CLIMEN 2 mg Tabletka Powlekana

Treść ulotki

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

Climen

2 mg coated tablets and 2 mg + 1 mg coated tablets
estradiol valerate (white tablets) and
estradiol valerate + cyproterone acetate (pink tablets)

Read this leaflet carefully before you start to use this medicine as 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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Climen and what is it used for

Climen is a cyclic estroprogestinic association of valerate estradiol and cyproterone acetate,
used for:

• hormone replacement therapy (HRT) of symptoms resulting from estrogen deficiency in post-menopausal women;
• prevention of osteoporosis in post-menopausal women at high risk of future fractures, who present intolerances or specific contraindications to other medicinal products authorized for the prevention of osteoporosis. Experience in the treatment of women over 65 years of age is limited.

2. What you need to know before taking Climen

Medical examination and regular check-ups
The use of HRT involves risks that must be considered when deciding whether to start or
continue therapy.
Experience in treating women with early menopause (due to cessation of ovulation or
surgery) is limited. If you have early menopause, the risks associated with the use of HRT may
be different. Consult your doctor.
Before starting (or restarting) HRT, your doctor will ask you some questions about your health
history and that of your family. Your doctor may decide to perform some tests. These may
include a breast exam and/or a pelvic exam if necessary.
Once you have started treatment with Climen, you will need to see your doctor for regular check-ups (at least once
a year). During these check-ups, discuss with your doctor the benefits and risks associated with
continuing treatment with Climen.
Have regular breast exams, as recommended by your doctor.

Do not take Climen
if any of the conditions listed below apply to you. If you are unsure about the conditions described
below, consult your doctorbefore taking Climen.
Do not take Climen:

• if you are allergicto valerate estradiol,ciproterone acetateor any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant or breastfeeding;
• if you have, have had or suspect you have malignant breast tumor;
• if you have had or suspect you have a malignant tumor whose growth is sensitive to estrogens, such as a tumor of the uterine lining (endometrium);
• if you have or have been treated in the past for the presence of blood clots inside a vein(thrombosis) such as those in the legs (deep vein thrombosis) or those in the lungs (pulmonary embolism);
• if you have blood clotting problems(such as deficiencies of protein C, protein S or antithrombin);
• if you have or have recently had a disease caused by blood clots in the arteries such as heart attack, strokeor angina(chest pain);
• if you have or have had in the past a liver diseaseand your liver function values have not returned to normal;
• if you have unexplained vaginal bleeding;
• if you suffer from a thickening of the uterine lining(endometrial hyperplasia) that has not been treated;
• if you have a rare blood disease that is inherited (familial) called “porphyria”;
• if you have a meningioma or have been diagnosed with a meningioma in the past (a generally benign tumor of the tissue layer located between the brain and the skull).

If any of these conditions occur for the first time during the use of Climen, stop
treatment immediately and consult your doctor.

Warnings and precautions
Talk to your doctor or pharmacist before taking Climen.
When to be particularly careful with Climen
Tell your doctor if you have had any of the following conditions in the past, before starting
treatment, as these may recur or worsen during treatment with Climen. If this happens,
you should see your doctor more often for check-ups:

• uterine fibroids;
• growth of uterine lining in other locations (endometriosis) or a history of excessive growth of the uterine lining (endometrial hyperplasia);
• increased risk of developing blood clots (see below “Effects of HRT on the heart and circulation - “Blood clots in a vein (thrombosis)”)
• increased risk of tumors sensitive to estrogens (e.g. if you have a mother, sister or grandmother who has had breast cancer);
• high blood pressure;
• liver disease such as a benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• a disease of the immune system that affects many organs of the body (Systemic Lupus Erythematosus or SLE);
• epilepsy;
• asthma;
• a disease affecting the eardrum and hearing (otosclerosis);
• very high levels of fat in the blood (triglycerides);
• fluid retention due to heart or kidney problems;
• benign breast disease;
• chorea minor (rapid, uncoordinated and involuntary movements);
• if you suffer from an adenoma (benign tumor) of the pituitary gland, you will need to be carefully monitored by your doctor, who will prescribe periodic measurements of prolactin levels;
• hereditary and acquired angioedema

Stop taking Climen and contact your doctor immediately if:

• any condition described in the “Do not take Climen” section;
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of a liver disease;
• marked increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• migraine-type headache that occurs for the first time;
• you become pregnant;
• you notice signs of a blood clot, such as:
• painful swelling and redness of the legs
• sudden chest pain
• difficulty breathing
• swelling of the face, tongue and/or throat and/or difficulty swallowing or hives with difficulty breathing which are indicative of angioedema.

For more information see below the section “Effects of HRT on the heart and circulation” -
Blood clots in veins (thrombosis)”.

