Package leaflet: Information for the user

A 1 mg / 2 mg film-coated tablets
Estradiol / Drospirenone
Please read all of this leaflet carefully before you start 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 only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Angeliq is and what it is used for
What you need to know before taking Angeliq
➢ Medical examination and regular check-ups
➢ Do not take Angeliq
➢ Warnings and precautions
➢ HRT and cancer
➢ Effects of HRT on the heart and circulation
➢ Other conditions
➢ Other medicines and Angeliq
➢ Laboratory tests
➢ Pregnancy and breastfeeding
➢ Driving and use of machines
➢ Angeliq contains lactose
How to take Angeliq
➢ If you take more Angeliq than you should
➢ If you forget to take Angeliq
➢ If you stop taking Angeliq
➢ If you are due to undergo surgery
Possible side effects
How to store Angeliq
Contents of the pack and other information

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Note: this index applies only to the "booklet" format of Angeliq; in the "leaflet" format, the index contains only the main headings from 1 to 6:

What Angeliq is and what it is used for
What you need to know before taking Angeliq
How to take Angeliq
Possible side effects
How to store Angeliq
Contents of the pack and other information

1. What Angeliq is and what it is used for

Angeliq is a Hormone Replacement Therapy (HRT). It contains two types of female hormones, an oestrogen and a progestogen.
Angeliq is used in postmenopausal women who have been at least 1 year since their last natural menstrual period.
Angeliq is used for:
Relief of postmenopausal symptoms
During menopause, the amount of oestrogen produced by a woman's body decreases. This can cause symptoms such as warmth in the face, neck and chest ("hot flushes"). Angeliq relieves these symptoms after menopause. Angeliq will be prescribed if your symptoms seriously impair your daily life.
Prevention of osteoporosis
After menopause, some women may develop weak and brittle bones (osteoporosis). You should discuss all available options with your doctor.
If you are at high risk of fractures due to osteoporosis and cannot take other medicines, you may use Angeliq for the prevention of postmenopausal osteoporosis.

2. What you should know before taking Angeliq

Medical examination and regular check-ups
Hormone replacement therapy (HRT) carries certain risks that must be considered when deciding whether to start or continue treatment.
Experience with treating women who have early menopause (due to cessation of ovulation or surgical intervention) is limited. If you have early menopause, the risks associated with HRT may differ. Consult your doctor.
Before starting (or restarting) HRT, your doctor will ask you questions about your personal and family medical history. Your doctor may decide to perform certain tests. These may include a breast examination and/or a pelvic examination if necessary.
Once you have started treatment with Angeliq, you should visit your doctor regularly (at least once a year). During these check-ups, you and your doctor will discuss the benefits and risks of continuing treatment with Angeliq.
Have regular breast examinations as recommended by your doctor.
Do not take Angeliq
if any of the following conditions apply to you. If you are unsure about any of the conditions listed below, consult your doctor before taking Angeliq.
Do not take Angeliq
➢ If you have or have ever had breast cancer, or if you suspect you may have it
➢ If you have a cancer sensitive to estrogens, such as cancer of the uterine lining (endometrium), or if you suspect you may have it
➢ If you have any unexplained vaginal bleeding
➢ If you have excessive thickening of the uterine lining (endometrial hyperplasia)
➢ If you have or have ever had a blood clot in a vein (venous thrombosis), such as in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism)
➢ If you have blood clotting disorders (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, stroke or angina
➢ If you have or have had liver disease and your liver function tests have not returned to normal
➢ If you have a rare inherited disease called “porphyria”

