ANGELIQ 1 mg/2 mg Tablets

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Angeliq, 1 mg + 2 mg, coated tablets
   1. Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of Contents of the Leaflet
3. What is Angeliq and what is it used for
   1. Angeliq is used for:
   2. Relief of symptoms occurring after menopause
   3. Prevention of osteoporosis
4. Important information before taking Angeliq
   1. Medical history and regular medical examinations
   2. Regular breast examinations should be performed as recommended by the doctor.
   3. When not to take Angeliq:
   4. If any of the above conditions occur while taking Angeliq, stop taking the medicine and consult a doctor immediately.
   5. Warnings and precautions
   6. Stop taking Angeliq and consult a doctor immediately
   7. HRT and cancer
   8. Endometrial hyperplasia and endometrial cancer
   9. Irregular bleeding
   10. Breast cancer
   11. Ovarian cancer
   12. Effect of HRT on the heart and blood vessels
   13. Blood clots in veins (thrombosis)
   14. Heart disease (heart attack)
   15. Stroke
   16. Other diseases
   17. Angeliq and other medicines
   18. Lab tests
   19. Pregnancy and breastfeeding
   20. Driving and using machines
   21. Angeliq contains lactose
5. How to take Angeliq
   1. Overdose of Angeliq
   2. Missed dose of Angeliq
   3. Stopping Angeliq
   4. Surgery
6. Possible side effects
   1. Reporting side effects
7. How to store Angeliq
8. Contents of the pack and other information
   1. What Angeliq contains
   2. What Angeliq looks like and contents of the pack
   3. Marketing authorization holder
   4. Manufacturer
   5. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   6. Date of last revision of the leaflet: 01/2024

Package Leaflet: Information for the Patient

Angeliq, 1 mg + 2 mg, coated tablets

Estradiol + Drospirenone

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Angeliq and what is it used for
• 2. Important information before taking Angeliq
• 3. How to take Angeliq
• 4. Possible side effects
• 5. How to store Angeliq
• 6. Contents of the pack and other information

1. What is Angeliq and what is it used for

Angeliq is a medicine used in Hormone Replacement Therapy (HRT). It contains two types of female hormones: estrogen and progestogen. Angeliq is used in postmenopausal women, at least one year after their last menstrual period.

Angeliq is used for:

Relief of symptoms occurring after menopause

During menopause, the amount of estrogen produced by the woman's body decreases. This can cause symptoms such as hot flashes on the face, neck, and chest. Angeliq relieves these symptoms occurring after menopause. Angeliq will be prescribed if the symptoms significantly disrupt the patient's daily life.

Prevention of osteoporosis

After menopause, some women may develop brittle bones (osteoporosis). All available treatment options should be discussed with the doctor. In women at high risk of future fractures, who cannot take other medicines, Angeliq may be used to prevent osteoporosis after menopause.

2. Important information before taking Angeliq

Medical history and regular medical examinations

Taking HRT involves risks that need to be considered when deciding whether to start or continue treatment. Experience with treating women with premature menopause (due to ovarian failure or surgery) is limited. In women with premature menopause, the risks associated with HRT may be different. In such cases, consult a doctor. Before starting (or restarting) HRT, the doctor will conduct a medical history and examination of the patient and her family. The doctor may decide to perform a medical examination. The doctor may examine the breasts and (if necessary) perform a gynecological examination. After starting Angeliq, the patient should undergo regular medical examinations (at least once a year). During these visits, the benefits and risks associated with continuing Angeliq should be discussed with the doctor.

Regular breast examinations should be performed as recommended by the doctor.

When not to take Angeliq:

if any of the following conditions apply to the patient. If the patient is unsure whether any of the conditions apply, they should consult a doctor before taking Angeliq.

• if the patient has or has had breast cancer or if its presence is suspected
• if the patient has a tumor that is sensitive to estrogens, such as endometrial cancer (cancer of the lining of the uterus) or if its presence is suspected
• if the patient has unexplained vaginal bleeding
• if the patient has excessive growth of the lining of the uterus (endometrial hyperplasia)
• if the patient has or has had a blood clot in a vein (deep vein thrombosis), for example in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
• if the patient has a known tendency to form blood clots (such as protein C, protein S, or antithrombin deficiency)
• if the patient has or has recently had a disease caused by blood clots in an artery, such as a heart attack, stroke, or angina pectoris
• if the patient has or has had liver disease and liver function tests have not returned to normal
• if the patient has a rare, inherited blood disorder called porphyria
• if the patient has severe kidney disease or acute kidney failure
• if the patient is allergic (hypersensitive) to estrogens, progestogens, or any of the other ingredients of Angeliq (listed in section 6).

If any of the above conditions occur while taking Angeliq, stop taking the medicine and consult a doctor immediately.

