Package Insert: Information for the User

Angeliq 1 mg / 2 mg Film-Coated Tablets

estradiol / drospirenone

Angeliq is indicated as hormone replacement therapy (HRT). It contains two types of female hormones, an estrogen and a progestogen. Angeliq is used in postmenopausal women who had their last natural menstrual period more than 1 year ago.

Angeliq is used for:

Relief of symptoms that appear after menopause

During menopause, the amount of estrogen produced by the woman's body decreases. This can cause symptoms such as hot flashes in the face, neck, and chest (“hot flashes”). Angeliq relieves these symptoms after menopause. You will be prescribed Angeliq if your symptoms seriously affect your daily life.

Prevention of osteoporosis

After menopause, women may develop brittle bones (osteoporosis). Consult with your doctor about all available treatment options.

If you have an increased risk of suffering fractures due to osteoporosis and other medications are not suitable for you, you may use Angeliq to prevent osteoporosis after menopause.

Medical History and Regular Reviews

The use of THS involves risks that must be taken into account when deciding whether to start or continue treatment.

The experience in treating women with premature menopause (due to ovarian insufficiency or surgical intervention) is limited. If you have premature menopause, the risks of using THS may be different. Consult your doctor.

Before starting (or resuming) THS, your doctor will ask about your personal and family medical history. Your doctor may decide to perform a physical examination. This may include a breast examination and/or an internal examination, if necessary.

Once started on Angeliq, you must visit your doctor for regular reviews (at least once a year). In these controls, consult with your doctor about the benefits and risks of continuing with Angeliq.

You should have regular breast examinations, as recommended by your doctor.

Do not take Angeliq

if any of the following conditions affect you. If you are unsure about any of the following points,consult your doctorbefore taking Angeliq.

• If you have or have hadbreast canceror if you suspect you may have it.
• If you have acancer that depends on the action of estrogens, such as endometrial cancer, or if you suspect you may have it.
• If you haveabnormal vaginal bleeding.
• If you have anexcessive thickening of the uterine lining(endometrial hyperplasia).
• If you have or have hadblood clots in a vein(deep vein thrombosis) or in the lungs(pulmonary embolism).
• If you have ablood clotting disorder(such as protein C deficiency, protein S deficiency, or antithrombin deficiency).
• If you have or have had recently a disease caused by blood clots in the arteries, such asheart attack, stroke, or angina pectoris.
• If you have or have had aliver diseaseand your liver function tests have not returned to normal.
• If you have a rare blood disorder calledporphyriathat is inherited.
• If you havesevere kidney failure or acute kidney failure.
• If you areallergic(hypersensitive) to estrogens, progestins, or any of the other components of Angeliq (including those in section 6).

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

Warnings and Precautions

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

• fibroids inside the uterus
• growth of the uterine lining outside the uterus (endometriosis) or history of excessive growth of the uterine lining (endometrial hyperplasia)
• increased risk of developing blood clots (seeBlood 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
• liver disease, such as a benign liver tumor
• diabetes
• gallstones
• migraines or severe headaches
• a disease of the immune system that affects many organs in the body (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• a disease that affects the eardrum and ear (otosclerosis)
• very high levels of fat in the blood (triglycerides)
• fluid retention due to heart or kidney problems
• hereditary and acquired angioedema

Stop taking Angeliq and go to your doctor immediately

If you notice any of the following disorders when taking THS:

• any of the disorders mentioned in the sectionNo take Angeliq
• yellowing of the skin or white of the eyes (jaundice). This may be a sign of liver disease
• swelling of the face, tongue, or throat and difficulty swallowing or urticaria accompanied by difficulty breathing, which suggests angioedema
• a significant increase in blood pressure (symptoms may be headache, fatigue, dizziness)
• migraine-type headaches that appear for the first time
• if you become pregnant
• if you notice signs of a blood clot, such as
• • painful and swollen legs
  • sudden chest pain
  • difficulty breathing

For more information, seeBlood Clots in a Vein (Thrombosis)

Note: Angeliq is not an anticonceptive.If you have 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.

THS and Cancer

Excessive thickening of the uterine lining (endometrial hyperplasia) and endometrial cancer.

The use of THS with estrogens alone will increase the risk of developing excessive thickening of the uterine lining (endometrial hyperplasia) and endometrial cancer. The progestin in Angeliq protects against this additional risk.

Irregular Bleeding

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

• continues for more than 6 months
• starts after taking Angeliq for more than 6 months
• continues after stopping treatment with Angeliq

consult your doctor as soon as possible.

