Angeliq

Patient Information Leaflet

Angeliq, 1 mg + 2 mg, film-coated tablets
Estradiol + Drospirenone
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• 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 personally. 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 any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Angeliq is and what it is used for
2. What you need to know 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 Angeliq is and what it is used for

Angeliq is a medicine used in Hormone Replacement Therapy (HRT). It contains two types of female hormones: an estrogen and a progestagen. Angeliq is used in postmenopausal women who have been at least one year since their last menstrual period.

Angeliq is used for:

Relief of postmenopausal symptoms
During menopause, the amount of estrogen produced by a woman's body decreases. This may cause symptoms such as sudden feelings of heat in the face, neck and chest (hot flushes). Angeliq relieves these postmenopausal symptoms. Angeliq will be prescribed when symptoms significantly interfere with your daily life.

Prevention of osteoporosis
After menopause, some women may develop brittle bones (osteoporosis). Please discuss all available treatment options with your doctor. Angeliq may be used to prevent postmenopausal osteoporosis in women at high risk of future fractures, when other treatments are not suitable.

2. Important information before using Angeliq

Medical history and regular medical examinations
Hormone replacement therapy (HRT) carries risks that should be considered when deciding whether to start or continue treatment.
Experience with treating women with premature menopause (due to ovarian failure or surgical removal of ovaries) is limited. In women with premature menopause, the risks associated with HRT may differ. In such cases, consult your doctor.
Before starting (or restarting) HRT, your doctor will take a detailed medical history of you and your family. The doctor may decide whether a physical examination is necessary. The doctor may examine your breasts and (or), if necessary, perform a gynecological examination.
After starting Angeliq, you should have regular medical check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Angeliq treatment.
You should regularly examine your breasts, as recommended by your doctor.

When not to use Angeliq:
Do not use Angeliq if any of the following conditions apply to you. If you are unsure whether any of the listed conditions apply to you, you should consult your doctor before using Angeliq.
Do not use Angeliq:

• if you have or have previously had breast cancer, or if breast cancer is suspected
• if you have an estrogen-sensitive tumour, such as cancer of the endometrium (lining of the womb), or if such a tumour is suspected
• if you have unexplained vaginal bleeding
• if you have excessive thickening of the endometrium (endometrial hyperplasia)
• if you have or have previously had a blood clot in a vein (venous thrombosis), for example in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism)
• if you have a known predisposition to blood clots (such as protein C, protein S or antithrombin deficiency)
• if you have or have recently had an arterial disease caused by blood clots, such as heart attack, stroke or angina pectoris
• if you have or have previously had liver disease and liver function tests have not returned to normal
• if you have a rare inherited blood pigment disorder called "porphyria"
• if you have severe kidney disease or acute renal failure
• if you are allergic (hypersensitive) to estrogens, progestogens or any of the other ingredients of Angeliq (listed in section 6).
  • If any of the above symptoms occur while taking Angeliq, stop using the medicine immediately and contact your doctor.

Warnings and precautions
Talk to your doctor or pharmacist before starting Angeliq. If you have ever had any of the conditions described below, inform your doctor before starting treatment, as these conditions may recur or worsen during Angeliq treatment. In such cases, more frequent check-ups with your doctor are recommended:

• fibroids in the uterus
• endometriosis (growth of endometrial tissue outside the uterus) or past history of endometrial hyperplasia
• increased risk of venous thrombosis (see below "Blood clots in veins (thrombosis)")
• increased risk of developing estrogen-sensitive cancers (such as breast cancer in mother, sister or grandmother)
• high blood pressure
• liver disease, such as benign liver tumour
• diabetes
• gallstones
• migraine or severe headaches
• autoimmune disease that may affect multiple organs (systemic lupus erythematosus, SLE)
• epilepsy
• asthma
• ear and hearing disorder (otosclerosis)
• very high levels of blood fats (triglycerides)
• fluid retention associated with heart or kidney failure
• hereditary or acquired angioedema.

You should stop taking Angeliq and contact your doctor immediately
if you notice any of the following symptoms during HRT:

• any of the conditions listed in section "When not to use Angeliq"
• 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 combined with breathing difficulties, suggesting angioedema
• significant increase in blood pressure (symptoms may include: headache, fatigue, dizziness)
• occurrence of new migraine-like headaches
• pregnancy
• symptoms suggesting 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 section "Blood clots in veins (thrombosis)".
  Note: Angeliq is not a contraceptive. Women who have not yet reached 12 months since their last menstrual period or who are under 50 years of age may still require additional contraception to prevent pregnancy. Consult your doctor for advice.