Warnings and precautions

Before starting Angeliq, discuss it with your doctor or pharmacist. If the patient has ever had any of the following medical conditions, they should inform their doctor before starting treatment, as these conditions may recur or worsen with Angeliq. In such cases, more frequent check-ups with the doctor are recommended:

• uterine fibroids
• endometriosis or endometrial hyperplasia in the past
• increased risk of blood clots (see below "Blood clots in veins")
• increased risk of estrogen-sensitive tumors (such as breast cancer in the patient's mother, sister, or grandmother)
• high blood pressure
• liver disease, such as a benign liver tumor
• diabetes
• gallstones
• migraine or severe headaches
• an immune system disease that can affect many organs (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• ear and hearing problems (otosclerosis)
• very high levels of fats in the blood (triglycerides)
• fluid retention due to heart or kidney failure
• inherited and acquired angioedema.

Stop taking Angeliq and consult a doctor immediately

If the patient experiences any of the following symptoms while taking HRT:

• any of the conditions listed in the "Do not take Angeliq" section
• yellowing of the skin or whites of the eyes (jaundice) - this may be a sign of liver disease
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives with difficulty breathing, suggesting angioedema
• significant increase in blood pressure (symptoms may include headache, fatigue, dizziness)
• first occurrence of migraine-like headaches
• pregnancy
• symptoms that may indicate a blood clot, such as:
• painful swelling and redness of the legs
• sudden chest pain
• shortness of breath More information can be found in the "Blood clots in veins" section. Note:Angeliq is not a contraceptive. Women who have not had a menstrual period for 12 months or are under 50 years of age may still require additional contraception to prevent pregnancy. Consult a doctor for advice.

HRT and cancer

Endometrial hyperplasia and endometrial cancer

Taking only estrogens in HRT increases the risk of endometrial hyperplasia and endometrial cancer. The progestogen in Angeliq protects against this additional risk.

Irregular bleeding

During the first 3-6 months of taking Angeliq, irregular bleeding or spotting may occur. However, if irregular bleeding:

• persists after 6 months of treatment
• occurs after a period of more than 6 months after starting Angeliq
• persists after stopping Angeliq consult a doctor as soon as possible.

Breast cancer

Evidence suggests that taking combined estrogen-progestogen HRT or estrogen-only HRT increases the risk of breast cancer - this is dependent on the duration of treatment. The increased risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT lasted more than 5 years. Comparison In women aged 50-54 who do not take HRT, breast cancer will be diagnosed in approximately 13-17 per 1,000 women over 5 years. In women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 per 1,000 patients (i.e., 0-3 additional cases). In women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 per 1,000 patients (i.e., 4-8 additional cases). In women aged 50-59 who do not take HRT, breast cancer will be diagnosed in approximately 27 per 1,000 women over 10 years. In women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 per 1,000 patients (i.e., 7 additional cases). In women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 per 1,000 patients (i.e., 21 additional cases).

• The patient should regularly examine their breasts. If any of the following changes occur, consult a doctor:
• retraction or dimpling of the skin
• changes in the nipple
• any noticeable or palpable lumps.

In addition, it is recommended to participate in screening mammography if available. When undergoing screening mammography, it is essential to inform the nurse or medical staff performing the X-ray that HRT is being taken, as this medicine may increase breast density, which can affect the mammography result. With increased breast density, mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking estrogen-only HRT or combined estrogen-progestogen HRT is associated with a slightly increased risk of ovarian cancer. The risk of ovarian cancer depends on age. For example, in women aged 50-54 who do not take HRT, ovarian cancer will be diagnosed over 5 years in approximately 2 per 2,000 women. In women taking HRT for 5 years, ovarian cancer will occur in approximately 3 women per 2,000 patients (i.e., 1 additional case).

Effect of HRT on the heart and blood vessels

Blood clots in veins (thrombosis)

The risk of blood clots in veins is about 1.3 to 3 times higher in women taking HRT, especially in the first year of treatment, than in those not taking HRT. Blood clots can be life-threatening, especially if one travels to the lungs, causing chest pain, shortness of breath, fainting, or even death. The risk of blood clots increases with age and if any of the following conditions apply to the patient. The patient should inform their doctor:

• if the patient is unable to walk for a long time due to major surgery, injury, or illness (see also section 3 "Surgery")
• if the patient is severely overweight (BMI > 30 kg/m²)
• if the patient has blood clotting problems that require long-term administration of medicines to prevent blood clots
• if the patient's close relatives have had blood clots in the legs, lungs, or other organs
• if the patient has systemic lupus erythematosus (SLE)
• if the patient has cancer.

