Package leaflet: Information for the user

PAOSONELLE

1 mg/2 mg film-coated tablets
estradiol/drospirenone
Equivalent medicine
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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

What PAOSONELLE 1 mg/2 mg film-coated tablets (hereinafter PAOSONELLE) is and what it is used for
What you need to know before taking PAOSONELLE
How to take PAOSONELLE
Possible side effects
How to store PAOSONELLE
Contents of the pack and other information

1. What PAOSONELLE is and what it is used for

PAOSONELLE is a Hormone Replacement Therapy (HRT). It contains two types of female hormones, an
estrogen and a progestogen. PAOSONELLE is used in postmenopausal women who have
completed at least 12 months (1 year) since their last natural menstrual period.
What PAOSONELLE is used for
Relief of symptoms occurring after menopause
During menopause, the amount of estrogen produced by a woman's body decreases. This may
cause symptoms such as heat sensations in the face, neck and chest ("hot flushes"). PAOSONELLE relieves
these symptoms after menopause. PAOSONELLE will be prescribed if your symptoms severely affect
your daily life.
Prevention of osteoporosis
After menopause, some women may develop weak 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 medications, you may use
PAOSONELLE for the prevention of postmenopausal osteoporosis.

2. What you should know before taking PAOSONELLE

Medical examination and regular check-ups
The use of HRT carries risks that must be considered when deciding whether to start or continue treatment.
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Experience with treating women who have experienced early menopause (due to cessation of ovulation or surgical intervention) is limited. If you have early menopause, the risks associated with using HRT may differ. Consult your doctor.
Before starting (or restarting) HRT, your doctor will ask you questions about your personal medical history and that of your family. The doctor may decide to perform certain tests.
These may include a breast examination and/or an internal examination if necessary.
Once you have started treatment with PAOSONELLE, you should visit your doctor for regular check-ups (at least once a year). During these visits, you will discuss with your doctor the benefits and risks associated with continuing treatment with PAOSONELLE.
Have regular breast examinations, as recommended by your doctor.
Do not take PAOSONELLE
if any of the conditions listed below apply to you. If you are unsure about any of the conditions described below, consult your doctor before taking PAOSONELLE.
Do not take PAOSONELLE

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) that is untreated
if you have or have ever had a blood clot in a vein (thrombosis), such as in the legs (deep vein thrombosis) or lungs (pulmonary embolism)
if you have disorders related to blood clotting (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
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”, a hereditary condition
if you have severe kidney disease or acute renal failure
if you are allergic (hypersensitive) to estrogens, progestogens or any of the excipients of PAOSONELLE (listed in section 6)
if you are allergic to peanuts or soy.

If any of the above conditions occur for the first time while you are taking PAOSONELLE, stop treatment immediately and consult your doctor without delay.
Warnings and precautions
Talk to your doctor or pharmacist before taking PAOSONELLE.
Inform your doctor if you have ever had any of the following conditions before starting treatment, as these conditions may recur or worsen during treatment with PAOSONELLE. If this occurs, you should see your doctor more frequently for check-ups:

fibroids within the uterus
growth of uterine tissue in other locations (endometriosis) 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 2/10
liver disease such as a benign liver tumor
diabetes
gallstones
migraine or severe headaches
an autoimmune disease affecting multiple organs (systemic lupus erythematosus (SLE))
epilepsy
asthma
a condition 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 PAOSONELLE and consult your doctor immediately
if you experience any of the following conditions while taking HRT:

any condition listed in the section “Do not take PAOSONELLE”
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, together 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 in the legs
sudden chest pain
difficulty breathing. For further information, see section “Blood clots in a vein (thrombosis)”.

Note: PAOSONELLE 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. Consult your doctor.
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 PAOSONELLE protects you from this additional risk.
Irregular bleeding
You may experience irregular bleeding or spotting during the first 3–6 months of taking PAOSONELLE.
However, if irregular bleeding:

continues beyond the first 6 months
occurs after you have been taking PAOSONELLE for more than 6 months
continues after stopping PAOSONELLE, 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 appears within 3 years of use. After stopping HRT, the additional risk will gradually decrease over time, but may persist for 10 years or more if HRT has been used for more than 5 years.
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Comparison
Among women aged 50 to 54 years not taking HRT, breast cancer will be diagnosed in approximately 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 to 59 years not taking HRT, breast cancer will be diagnosed in approximately 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).
Regularly check your breasts. Make an appointment with your doctor if you notice any changes such as:

skin indentations
changes in the nipples
any visible or palpable lumps.