➢ If you have severe kidney disease or acute renal failure
➢ If you are allergic (hypersensitive) to estrogens, progestogens, or any of the excipients of Angeliq (listed in section 6).
If any of the above conditions develops for the first time while you are taking Angeliq, stop treatment immediately and consult your doctor without delay.
Warnings and precautions
Talk to your doctor or pharmacist before taking Angeliq. Inform your doctor if you have ever had any of the following conditions before starting treatment, as they may recur or worsen during treatment with Angeliq. In such cases, you should visit your doctor more frequently for check-ups:
➢ fibroids in the uterus
➢ endometriosis (growth of uterine lining tissue outside the uterus) or history of excessive growth of the uterine lining (endometrial hyperplasia)
➢ increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”)
➢ increased risk of estrogen-sensitive breast cancer (mother, sister or grandmother with breast cancer)
➢ high blood pressure
➢ liver disease such as benign liver tumor
➢ diabetes
➢ gallstones
➢ migraine or severe headaches
➢ an autoimmune disease affecting multiple organs (systemic lupus erythematosus (SLE))
➢ epilepsy
➢ asthma
➢ a disease affecting the eardrum and hearing (otosclerosis)
➢ very high levels of fats in the blood (triglycerides)
➢ fluid retention due to heart or kidney problems
➢ hereditary or acquired angioedema.
Stop taking Angeliq and consult your doctor immediately
if you experience any of the following conditions while taking HRT:
➢ any condition listed under “Do not take Angeliq”
➢ yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease
➢ swelling of the face, tongue and/or throat and/or difficulty swallowing or hives with breathing difficulties, which are indicative of angioedema
➢ marked increase in blood pressure (symptoms may include headache, fatigue, dizziness)
➢ new-onset migraine-type headache
➢ pregnancy
➢ if you notice signs of a blood clot such as

painful swelling and redness of the legs
sudden chest pain
difficulty breathing For further information, see section “Blood clots in a vein (thrombosis)”

Note: Angeliq is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, you may still need to use additional contraceptive measures to prevent pregnancy. Ask your doctor for advice.

HRT and cancer
Excessive thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial carcinoma)
Taking estrogen-only HRT increases the risk of thickening of the uterine lining (endometrial hyperplasia) and cancer of the uterine lining (endometrial carcinoma). The presence of a progestogen in Angeliq protects you from 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 beyond the first 6 months
occurs after you have been taking Angeliq for more than 6 months
continues after stopping Angeliq, see your doctor as soon as possible.

Breast cancer
Evidence shows that taking combined estrogen-progestogen HRT or estrogen-only HRT increases the risk of breast cancer. The additional risk depends on the duration of HRT use. This additional risk becomes apparent within 3 years of use. After stopping HRT, the additional risk decreases over time, but may persist for 10 years or more if HRT has been used for more than 5 years.
Comparison
Among women aged 50–54 years not taking HRT, breast cancer will be diagnosed in an average of about 13–17 out of 1,000 women over a 5-year period. Among women aged 50 who start taking estrogen-only HRT for 5 years, there will be 16–17 cases per 1,000 users (i.e., 0–3 additional cases). Among women aged 50 who start taking combined estrogen-progestogen HRT for 5 years, there will be 21 cases per 1,000 treated women (i.e., 4–8 additional cases).
Among women aged 50–59 years not taking HRT, breast cancer will be diagnosed in an average of 27 out of 1,000 women over a 10-year period.
Among women aged 50 who start taking estrogen-only HRT for 10 years, there will be 34 cases per 1,000 users (i.e., 7 additional cases).
Among 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).
➢ Examine your breasts regularly. Make an appointment with your doctor if you notice any changes such as:

skin dimpling or puckering;
changes in the nipples;
any visible or palpable lumps.

In addition, you are advised to participate in mammographic screening programs when offered. For mammographic screening, it is important that you inform the nurse/healthcare professional performing the X-ray that you are using HRT, as this treatment may increase breast density, which could affect the mammogram result. When breast density is increased, a mammogram may not detect all lumps.
Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer.

The use of estrogen-only or combined estrogen-progestogen therapy has been associated with a slight increase in the risk of ovarian cancer. The risk of ovarian cancer varies with age. For example, among women aged 50–54 years not taking HRT, about 2 out of 2,000 women will be diagnosed with ovarian cancer within 5 years. For women taking HRT for 5 years, there will be about 3 cases per 2,000 treated women (i.e., about 1 additional case).
Effects of HRT on the heart and circulation
Blood clots in a vein (thrombosis)
HRT can increase the risk of blood clots in veins by 1.3 to 3 times, especially during the first year of use.
Blood clots can be dangerous; if they travel to the lungs, they can cause chest pain, sudden shortness of breath, collapse, or even death.
The risk of developing a blood clot in a vein increases with age and if any of the following conditions apply to you. Inform your doctor if any of the following apply to you:

you are unable to walk for long periods due to major surgery, accident or illness (see also section 4, “If you are undergoing surgery”)
you are severely overweight (BMI > 30 kg/m²)
you have a blood clotting disorder requiring long-term treatment with a blood-thinning medicine
a close relative has had a blood clot in the leg, lung or another organ
you have systemic lupus erythematosus (SLE)
you have cancer