HRT and cancer
Excessive thickening of the endometrium (endometrial hyperplasia) and cancer of the endometrium (endometrial cancer)
Taking estrogen-only HRT increases the risk of excessive thickening of the endometrium (endometrial hyperplasia) and cancer of the endometrium (endometrial cancer). The progestogen in Angeliq protects against this additional risk.

Irregular bleeding
Irregular bleeding or spotting may occur during the first 3–6 months of taking Angeliq. However, if irregular bleeding:

• continues after the first 6 months of treatment
• occurs after a break of more than 6 months since starting Angeliq
• continues after stopping Angeliq
  you should contact your doctor as soon as possible.

Breast cancer
Evidence confirms that using hormone replacement therapy (HRT), either estrogen combined with progestogen or estrogen alone, increases the risk of developing breast cancer – this risk depends on the duration of treatment. The increased risk becomes apparent after 3 years of HRT use. After stopping HRT, the additional risk gradually decreases, but may persist for 10 years or longer if HRT was used for more than 5 years.
Comparison:
Among women aged 50 to 54 who do not use HRT, breast cancer will be diagnosed in an average of 13 to 17 per 1000 women over a 5-year period.
Among women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16–17 per 1000 women (i.e. 0 to 3 additional cases).
Among women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 per 1000 women (i.e. 4 to 8 additional cases).
Among women aged 50 to 59 who do not use HRT, breast cancer will be diagnosed in an average of 27 per 1000 women over a 10-year period.
Among women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 per 1000 women (i.e. 7 additional cases).
Among women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 per 1000 women (i.e. 21 additional cases).

• You should regularly examine your breasts. If any of the following changes occur, contact your doctor:
  • skin indentation or dimpling
  • changes in the nipple
  • any noticeable or palpable lumps.

Additionally, participation in screening mammography is recommended if available. When undergoing screening mammography, inform the nurse or radiology staff that you are using HRT, as this medicine may increase breast density, which can affect mammography results. With increased breast density, mammography may not detect all lumps.

Ovarian cancer
Ovarian cancer is rare – significantly less common than breast cancer. Using 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, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 per 2000 women over a 5-year period.
Among women using HRT for 5 years, ovarian cancer will occur in about 3 per 2000 women (i.e. about 1 additional case).

Effects of HRT on the heart and circulation
Blood clots in veins (thrombosis)
The risk of venous blood clots is about 1.3 to 3 times higher in women using HRT, especially during the first year of treatment, compared to women not using HRT.
Blood clots can be dangerous, particularly if one travels to the lungs, causing chest pain, shortness of breath, fainting or even death.
The risk of developing a blood clot increases with age and if any of the following conditions apply to you. Inform your doctor:

• if you are unable to walk for a prolonged period due to major surgery, injury or illness (see also section 3 "Before surgery")
• if you are very overweight (BMI > 30 kg/m²)
• if you have blood clotting disorders requiring long-term anticoagulant therapy
• if close relatives have previously had blood clots in the legs, lungs or other organs
• if you have systemic lupus erythematosus (SLE)
• if you have cancer.

Symptoms suggesting a blood clot are listed in the section "Stop taking Angeliq and contact your doctor immediately".
Comparison:
Among women aged about 50 not using HRT, about 4 to 7 per 1000 women can be expected to develop a venous blood clot over a 5-year period.
Among women aged about 50 using combined estrogen-progestogen HRT for more than 5 years, 9 to 12 such cases per 1000 women will occur (i.e. 5 additional cases).

Heart disease (heart attack)
HRT has not been shown to prevent heart attacks.
In women over 60 years of age using combined estrogen-progestogen HRT, the risk of heart disease is slightly higher than in women not using HRT.

Stroke
The risk of stroke in women using HRT is about 1.5 times higher than in women not using HRT. The number of additional stroke cases related to HRT use increases with age.
Comparison:
Among women aged about 50 not using HRT, about 8 per 1000 women are expected to have a stroke over a 5-year period. Among women aged about 50 using HRT, this number is 11 per 1000 women over 5 years (i.e. 3 additional cases).