Additionally, 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 results. Where breast density is increased, mammography 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 to 54 years not taking HRT, about 2 out of 2,000 women will receive an ovarian cancer diagnosis 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, and if they reach 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:

you are unable to walk for long periods due to major surgery, accident or illness (see also section 3, “If you need to undergo surgery”)
you are severely overweight (BMI > 30 kg/m²)
you have any blood clotting disorder requiring long-term treatment with a medicine that prevents blood clots
if a close relative has had a blood clot in the leg, lung or another organ
you have systemic lupus erythematosus (SLE)
you have cancer. 4/10

For possible signs of a blood clot, see “Stop taking PAOSONELLE and contact your doctor immediately”.
Comparison
For women around the age of 50 not taking HRT, on average, 4–7 out of 1,000 are expected to develop a blood clot in a vein over a 5-year period.
For women around the age of 50 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 using combined estrogen-progestogen HRT have a slightly higher probability of developing heart disease compared to women not taking HRT.
Stroke
The risk of stroke is approximately 1.5 times higher in HRT users compared to non-users. The number of additional stroke cases due to HRT use increases with age.
Comparison
For women around the age of 50 not taking HRT, on average, 8 out of 1,000 have a chance of having a stroke over a 5-year period.
For women around the age of 50 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 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 PAOSONELLE may lower it. PAOSONELLE should not be used to treat high blood pressure.
If you are prone to developing discolored patches (melasma) on your face, avoid exposure to sunlight or ultraviolet light while taking PAOSONELLE.

Children and adolescents
Children and adolescents must not take PAOSONELLE.
Other medicines and PAOSONELLE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines can interfere with the effects of PAOSONELLE and cause irregular bleeding.
This includes the following medicines:

medicines for epilepsy (e.g. barbiturates, phenytoin, primidone, carbamazepine, oxcarbazepine, topiramate and felbamate)
medicines for tuberculosis (e.g. rifampicin and rifabutin)
medicines for HIV infection (e.g. nevirapine, efavirenz, ritonavir and nelfinavir)
herbal remedy containing St. John’s wort ( Hypericum perforatum )
medicines for treating fungal infections (such as griseofulvin, itraconazole, ketoconazole, voriconazole, fluconazole)
medicines for treating bacterial infections (such as clarithromycin, erythromycin)
medicines for treating certain heart conditions and high blood pressure (such as verapamil, diltiazem) 5/10
grapefruit juice.

HRT may interfere with the effectiveness of other medicines:

An antiepileptic medicine (lamotrigine), as this may increase the frequency of seizures.
Medicines for hepatitis C virus (HCV) (such as combination regimens with ombitasvir/paritaprevir/ritonavir with or without dasabuvir, and the regimen based on glecaprevir/pibrentasvir) may cause increases in blood test results related to liver function (elevated liver enzyme ALT) in women using COCs containing ethinylestradiol. PAOSONELLE contains estradiol instead of ethinylestradiol. It is not known whether an increase in liver enzyme ALT may occur when using PAOSONELLE with this HCV combination regimen.

The following medicines may cause small increases in serum potassium:

medicines used to treat:
inflammation or pain (e.g. acetylsalicylic acid (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 PAOSONELLE, a further reduction in blood pressure may occur.

Tell 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 PAOSONELLE, as this medicine may affect the results of certain tests.
Pregnancy and breastfeeding
PAOSONELLE is intended for use in postmenopausal women.
If you become pregnant, stop taking PAOSONELLE immediately and contact your doctor.
Driving and using machines
There is no reason to believe that the use of PAOSONELLE affects the ability to drive or operate machinery.
PAOSONELLE film-coated tablets contain lactose and soy lecithin
PAOSONELLE film-coated tablets contain 58.52 mg of lactose per film-coated tablet. If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.
PAOSONELLE film-coated tablets contain 0.070 mg of soy lecithin. If you are allergic to peanuts or soy, do not use this medicine.

3. How to take PAOSONELLE

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Your doctor will aim to prescribe the lowest effective dose needed to treat your symptoms for the shortest necessary duration. Speak to your doctor if you think the dose is too strong or not strong enough.
Your doctor will decide how long you should take PAOSONELLE.
Take one tablet daily, preferably at the same time each day. Swallow the tablet whole with some water. You may take PAOSONELLE with or without food.
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The strip contains 28 tablets. Next to each tablet is printed the day of the week on which it should be taken. For example, if you start on Wednesday, take the tablet next to which “WED” is printed. Follow the direction of the arrow on the packaging until you have taken all 28 tablets.
After taking all 28 tablets from the blister pack, continue treatment by starting a new pack without interruption.
Since each tablet contains the same amount of active substance, there will be no consequences if you make a mistake in the order of intake. However, it is recommended to maintain the correct sequence for better continuity of treatment.

