treatment.
• If you have high blood pressure, you may experience a decrease in blood pressure during treatment with Angeliq. Angeliq should not be used to treat high blood pressure.
• If you tend to develop skin discoloration patches(chloasma) on your face, avoid exposure to the sun or ultraviolet radiation while taking Angeliq.

Using Angeliq with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Some medicines may interfere with the effect of Angeliq, which may lead to irregular bleeding. These medicines are:

• medicines for epilepsy(such as barbiturates, phenytoin, primidone, carbamazepine, oxcarbazepine, topiramate and felbamate)
• medicines for tuberculosis(such as rifampicin and rifabutin)
• medicines for HIV and hepatitis C virus infections(called protease inhibitors and non-nucleoside reverse transcriptase inhibitors, such as nevirapine, efavirenz, nelfinavir and ritonavir)
• herbal products containing St. John's Wort(Hypericum perforatum)
• medicines for fungal infections(such as griseofulvina, itraconazole, ketoconazole, voriconazole, fluconazole)
• medicines for bacterial infections(such as clarithromycin, erythromycin)
• medicines for certain heart diseases, high blood pressure(such as verapamil, diltiazem)
• grapefruit juice

HRT may affect the performance of other medicines:

• A medicine for epilepsy(lamotrigine), as it may increase the frequency of seizures.
• medicines for hepatitis C virus(e.g. combination treatment for HCV ombitasvir/paritaprevir/ritonavir with or without dasabuvir or glecaprevir/pibrentasvir) may cause elevated liver function test results (increase in liver enzyme ALT) in women using HRT with ethinylestradiol. Angeliq contains estradiol instead of ethinylestradiol. It is not known whether liver enzyme ALT may increase when using Angeliq with this combination treatment for HCV.

The following medicines may cause small increases in serum potassium levels:

• medicines used to treat:
• inflammationor pain(e.g. aspirin, ibuprofen)
• certain types of heart diseaseor high blood pressure(e.g. diuretics, ACE inhibitors (e.g. enalapril), angiotensin II receptor antagonists (e.g. losartan)). If you are being treated for high blood pressure and are taking Angeliq, you may have an additional decrease in blood pressure.

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

Your doctor will inform you about this.

Lab tests

If you need a blood test, inform your doctor or the laboratory staff that you are taking Angeliq, because this medicine may affect the results of some tests.

Pregnancy and breastfeeding

Angeliq is indicated in postmenopausal women.

If you become pregnant while taking Angeliq, you should stop treatment immediately and contact your doctor.

Driving and using machines

There are no data to suggest that Angeliq affects the ability to drive or use machines.

Angeliq contains lactose

Angeliq contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Angeliq

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. Your doctor will decide the duration of the treatment.

Take one tablet once a day, preferably at the same time. Swallow the tablet whole with water. You can take Angeliq with or between meals. Start the next calendar pack the day after the current pack is finished.

Do not take a break between packs.

If you have been treated with other THS medications: continue your treatment until you finish the current pack and have taken all the tablets for this month. Take your first Angeliq tablet the next day. Do not take a break between the previous tablets and the Angeliq tablets.

If this is your first treatment with THS: you can start the treatment with Angeliq on any day.

If you take more Angeliq than you should

An overdose may cause nausea and vomiting and irregular bleeding. No specific treatment is necessary, but consult your doctor if you are concerned.

If you have taken more Angeliq than you should, consult your doctor or pharmacist immediately, or call the Toxicology Information Service (Tel: 91 562 04 20) indicating the medication and the amount used.

If you forget to take Angeliq

If you have forgotten to take the tablet at your usual time and less than 24 hours have passed, you should take it as soon as possible. Take the next tablet at the usual time.

If more than 24 hours have passed, leave the forgotten tablet in the pack. Continue taking the rest of the tablets at the usual time every day. Do not take a double dose to make up for the forgotten tablets.

If you forget to take the tablets for several days, irregular bleeding may occur.

If you interrupt the treatment with Angeliq

You may start to notice the symptoms of menopause again, which may include hot flashes, sleep disorders, nervousness, dizziness, or vaginal dryness. You will also start to lose bone mass when you stop taking Angeliq. Consult your doctor or pharmacist if you want to interrupt the treatment with Angeliq. If you have any other questions about the use of this medication, ask your doctor or pharmacist.

If you need to have surgery

If you are going to have surgery, inform the surgeon that you are taking Angeliq. You may need to interrupt the treatment with Angeliq for about 4 to 6 weeks before the surgery to reduce the risk of blood clots (see also section 2 "Blood clots in a vein"). Ask your doctor when you can resume the treatment with Angeliq.