Other diseases

• HRT does not prevent memory loss. Some evidence suggests greater memory loss in women who start HRT after age 65. For more information, speak with your doctor.
• If you have kidney function disorders and elevated serum potassium levels, especially if you are taking medications that increase potassium, your doctor may check your blood potassium levels during the first month of treatment.
• If you have high blood pressure, taking Angeliq may lower it. Do not use Angeliq to treat high blood pressure.
• If you are prone to pigmentation spots (melasma) on the face, avoid exposure to sunlight or ultraviolet rays while taking Angeliq.

Angeliq and other medicines
Tell your doctor or pharmacist about all medicines you are currently using, have recently used or plan to use. Some medicines (listed below) may affect the action of Angeliq, possibly leading 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 infections (so-called 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 conditions and 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 seizure frequency
• medicines used to treat hepatitis C virus (HCV) (such as treatment regimens with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir), as they may cause increased liver function parameters in blood tests (elevated liver enzyme AlAT activity) in women using combined hormonal contraceptives containing ethinylestradiol. Angeliq contains estradiol instead of ethinylestradiol. It is unknown whether elevated AlAT liver enzyme activity may occur when Angeliq is used concurrently with such HCV combination therapies.

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

• medicines used to treat:
• inflammation or pain (e.g. acetylsalicylic acid, ibuprofen)
• certain types of heart disease or high blood pressure, e.g. diuretics (water tablets), ACE inhibitors (e.g. enalapril) or angiotensin II receptor antagonists (e.g. losartan).
  If you are taking blood pressure-lowering medicines and Angeliq, the result may be an additional decrease in blood pressure.

Tell your doctor or pharmacist about all medicines you are currently or recently taking, including over-the-counter medicines, herbal medicines and other natural remedies.
Your doctor will provide appropriate advice.

Laboratory tests
If blood tests are required, inform your doctor or nurse that you are taking Angeliq, as this medicine may affect the results of certain tests.

Pregnancy and breastfeeding
Angeliq is intended for postmenopausal women.
If you become pregnant, stop taking Angeliq 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 you have been previously diagnosed with intolerance to certain sugars, you should consult your doctor before taking this medicine.

3. How to use Angeliq

This medicine should always be taken exactly as directed by the doctor. If in doubt, consult a
doctor or pharmacist. The doctor will decide how long Angeliq should be taken.
One tablet should be taken daily, preferably at the same time each day. Swallow the tablet whole
with water. Angeliq may be taken with or without food. A new pack should be started the day
after finishing the previous pack.
Do not make a break between packs.
If the patient is currently using another HRT medicine: continue taking the current
HRT medicine until all tablets in the pack have been taken and the monthly course is completed.
The first tablet of Angeliq should be taken the following day. Do not make a break between the
previously used HRT medicine and Angeliq.
When starting HRT for the first time: Angeliq may be started on any day.
Taking more Angeliq than recommended
Overdose may cause nausea, vomiting, and irregular bleeding. Specific treatment is not usually
required, but if in doubt, consult a doctor.
If a dose of Angeliq is missed
If a patient forgets to take a tablet at the usual time and the delay is less than 24 hours, take the
tablet 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 each day. Do not take a double dose to make up for a missed
tablet.
If a patient forgets to take tablets for several days, irregular bleeding may occur.
Stopping Angeliq
Typical menopausal symptoms may occur, including hot flushes, sleep disturbances, nervousness,
dizziness, or vaginal dryness. Bone density loss may begin after stopping Angeliq. If a patient
wishes to discontinue Angeliq, this should be discussed with a doctor or pharmacist. If there are
any further doubts regarding the use of this medicine, consult a doctor or pharmacist.
In case of surgery
If a patient is scheduled for surgery, she should inform the surgeon about taking Angeliq. It may
be necessary to stop taking Angeliq approximately 4–6 weeks before the planned operation to
reduce the risk of blood clots (see section 2, "Venous thrombosis"). Ask the doctor when it is safe
to resume taking Angeliq.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although they do not occur in everyone.
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 womb (endometrial hyperplasia or endometrial cancer)
• ovarian cancer
• blood clots in the legs or lungs (venous thromboembolism)
• heart disease
• stroke
• possible memory loss if HRT is started after the age of 65

Detailed information about these adverse effects is provided in section 2.