Symptoms that may indicate a blood clot are listed in the "Stop taking Angeliq and consult a doctor immediately" section. Comparison In women around the age of 50 who do not take HRT, it can be expected that over 5 years, 4-7 per 1,000 women will develop a blood clot in the veins. In women around the age of 50 taking combined estrogen-progestogen HRT for over 5 years, 9-12 such cases will occur per 1,000 patients (i.e., 5 additional cases).

Heart disease (heart attack)

It has not been confirmed that HRT prevents heart attacks. In women over 60 years of age taking combined estrogen-progestogen HRT, the risk of heart disease is slightly higher than in women not taking HRT.

Stroke

The risk of stroke in women taking HRT is about 1.5 times higher than in women not taking HRT. The number of additional stroke cases associated with HRT increases with age. Comparison In women around the age of 50 who do not take HRT, it can be expected that over 5 years, 8 per 1,000 women will have a stroke. In women around the age of 50 taking HRT, this value is 11 cases per 1,000 patients over 5 years (i.e., 3 additional cases).

Other diseases

• HRT does not prevent memory loss. There is some evidence suggesting greater memory loss in women starting HRT after the age of 65. For more information, consult a doctor.
• If the patient has kidney problems and high potassium levels in the blood, especially if they are taking medicines that increase potassium levels, the doctor may check potassium levels in the blood during the first month of treatment.
• If the patient has high blood pressure, taking Angeliq may lower it. Angeliq should not be used to treat high blood pressure.
• If the patient is prone to chloasma (skin discoloration), they should avoid sun exposure or ultraviolet radiation while taking Angeliq.

Angeliq and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription, herbal medicines, and other natural products. Some medicines (listed below) may affect the action of Angeliq, which may lead to irregular bleeding:

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

HRT may affect the action of other medicines:

• medicines used to treat epilepsy (lamotrigine), as they may increase the frequency of seizures
• medicines used to treat hepatitis C virus (such as the treatment regimen using ombitasvir/paritaprevir/ritonavir with dasabuvir or without dasabuvir, and the treatment regimen using glecaprevir/pibrentasvir) may cause increased liver function test results in the blood (increased ALT enzyme activity) in women taking combined hormonal contraceptives containing ethinyl estradiol. Angeliq contains estradiol instead of ethinyl estradiol. It is not known whether increased ALT enzyme activity may occur when taking Angeliq with such a hepatitis C treatment regimen.

The following medicines may cause a slight increase in potassium levels in the blood:

• medicines used to treat:
• pain or inflammation(e.g., acetylsalicylic acid, ibuprofen)
• certain heart diseases or high blood pressuresuch as diuretics (water pills), ACE inhibitors (e.g., enalapril), or angiotensin II receptor antagonists (e.g., losartan)

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal medicines, and other natural products. The doctor will provide appropriate guidance.

Lab tests

If a blood test is necessary, inform your doctor or nurse about taking Angeliq, as this medicine may affect the results of some tests.

Pregnancy and breastfeeding

Angeliq is intended for postmenopausal women. If pregnancy occurs, stop taking Angeliq and consult a doctor.

Driving and using machines

There is no evidence that Angeliq affects the ability to drive or use machines.

Angeliq contains lactose

Angeliq contains lactose (a type of sugar). If the patient has been diagnosed with intolerance to some sugars, they should consult a doctor before taking the medicine.

3. How to take Angeliq

Take this medicine always as directed by your doctor. If you are unsure, consult your doctor or pharmacist. The doctor will decide how long to take Angeliq. Take one tablet daily, preferably at the same time. Swallow the tablet whole with water. Angeliq can be taken with or without food. Start the next pack of tablets the next day after finishing the previous one. Do not take a break between packs. If you are taking another HRT medicine:continue taking your current medicine until the pack is finished and all the tablets for that month have been taken. Take the first tablet of Angeliq the next day. Do not take a break between the previous medicine and Angeliq. If HRT is being taken for the first time:you can start taking Angeliq on any day.

Overdose of Angeliq

Overdose may cause nausea, vomiting, and irregular bleeding. There is no need for special treatment, but if you are unsure, consult a doctor.

Missed dose of Angeliq

If you forget to take a tablet at the usual time and the delay is less than 24 hours, take it as soon as possible. Take the next tablet at the usual time. If the delay is more than 24 hours, leave the missed tablet in the pack. Continue taking the remaining tablets at the usual time every day. Do not take a double dose to make up for the missed dose. If you forget to take a tablet for several days, irregular bleeding may occur.

Stopping Angeliq

Typical menopausal symptoms may occur, including hot flashes, sleep disturbances, nervousness, dizziness, or vaginal dryness. Bone density loss may begin after stopping Angeliq. If you want to stop taking Angeliq, discuss it with your doctor or pharmacist. If you have any further questions about taking this medicine, consult a doctor or pharmacist.