Breast Cancer

The existing data show that the use of hormone replacement therapy (HRT) with estrogen-progestin combinations or with estrogens alone 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 using HRT, a mean of 13-17 out of every 1,000 will be diagnosed with breast cancer in a 5-year period.

In women aged 50 who start HRT with estrogens alone 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 HRT with estrogen-progestin 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 using HRT, a mean of 27 cases of breast cancer per 1,000 women will be diagnosed in a 10-year period.

In women aged 50 who start HRT with estrogens alone 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 HRT with estrogen-progestin 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 changes such as:

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

Additionally, it is recommended that you join the breast cancer screening programs when offered. For breast cancer screening, it is essential to inform the nurse/healthcare professional who will perform the radiography that you are a HRT user, as these medications can increase the density of the breasts, which can affect the results of the mammography. When the breast density increases, the mammography may not detect all lumps.

Ovarian Cancer

Ovarian cancer occurs less frequently than breast cancer. The use of HRT with estrogens alone or with estrogen-progestin combinations 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 are not using HRT, approximately 2 cases of ovarian cancer per 2,000 women are observed in a 5-year period. In women taking HRT for 5 years, approximately 3 cases per 2,000 patients (i.e., approximately 1 additional case) are observed.

Effects of HRT on the Heart and Circulation

Blood Clots in a Vein (Thrombosis)

The risk ofblood clots in the veinsis 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 dislodges and 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 conditions affect you. Inform your doctor if any of these situations affect you:

• you cannot walk for a prolonged period due to major surgery, injury, or illness (see also section 3, If you need to undergo surgery)
• you have severe obesity (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, seeStop taking Angeliq and go to your doctor immediately

Comparison

In women aged 50 who are not using HRT, a mean of 4 to 7 out of every 1,000 will have a blood clot in a vein in a 5-year period.

In women aged 50 who have been taking HRT with estrogen-progestin for 5 years, there will be 9 to 12 cases per 1,000 users (i.e., 5 additional cases) in a 5-year period.

Coronary Heart Disease (Heart Attack)

There is no evidence that HRT prevents heart attacks.

Women over 60 years old who are taking HRT with estrogen-progestin are slightly more likely to develop coronary heart disease than those who are not taking any 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 aged 50 who are not using HRT, a mean of 8 out of every 1,000 will have a stroke in a 5-year period. For women aged 50 who are taking HRT, there will be 11 cases per 1,000 users in 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 akidney disorderand have high levels ofserum potassium, particularly if you are taking other medications that increase serum potassium, your doctor will need to monitor serum potassium levels during the first month of treatment.
• If you havehigh blood pressure, you may experience a decrease in blood pressure during treatment with Angeliq. Angeliq should not be used to treat hypertension.
• If you have atendency to developskin discoloration(melasma)on the face, avoid exposure to the sun or ultraviolet radiation while taking Angeliq.

Use of Angeliq with Other Medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. Some medications may interfere with the effect of Angeliq, leading to irregular bleeding. These medications are:

• medications forepilepsy(such as barbiturates, phenytoin, primidone, carbamazepine, oxcarbazepine, topiramate, and felbamate)
• medications fortuberculosis(such as rifampicin and rifabutin)
• medications forinfection with HIVand forinfection with the hepatitis C virus(called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as nevirapine, efavirenz, nelfinavir, and ritonavir)
• preparations based on plants that containSt. John's Wort(Hypericum perforatum)
• medications for thetreatment of fungal infections(such as griseofulvin, itraconazole, ketoconazole, voriconazole, and fluconazole)
• medications for thetreatment of bacterial infections(such as clarithromycin and erythromycin)
• medications for thetreatment of certain heart diseases, high blood pressure(such as verapamil and diltiazem)
• orange juice

HRT may affect the functioning of other medications:

• a medication for epilepsy (lamotrigine), which may increase the frequency of seizures.
• medications for hepatitis C virus (HCV) (e.g., the combination regimen for HCV ombitasvir/paritaprevir/ritonavir with or without dasabuvir or glecaprevir/pibrentasvir) may cause elevations in liver function test results (increased ALT levels) in women taking HRT with ethinyl estradiol. Angeliq contains estradiol instead of ethinyl estradiol. It is unknown whether an increase in ALT levels can occur when Angeliq is used with this HCV combination regimen.