4. Possible side effects

Like all medications, Angeliq can cause side effects, although not all people experience them.

The following diseases occur more frequently in women who use THS compared to women who do not take THS:

• breast cancer
• abnormal growth or cancer of the inner lining of the uterus (endometrial hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• coronary heart disease
• stroke
• possible memory loss if THS is started after 65 years of age.

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

Like all medications, Angeliq can cause side effects, although not all people experience them.

The following list of side effects has been associated with the use of Angeliq

Very common side effects(affect more than 1 in 10 patients):

• unexpected bleeding similar to menstruation (see also section 2 "THS and cancer")
• breast tenderness
• breast pain

During the first few months of treatment with Angeliq, unexpected bleeding similar to menstruationmay appear. It is usually temporary and normally disappears with continued treatment. If it does not, consult your doctor.

Common side effects(affect between 1 and 10 in 100 patients):

• depression, mood changes, nervousness
• headache
• abdominal pain, nausea, abdominal enlargement
• breast lumps (benign breast neoplasm), breast enlargement
• enlargement of uterine fibroids
• non-cancerous growth of cervical cells (benign cervical neoplasm)
• menstrual disorder
• vaginal discharge
• loss of energy, localized fluid retention

Uncommon side effects(affect between 1 and 10 in 1,000 patients):

• weight gain or loss, loss or increase of appetite, increase in blood fats
• sleep disorders, anxiety, decreased sexual desire
• prickling or feeling of heat, decreased ability to concentrate, dizziness
• eye disorder (e.g. red eyes), visual disturbance (e.g. blurred vision)
• palpitations
• blood clots, venous thrombosis (see also section 2 "Blood clots in a vein (thrombosis)"), hypertension, migraine, vein inflammation, varicose veins
• breathing difficulties
• gastrointestinal disorder, diarrhea, constipation, vomiting, dry mouth, flatulence, alteration of taste
• alteration of liver enzymes (will be reflected in blood tests)
• skin problems, acne, hair loss, skin itching, excess hair
• back pain, joint pain, limb pain, muscle cramps
• urinary tract disorders and infections
• breast cancer, hypertrophy of the inner lining of the uterus, unusual benign growth in the uterus, thrush, vaginal dryness and itching
• breast lumps (fibrocystic breasts), disorders of the ovaries, cervix, and uterus, pelvic pain
• generalized fluid retention, chest pain, general discomfort, increased sweating

Rare side effects(affect between 1 and 10 in 10,000 patients):

• anemia
• dizziness
• ringing in the ears
• gallstones
• muscle pain
• inflammation of the Fallopian tubes
• milk secretion through the nipples
• chills

The following side effects have been collected from clinical studies conducted in women with high blood pressure:

• increase in blood potassium levels (hyperkalemia), which sometimes causes muscle cramps, diarrhea, nausea, dizziness, or headache
• heart failure, increase in heart size, palpitations, effects on heart rhythm
• increase in blood aldosterone levels.

The following side effects have been reported in relation to other medications used in THS:

• gallbladder disease
• various skin disorders:

• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma)
• red, painful nodules on the skin (erythema nodosum)
• skin rash with redness in a target shape or sores (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 Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Angeliq

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the blister pack after "EXP". The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE collection 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

Composition of Angeliq

The active ingredients are estradiol (as estradiol hemihydrate) and drospirenone; each tablet contains 1 mg of estradiol and 2 mg of drospirenone.

The other ingredients are lactose monohydrate, cornstarch, pregelatinized cornstarch, povidone, and magnesium stearate (E470b). The coating ingredients are hypromellose (E464), macrogol 6000, talc (E553b), titanium dioxide (E171), and red iron oxide (E172).

Appearance of the product and package contents

Angeliq film-coated tablets are red, round, and convex. One side is marked with the letters DL inside a regular hexagon.

Each pack contains a blister pack with 28 tablets with the days of the week printed on the blister pack. There are packs of one or three blister packs.

Marketing authorization holder

Bayer Hispania, S.L.

Av. Baix Llobregat, 3 - 5

08970 Sant Joan Despí – Barcelona

Spain

Manufacturer

Bayer AG

Müllerstrasse 178

13353 Berlin

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

Angeliq – Belgium, Croatia, Czech Republic, Estonia, Germany, Finland, France, Ireland, Italy, Lithuania, Latvia, Luxembourg, Malta, Netherlands, Poland, Portugal, Slovenia, Spain.

Date of the last revision of this leaflet:January 2024

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