For possible signs of a blood clot, see “Stop taking Angeliq and contact your doctor immediately”
Comparison
For women around 50 years of age not taking HRT, on average, 4–7 out of 1,000 women are expected to develop a blood clot in a vein over a 5-year period. For women around 50 years of age taking combined estrogen-progestogen HRT for more than 5 years, there will be 9–12 cases per 1,000 users (i.e., an increase of 5 cases).
Heart disease (heart attack)
There is no evidence that HRT prevents heart disease.
Women over 60 years of age who use combined estrogen-progestogen HRT have a slightly higher chance of developing heart disease compared to women not using HRT.
Stroke
The risk of stroke is about 1.5 times higher in users of HRT than in non-users.
The number of additional stroke cases due to HRT use increases with age.
Comparison
For women around 50 years of age not taking HRT, on average, 8 out of 1,000 women may have a stroke over a 5-year period. For women around 50 years of age taking combined estrogen-progestogen HRT for more than 5 years, there will be 11 cases per 1,000 users (i.e., an increase of 3 cases).

Other conditions

HRT does not prevent memory loss. The risk of memory loss may be higher in women who start using HRT after age 65. Consult your doctor.
If you have kidney disease and elevated serum potassium levels, especially if you are taking other medicines that increase serum potassium, your doctor may monitor your blood potassium levels during the first month of treatment.
If you have high blood pressure, treatment with Angeliq may lower it. Angeliq should not be used to treat high blood pressure.
If you are prone to developing skin discoloration patches (melasma), avoid exposure to sunlight or ultraviolet light while taking Angeliq.

Other medicines and Angeliq
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Some medicines may interfere with the effects of Angeliq and cause irregular bleeding. These include:

medicines for epilepsy (e.g., barbiturates, phenytoin, primidone, carbamazepine, oxcarbazepine, topiramate and felbamate)
medicines for tuberculosis (e.g., rifampicin and rifabutin)
medicines for HIV and hepatitis C virus infections (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as nevirapine, efavirenz, nelfinavir and ritonavir)
the herbal remedy St. John’s wort (Hypericum perforatum)
medicines for the treatment of fungal infections (such as griseofulvin, itraconazole, ketoconazole, voriconazole, fluconazole)
medicines for the treatment of bacterial infections (such as clarithromycin, erythromycin)
medicines for the treatment of certain heart conditions, high blood pressure (such as verapamil, diltiazem)
Grapefruit juice

HRT may interfere with the effects of other medicines:

an epilepsy medicine (lamotrigine), as it may increase the frequency of seizures;
medicines for hepatitis C virus (HCV) (such as combination regimens with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir) may cause increases in blood test results related to liver function (increase in liver enzyme ALT) in women using COCs containing ethinylestradiol. Angeliq contains estradiol instead of ethinylestradiol. It is not known whether an increase in liver enzyme ALT may occur when Angeliq is used with these HCV combination regimens.

The following medicines may cause small increases in serum potassium:

medicines used to treat:
inflammation or pain (e.g., aspirin, ibuprofen);
certain types of heart disease or hypertension (e.g., diuretics, ACE inhibitors (e.g., enalapril), angiotensin II receptor antagonists (e.g., losartan). If you are being treated for hypertension and take Angeliq, a further reduction in blood pressure may occur.

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
including over-the-counter medicines, herbal remedies or other natural products.
Your doctor will provide you with the necessary instructions.
Laboratory tests

If you need a blood test, inform your doctor or laboratory staff that you are taking Angeliq, as this medicine may affect the results of certain tests.
Pregnancy and breastfeeding
Angeliq is intended for use in postmenopausal women.
If you become pregnant, stop taking Angeliq immediately and contact your doctor.
Driving and using machines
There is no reason to believe that the use of Angeliq affects the ability to drive or operate machinery.
Angeliq contains lactose
Angeliq contains lactose (a type of sugar).
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Angeliq

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist. Your doctor will decide how long you should take Angeliq.
Take one tablet daily, preferably at the same time each day. Swallow the tablet whole with a little water. You may take Angeliq with or without food. Start the next pack of tablets the day after finishing the current pack.
Do not interrupt treatment between packs.

If you are currently taking other HRT preparations: Continue until you have finished your current pack and taken all the tablets for that month. Take the first Angeliq tablet the following day. Do not leave a gap between the old tablets and Angeliq tablets.