Like any medicine, Angeliq can cause adverse effects, although they do not occur in everyone.
Below are adverse effects that have been associated with the use of Angeliq:

Very common adverse effects (occur in at least 1 out of every 10 patients):

• unexpected bleeding similar to menstrual periods (see also section 2 "HRT and cancer")
• breast tenderness
• breast pain

Unexpected bleeding similar to menstrual periods may occur during the first few months of treatment with Angeliq. Such bleeding is usually transient and resolves during continued treatment. If it does not, you should consult your doctor.

Common adverse effects (occur in 1 to 10 out of every 100 patients):

• depression, mood changes, nervousness
• headache
• abdominal pain, nausea, abdominal distension
• breast nodules (benign breast tumours), breast swelling
• enlargement of uterine fibroids
• non-cancerous cervical cell proliferation
• irregular vaginal bleeding
• vaginal discharge
• weakness, localized fluid retention

Uncommon adverse effects (occur in 1 to 10 out of every 1,000 patients):

• weight gain or loss, loss or increased appetite, increased blood lipid levels
• sleep disturbances, anxiety, decreased libido
• burning or prickling sensations, reduced concentration, dizziness
• eye problems (e.g. bloodshot eyes), visual disturbances (e.g. blurred vision)
• palpitations
• embolism, venous thrombosis (see also section 2 "Blood clots in veins (thrombosis)"), high blood pressure, migraine, phlebitis, varicose veins
• shortness of breath
• gastrointestinal disturbances, diarrhoea, constipation, vomiting, dry mouth, bloating, taste disturbances
• changes in liver enzyme activity (seen in blood laboratory tests)
• skin problems, acne, hair loss, itching, excessive hair growth
• back pain, joint pain, limb pain, muscle cramps
• urinary tract disorders and infections
• breast cancer, endometrial hyperplasia, benign uterine tumour, vaginal candidiasis, vaginal dryness and itching
• breast nodules (mastopathy), ovarian, cervical and uterine disorders, pelvic pain
• generalized fluid retention, chest pain, malaise, increased sweating

Rare adverse effects (occur in 1 to 10 out of every 10,000 patients):

• anaemia
• dizziness
• tinnitus (ringing in the ears)
• gallstones
• muscle pain
• salpingitis (inflammation of the fallopian tubes)
• milky discharge from the nipples
• chills

During clinical trials, the following adverse effects occurred in women with high blood pressure:

• increased potassium levels (hyperkalaemia), which may sometimes lead to muscle cramps, diarrhoea, nausea, dizziness or headache
• heart failure, enlarged heart, palpitations, cardiac rhythm disturbances
• increased blood aldosterone levels

When other HRT medicines were used, the following adverse effects were observed:

• gallbladder disorders
• various skin disorders:
  • skin discolouration, especially on the face or neck, known as "pregnancy mask" (chloasma)
  • painful red skin nodules (erythema nodosum)
  • rash with target-like redness or ulceration (erythema multiforme)

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C,
02-222 Warsaw,
Tel.: +48 22 4921301,
Fax: +48 22 4921309,
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to 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 outer carton and blister pack.
The expiry date refers to the last day of the stated month.
There are no special storage requirements for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. Such measures help protect the environment.

6. Contents of the pack and other information

What Angeliq contains
The active substances in this medicine are estradiol (in the form of estradiol hemihydrate) and drospirenone; each tablet contains 1 mg of estradiol and 2 mg of drospirenone.
Other components of the medicine are:
Core: monohydrate lactose, corn starch, pregelatinized corn starch, povidone, magnesium stearate (E470b).
Coating: hypromellose (E464), macrogol 6000, talc (E553b), titanium dioxide (E171) and red iron oxide (E172).
What Angeliq looks like and contents of the pack
Angeliq tablets are red, round, biconvex, film-coated. On one side of the tablet, within a regular hexagon, are the letters DL.
Each blister contains 28 tablets. The blister is marked with days of the week. Packs containing one or three blisters are available.
Marketing Authorisation Holder
Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen
Germany
Manufacturer:
Bayer AG
Müllerstrasse 178
13353 Berlin
Germany
This medicinal product is authorised in the European Economic Area countries 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 further information, please contact the Marketing Authorisation Holder's representative:
Bayer Sp. z o.o.
Al. Jerozolimskie 158
02-326 Warsaw
tel. 0 22 572 35 00