Note: Climen 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 HRT based on estrogen alone increases the risk of excessive thickening of the
uterine lining (endometrial hyperplasia) and that of cancer of the uterine lining (endometrial
carcinoma).
The presence of a progestin in Climen, protects you from this additional risk.
In women who still have a uterus and who are not taking HRT, on average, 5 out of 1000 will be diagnosed with
endometrial carcinoma between the ages of 50 and 65. For women between the ages of 50 and 65 who
still have a uterus and are taking HRT with estrogen alone, between 10 and 60 out of 1000 women will be
diagnosed with endometrial carcinoma (i.e. between 5 and 55 additional cases), depending on the dose and duration
of use.

Irregular bleeding
You will have bleeding once a month (called breakthrough bleeding) while taking Climen.
But, if you have unexpected bleeding or spotting outside of your monthly bleeding,
which:

• continues for more than the first 6 months
• occurs after you have been taking Climen for more than 6 months
• continues after stopping Climen see your doctor as soon as possible.

Breast cancer
If you have or have had breast cancer, you should not take this medicine(see “Do not take
Climen”). Evidence shows that taking hormone replacement therapy (HRT) based on
estrogens and progestins combined or based on estrogen alone increases the risk of breast cancer. The
additional risk depends on the duration of HRT use. This additional risk manifests within 3
years of use. After stopping HRT, the additional risk will decrease over time, but this risk
may persist for 10 years or more if HRT is used for more than 5 years.
If you have a close relative (mother, sister or grandmother) who has had breast cancer, your doctor may
subject you to more frequent check-ups.
Comparison
In women between the ages of 50 and 54 who are not following HRT, breast cancer will be
diagnosed in an average of about 13-17 women out of 1000 over a period of 5 years. In women aged 50 who
begin to follow HRT based on estrogen alone for a period of 5 years, 16-17 cases will occur
out of 1000 users (i.e. 0-3 additional cases). In women aged 50 who begin to follow HRT based on
estrogens and progestins combined for 5 years, there will be 21 cases out of 1000 women treated (i.e. 4 to 8 cases
more).

In women between the ages of 50 and 59 who are not following HRT, breast cancer will be
diagnosed in an average of 27 women out of 1000 over a period of 10 years.
In women aged 50 who begin to follow HRT based on estrogen alone for 10 years, 34 cases will occur
out of 1000 users (i.e. 7 additional cases).
In women aged 50 who begin to follow HRT based on estrogens and progestins combined for 10
years, 48 cases will occur out of 1000 users (i.e. 21 additional cases).

Check your breasts regularly. See your doctor if you notice any changes such as:

• small depressions on the skin;
• changes in the nipple;
• any visible or palpable hardening.

In addition, it is recommended to participate in mammography screening programs when they are offered to you. For
mammography screening, it is important that you inform the nurse/healthcare worker performing the
radiograph that you are using HRT, as this treatment may increase breast density which could
alter the mammography result. Where breast density is increased, mammography may not detect all nodules.

Ovarian cancer
Ovarian cancer is rare - much rarer than breast cancer.
The use of estrogen-only or estrogen-progestin-based therapy has been associated with a slight increase in the
risk of ovarian cancer. The risk of ovarian cancer varies depending on age. For example, in women between the ages of
50 and 54 who are not taking HRT, about 2 out of 2,000 will be diagnosed with
ovarian cancer over a 5-year period. For women who are taking HRT for 5 years, there will be about
3 cases out of 2,000 women treated (i.e., about 1 additional case).

Liver tumors
After the use of hormonal substances such as those contained in Climen, benign and, more rarely, malignant liver tumors have been observed in rare cases. In isolated cases, these tumors have caused
intra-abdominal bleeding which may be life-threatening. Although these events are extremely
unlikely, you should tell your doctor if you experience any unusual abdominal pain that does not go away in
a short time.
Effects of HRT on the heart and circulation

Blood clots in a vein (thrombosis)
HRT may increase the risk of blood clots in the veinsin users by 1.3 to 3 times compared to
non-users, 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 having a blood clot in the veins increases with age and if any of the following conditions apply to you. Tell your doctor if any of the following conditions apply to you:
o you are unable to walk for a long period due to major surgery,
accident or illness (see also section 3, “If you are going to have surgery”)
o you are severely overweight (BMI> 30 kg/m)
o you have any blood clotting problems that require long-term treatment
with a medicine that prevents blood clots
o if a close relative of yours has had a blood clot in the leg, lung or another organ
o you have Systemic Lupus Erythematosus (SLE)
o you have cancer.
For possible signs of a blood clot, see “Stop using Climen and contact your doctor immediately”
Comparison
For women around the age of 50 who are not taking HRT, on average, in a 5-year period,
4-7 cases out of 1000 are expected to have a blood clot in a vein.
For women around the age of 50 who are taking estro/progestin HRT for more than 5 years, there will be 9-12 cases out of 1000 users (i.e. an increase of 5 cases).

Heart disease (heart attack)
There is no evidence that HRT can prevent a heart attack.
Women over the age of 60 who use estro/progestin HRT have a slightly higher probability of developing heart disease compared to women who do not take any
HRT.

Stroke
The risk of having a stroke is about 1.5 times higher in HRT users compared to non-users. The number of additional cases of stroke due to HRT use will increase with age.
Comparison
For women around the age of 50 who are not taking HRT, on average, in a 5-year period, 8 cases out of 1000 have the possibility of having a stroke. For women around the age of 50 who are
taking estro/progestin HRT for over 5 years, there will be 11 cases out of 1000 users (i.e. an
increase of 3 cases).