Surgery

If you are scheduled for surgery, inform your surgeon that you are taking Angeliq. It may be necessary to stop taking Angeliq about 4-6 weeks before the planned surgery to reduce the risk of blood clots (see section 2 "Blood clots in veins"). Ask your doctor when you can resume taking Angeliq.

4. Possible side effects

Like all medicines, Angeliq can cause side effects, although not everybody gets them. The following diseases are reported more frequently in women taking HRT than in women not taking HRT:

• breast cancer
• abnormal growth or cancer of the lining of the uterus (endometrial hyperplasia or endometrial cancer)
• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• possible memory loss, if HRT is started after the age of 65 Detailed information on these side effects can be found in section 2.

As with any medicine, Angeliq can cause side effects, although not everybody gets them. The following side effects have been associated with Angeliq:

Very common side effects(occurring in at least 1 in 10 patients):

• unexpected bleeding like a menstrual period (see also section 2 "HRT and cancer")
• breast tenderness
• breast pain

Common side effects(occurring in 1-10 per 100 patients):

• depression, mood changes, nervousness
• headache
• abdominal pain, nausea, abdominal distension
• breast lumps (benign breast tumors), breast swelling
• enlargement of uterine fibroids
• non-cancerous growth of cells on the cervix
• irregular vaginal bleeding
• discharge
• weakness, localized fluid retention

Uncommon side effects(occurring in 1-10 per 1,000 patients):

• weight gain or loss, increased or decreased appetite, increased blood fat levels
• sleep disturbances, anxiety, decreased libido
• tingling or burning sensation, decreased concentration, dizziness
• eye problems (e.g., red eyes), vision disturbances (e.g., blurred vision)
• palpitations
• thrombosis, thrombophlebitis (see also section 2 "Blood clots in veins"), high blood pressure, migraine, phlebitis
• shortness of breath
• gastrointestinal disturbances, diarrhea, constipation, vomiting, dry mouth, bloating, taste disturbances
• changes in liver enzyme activity (visible in blood tests)
• skin problems, acne, hair loss, itching, excessive hair growth
• back pain, joint pain, limb pain, muscle cramps
• urinary tract problems, infections
• breast cancer, endometrial hyperplasia, uterine fibroids, thrush, vaginal dryness and itching
• ovarian cysts, cervical and uterine problems, pelvic pain
• generalized fluid retention, chest pain, malaise, increased sweating

Rare side effects(occurring in 1-10 per 10,000 patients):

• anemia
• dizziness
• ringing in the ears
• gallstones
• muscle pain
• salpingitis
• milk secretion from the nipples
• chills

During clinical trials, the following side effects were reported in women with high blood pressure:

• increased potassium levels in the blood (hyperkalemia), sometimes leading to muscle cramps, diarrhea, nausea, dizziness, or headache
• heart failure, cardiac enlargement, palpitations, arrhythmias
• increased aldosterone levels in the blood

The following side effects have been reported with other HRT medicines:

• gallbladder disease
• various skin disorders:
• skin discoloration, especially on the face or neck, known as "pregnancy patches" (chloasma)
• painful red skin lumps (erythema nodosum)
• rash with round red patches or ulcers (erythema multiforme)

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, Al. Jerozolimskie 181C, 02-222 Warszawa, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Angeliq

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the month. There are no special storage instructions for this medicine. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Angeliq contains

The active substances of Angeliq are estradiol (as estradiol hemihydrate) and drospirenone; each tablet contains 1 mg of estradiol and 2 mg of drospirenone. The other ingredients of Angeliq are: Core: lactose monohydrate, corn starch, pregelatinized corn starch, povidone, magnesium stearate (E470b). Coating: hypromellose (E464), macrogol 6000, talc (E553b), titanium dioxide (E171), and iron oxide red (E172).

What Angeliq looks like and contents of the pack

Angeliq tablets are red, round, biconvex, and film-coated. On one side of the tablet, in a regular hexagon, are the letters DL. The blister pack contains 28 tablets. The blister pack is marked with the days of the week. Packs containing one or three blister packs are available.

Marketing authorization holder

Bayer AG Kaiser-Wilhelm-Allee 1 51373 Leverkusen Germany

Manufacturer

Bayer AG Müllerstrasse 178 13353 Berlin Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Angeliq - Belgium, Croatia, Czech Republic, Estonia, Germany, Finland, France, Ireland, Italy, Lithuania, Latvia, Luxembourg, Malta, Netherlands, Poland, Portugal, Slovenia, Spain For more information, consult a doctor or the representative of the marketing authorization holder: Bayer Sp. z o.o. Al. Jerozolimskie 158 02-326 Warszawa tel. 0 22 572 35 00

Date of last revision of the leaflet: 01/2024