If you are switching from another TOS preparation: Continue taking your current pack until it is finished and all tablets for that month have been taken. Take the first tablet of PAOSONELLE the day after. Do not leave a gap between your previous tablets and the PAOSONELLE film-coated tablets.

If this is your first TOS treatment: You may start taking PAOSONELLE film-coated tablets on any day.

If you take more PAOSONELLE than you should
If you have taken too many PAOSONELLE tablets by mistake, you may experience nausea, vomiting, or menstrual-like bleeding. Specific treatment is not required, but if you are concerned, consult your doctor or pharmacist.

If you forget to take PAOSONELLE
If you forget to take a tablet at your usual time and less than 24 hours have passed, take the missed tablet 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 remaining film-coated tablets at your usual time each day. Do not take a double dose to make up for the forgotten film-coated tablet.
If you forget to take the film-coated tablet for several days, irregular bleeding may occur.

If you stop taking PAOSONELLE
You may begin to experience again the typical symptoms of menopause, which may include hot flushes, sleep disturbances, nervousness, dizziness, or vaginal dryness. When you stop taking PAOSONELLE, you will also start to lose bone mass. If you wish to discontinue treatment with PAOSONELLE, consult your doctor or pharmacist. If you have any questions about the use of this medicine, consult your doctor or pharmacist.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following conditions have been reported more frequently in women using HRT compared to non-users:

breast cancer
excessive growth or cancer of the uterine lining (endometrial hyperplasia or cancer)
ovarian cancer 7/10
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 further information about these side effects, see section 2.
The following side effects have been associated with the use of PAOSONELLE:
Very common side effects (may affect more than 1 in 10 people):

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 PAOSONELLE. These episodes are usually temporary and typically resolve with continued treatment. If they do not, contact your doctor.
Common side effects (may affect up to 1 in 10 people):

depression, mood changes, nervousness
headache
stomach ache, nausea, stomach bloating
breast lumps (benign breast neoplasm), breast swelling
increased 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 (may affect up to 1 in 100 people):

weight gain or loss, loss or increase in appetite, increased blood fats
sleep disorders, anxiety, decreased sexual interest
burning or prickling sensation, reduced 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, vein inflammation, varicose veins
shortness of breath
stomach disorders, diarrhoea, constipation, vomiting, dry mouth, flatulence, taste alterations
altered liver enzymes (detectable in blood tests)
skin disorders, acne, hair loss, skin itching, excessive hair growth
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, vaginal thrush, vaginal dryness and itching, breast lumps (fibrocystic mastopathy), ovarian, cervical or uterine disorders, pelvic pain
generalized fluid retention, chest pain, general malaise, increased sweating.

Rare side effects (may affect up to 1 in 1,000 people):

anaemia
vertigo
ringing in the ears (tinnitus)
gallstones
muscle pain
inflammation of the Fallopian tubes 8/10
milk secretion from the nipples
chills

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

high potassium levels (hyperkalaemia), which sometimes causes 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 HRTs:

gallbladder diseases
various skin disorders:
skin discoloration, especially on the face or neck, known as “chloasma” or “melasma”
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, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at 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 PAOSONELLE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
This medicine 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 PAOSONELLE contains

The active substances are estradiol 1 mg (as 1.03 mg of estradiol hemihydrate) and drospirenone 2 mg in each film-coated tablet.

The other components are:
Coating film:
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Lecithin (soy).
Tablet core:
Lactose monohydrate
Corn starch
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Pregelatinized corn starch
Povidone K-25
Magnesium stearate.

Description of the appearance of PAOSONELLE and package contents
White or almost white, round, biconvex, film-coated tablet with a diameter of approximately 6 mm. On one side “GD3” is imprinted; the other side is not imprinted.
1×28, 3×28 film-coated tablets in transparent PVC/PVDC/Aluminum blisters, packed in cardboard boxes with a leaflet and a storage box, included in each box.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Gedeon Richter Plc.
Gyömrői út 19-21
1103 Budapest
Hungary

This medicinal product is authorized in the European Economic Area Member States under the following names:
Netherlands: Paosonelle 1 mg/2 mg filmomhulde tabletten
Belgium: Klimedix 1 mg/2 mg filmomhulde tabletten
Klimedix 1 mg/2 mg comprimé pelliculé
Klimedix 1 mg/2 mg Filmtabletten
Czech Republic: Paosonelle
Germany: Klimedix 1 mg/ 2 mg Filmtabletten
Spain: Paosonelle
Finland: Klimedix
France: PAOSONELLE 1 mg/2 mg comprimé pelliculé
Italy: PAOSONELLE
Latvia: Klimedix 1 mg/2 mg apvalkotās tabletes
Poland: Klimedix
Portugal: Klimedix
United Kingdom (Northern Ireland): Klimedix
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