The following medications may cause small increases in serum potassium:

• medications used in the treatment of
• inflammationorpain(e.g., aspirin, ibuprofen)
• certain types of coronary heart diseaseorhigh blood pressure(e.g., diuretics (urine tablets), ACE inhibitors (e.g., enalapril), angiotensin II receptor antagonists (e.g., losartan)). If you are taking medications for high blood pressure and taking Angeliq, you may experience an additional decrease in blood pressure.

Inform your doctor or pharmacist if you are using or have used recently othermedications, including those acquired without a prescription, herbal remedies, and other natural products.

Your doctor will inform you about this.

Laboratory Tests

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

Pregnancy and Breastfeeding

Angeliq is indicated for postmenopausal women.

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

Driving and Operating Machinery

There is no evidence that Angeliq affects the ability to drive or operate machinery.

Angeliq contains lactose

Angeliq contains lactose (a type of sugar). If your doctor has told you that you have anintolerance to certain sugars,consult with them before taking this medication.

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

Do not make a pause 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 of this month. Take your first Angeliq tablet the next day. Do not make a pause between the previous tablets and the Angeliq tablets.

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

If you take more Angeliq than you should

A 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 Toxicological Information Service (Tel: 91 562 04 20) indicating the medication and the amount used.

If you forgot to take Angeliq

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

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

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 disturbances, 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 surgery

If you are going to undergo surgery, inform the surgeon that you are taking Angeliq. You may need to stop taking Angeliq for 4 to 6 weeks before surgery to reduce the risk of blood clot formation (see also section 2 “Blood clots in a vein”). Ask your doctor when you can resume taking Angeliq.

Like all medications, Angeliq may cause side effects, although not everyone will experience them.

The following diseases occur more frequently in women using THS compared to women not taking THS:

• breast cancer
• abnormal growth or cancer of the inner wall of the uterus (endometrial hyperplasia or cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• coronary disease
• stroke
• probable memory loss if THS has been initiated after the age of 65.

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

Like all medications, Angeliq may cause side effects, although not everyone will experience them.

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

More frequent 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 months of treatment with Angeliq, unexpected bleeding similar to menstruation may appearunexpected bleeding similar to menstruation. It is usually temporary and normally disappears with continued treatment. If not, consult your doctor.

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

• depression, mood changes, nervousness
• headache
• abdominal pain, nausea, increased abdomen
• breast lumps (benign breast neoplasia), increased breast size
• increased size of uterine fibroids
• benign growth of cervical cells (benign cervical neoplasia)
• menstrual disorders
• vaginal discharge
• loss of energy, localized fluid retention

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

• weight gain or loss, loss or increase of appetite, increased blood fats
• sleep disorders, anxiety, decreased libido
• pinching or sensation of heat, decreased concentration ability, dizziness
• eye disorders (e.g. red eyes), visual disturbances (e.g. blurred vision)
• palpitations
• blood clots, venous thrombosis (see also section 2 “Blood clots in a vein (thrombosis)”), hypertension, migraine, inflammation of veins, varicose veins
• difficulty breathing
• gastrointestinal disorders, diarrhea, constipation, vomiting, dry mouth, flatulence, altered taste
• alteration of liver enzymes (reflected in blood tests)
• skin problems, acne, hair loss, skin itching, excessive hair growth
• back pain, joint pain, limb pain, muscle cramps
• urinary tract disorders and infections
• breast cancer, uterine wall hypertrophy, unusual benign growth in the uterus, aphthae, vaginal dryness and itching
• breast lumps (fibrocystic breasts), ovarian, cervical and uterine disorders, pelvic pain
• generalized fluid retention, chest pain, general malaise, increased sweating

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

• anemia
• dizziness
• tinnitus
• gallstones
• muscle pain
• inflammation of the Fallopian tubes
• galactorrhea
• chills

The following side effects are listed from clinical studies conducted in women with hypertension:

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

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 red spots or blisters (erythema multiforme)

Reporting of 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 prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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 on the blister after “CAD”. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Angeliq

Theactive principlesare estradiol (as estradiol hemihydrate) and drospirenone; each tablet contains 1 mg of estradiol and 2 mg of drospirenone.

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

Appearance of the product and contents of the packaging

The coated tablets of Angeliq are red, round, and convex. One of the faces is marked with the letters DL within a regular hexagon.

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

Marketing authorization holder

Bayer Hispania, S.L.

Avenida Baix Llobregat, 3 - 5

08970 Sant Joan Despí – Barcelona

Spain

Responsible for manufacturing

Bayer AG

Müllerstrasse 178

13353 Berlin

This medicine 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.

Last review date of this leaflet:January 2024

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