If this is your first HRT treatment: You may start taking Angeliq tablets on any day.

If you take more Angeliq than you should
Overdose may cause nausea, vomiting, and irregular bleeding. Specific treatment is not required, but if you are concerned, consult your doctor.

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

If you stop taking Angeliq
You may start experiencing again typical menopausal symptoms, which may include hot flushes, sleep disturbances, nervousness, dizziness, or vaginal dryness. Discontinuing Angeliq will also lead to loss of bone mass. If you wish to stop treatment with Angeliq, consult your doctor or pharmacist. If you have any questions about using this medicine, consult your doctor or pharmacist.

If you need to undergo surgery
If you have planned surgery, inform your surgeon that you are taking Angeliq. It may be necessary to stop taking Angeliq approximately 4–6 weeks before the operation to reduce the risk of thrombosis (see also section 2 “Blood clots in a vein”). Ask your doctor when you can restart taking Angeliq.

4. Possible side effects

Like all medicines, Angeliq can cause side effects, although not everybody gets them. Women using HRT have a slightly increased risk of developing the following conditions compared to non-users:

breast cancer
excessive growth or cancer of the lining of the womb (endometrial hyperplasia or 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.

For more information about these side effects, see section 2.
Like all medicines, Angeliq can cause side effects, although not everybody gets them. The following side effects have been reported with the use of Angeliq.

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

unexpected menstrual-like bleeding (see also section 2 “HRT and cancer”)
breast tenderness
breast pain

Unexpected menstrual-like bleeding may occur during the first months of treatment with Angeliq. Usually, this is temporary and normally resolves with continued treatment. If it does not, contact your doctor.

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

depression, mood changes, nervousness
headache
stomach discomfort, nausea, stomach bloating
breast lumps (benign breast neoplasm), breast swelling
increase in size of uterine fibroids
non-cancerous growth of cells in the cervix (benign cervical growth)
irregular vaginal bleeding
vaginal discharge
loss of energy, localized fluid retention

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

weight gain or loss, loss or increase in appetite, increased blood fats
sleep disorders, anxiety, decreased sexual interest
burning or prickling sensation, decreased concentration, dizziness
eye problems (e.g. red eyes), vision disturbances (e.g. blurred vision)
palpitations

thrombosis, venous thrombosis (see also section 2 “Blood clots in a vein (thrombosis)”), high blood pressure, migraine, inflammation of veins, varicose veins
shortness of breath
stomach discomfort, diarrhea, constipation, vomiting, dry mouth, flatulence, taste disturbances
altered liver enzymes (detectable in blood tests)
skin problems, acne, hair loss, skin itching, hirsutism
back pain, joint pain, limb pain, muscle cramps
urinary tract disorders and infections
breast cancer, thickening of the uterine lining, unusual benign growth in the uterus, candidiasis, vaginal dryness and itching
breast lumps (fibrocystic mastopathy), disorders of the ovaries, cervix, and uterus, pelvic pain
generalized fluid retention, chest pain, general malaise, increased sweating

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

anaemia
vertigo
tinnitus (ringing in the ears)
gallstones
muscle pain
inflammation of the fallopian tubes
milk secretion from the nipples
chills

The following side effects occurred in clinical studies in women with high blood pressure:

high potassium levels (hyperkalaemia), sometimes causing muscle cramps, diarrhoea, nausea, dizziness, or headache
heart failure, heart enlargement, rapid heartbeat, effects on heart rhythm
increased blood aldosterone levels

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

gallbladder disease
various skin disorders:
skin discoloration, especially on the face or neck, known as “pregnancy mask” (chloasma)
red, painful skin nodules (erythema nodosum)
skin rash with target-like lesions or ulcers (erythema multiforme)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
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 which is stated on the packaging and on the blister after
"EXP". The expiry date refers to the last day of that month.

Angeliq does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

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

Description of the appearance of Angeliq and package contents
Angeliq tablets are film-coated, red, round, convex tablets. One side is marked with the letters "DL" within a regular hexagon.
They are available in blisters containing 28 tablets, with the days of the week printed on the blister.
Angeliq is available in packages containing 1 or 3 blisters.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Bayer S.p.A. - Viale Certosa, 130 - 20156, Milan (MI), Italy

Manufacturer
Bayer AG, Muellerstrasse 178 – 13353 Berlin, Germany

This medicinal product is authorized 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, the Netherlands, Poland, Portugal, Slovenia, Spain.

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