Meningioma
For high doses (equal to or greater than 25 mg) of ciproterone acetate, an increased risk of a benign brain tumor (meningioma) has been reported. If you have been diagnosed with a meningioma, your doctor will discontinue the administration of all medicines containing ciproterone, including Climen, as a precautionary measure (see paragraph ‘Do not take Climen’).

Other conditions

• HRT does not prevent memory loss. The risk of memory loss may be greater in women who start using HRT after the age of 65. Ask your doctor for advice.
• If you have a tendency to develop patchy brown spots (chloasma) on your face, you should minimize exposure to the sun or ultraviolet rays during treatment with Climen.
• Your doctor will monitor you carefully if you have heart or kidney problems, as taking estrogens can lead to fluid retention.
• During estrogen therapy, some women are particularly predisposed to the formation of gallstones.
• You may experience abnormal uterine bleeding.
• Estrogens can increase the levels of certain plasma proteins (TGB, corticosteroid-binding globulin, SHBG, angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

Other medicines and Climen
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those available without a prescription, herbal medicines, or other natural products.
Some medicines can interfere with the effects of Climen. This can cause irregular bleeding.
This applies to the following medicines:

• medicines for epilepsy(e.g. barbiturates, phenytoin, primidone, carbamazepine and probably oxcarbazepine, topiramate and felbamate);
• Medicines for tuberculosis(e.g. rifampicin, rifabutin);
• Medicines for HIVand hepatitis C virusinfections, called protease inhibitors and non-nucleoside reverse transcriptase inhibitors (such as nevirapine, efavirenz, ritonavir and nelfinavir);
• Herbal preparations containing St John's Wort(Hypericum perforatum);
• Medicines for the treatment of fungal infections(such as griseofulvin, fluconazole, itraconazole, ketoconazole and voriconazole);
• Medicines for the treatment of bacterial infections(such as clarithromycin, erythromycin, penicillins and tetracyclines);
• Medicines for the treatment of certain heart diseases, high blood pressure(such as verapamil and diltiazem);
• Grapefruit juice;
• Medicines against the hepatitis C virus (HCV) (such as a combination regimen with ombitasvir/paritaprevir/ritonavir with or without dasabuvir, as well as a regimen based on glecaprevir/pibrentasvir) can cause increases in blood test results concerning liver function (increased liver enzyme ALT) in women using COCs containing ethinylestradiol. Climen contains estradiol instead of ethinylestradiol. It is not known whether an increase in liver enzyme ALT can occur when using Climen with this combination regimen against HCV. Your doctor will give you the necessary instructions.

Paracetamol may cause an increase in the amount of estradiol absorbed into the blood.
If you have diabetes, your doctor may adjust your treatment regimen.

Laboratory tests
If you need blood tests, tell your doctor or laboratory personnel that you are taking Climen, because this medicine can affect the results of some tests.

Pregnancy and breastfeeding
Climen is to be used only in postmenopausal women. If you are or suspect you are pregnant, do not take this medicine (see “Do not take Climen”). If you become pregnant, stop taking Climen and contact your doctor.
Climen is contraindicated during breastfeeding.

Driving and using machines
No effects on the ability to drive or operate machinery have been observed in users of Climen.

Climen contains lactose and sucrose
If your doctor has diagnosed you with intolerance to certain sugars, contact him or her before taking this medicine.

3. How to take Climen

Take this medicine always exactly as your doctor has instructed. If you have any doubts, ask your doctor or pharmacist.
Women with amenorrhea (of proven non-pregnancy origin) and those in post-menopause can start treatment at any time.
Take one white tablet daily for the first 11 days and one pink tablet for the next 10 days.
Treatment should be started by taking the first tablet from the white series, the compartment of which is
marked with the word "START". Subsequent daily tablets should be taken from the following compartments in the
direction of the arrows printed on the package.
This way, all the white tablets will be taken first, then all the pink ones.
To facilitate adherence to the treatment schedule, the package is equipped with a sticker showing the days of
the week. This label should be applied in the designated space on the package, ensuring that the day of the
week on which treatment is started corresponds to the sector where the word "START" is indicated. This will
make it easier to verify the correct daily intake of the tablets.
Swallow the tablets whole, without chewing, with some liquid, preferably at the same time each day (e.g. after
breakfast or after dinner).
At the end of the package (21 days of treatment) there will be a 7-day break during which, in women with a still
present uterus, bleeding similar to menstruation will occur. If bleeding does not occur during the 7-day break,
the use of Climen in the next cycle can only occur after excluding pregnancy (see “Pregnancy and breastfeeding”).
The new package must be started, after the 7-day break, on the same day of the week as the previous package.
The doctor will prescribe the lowest dose to treat your symptoms and for the shortest necessary period.
Consult your doctor if you think the dose is too high or not high enough.

Additional information for particular categories of patients
Use in children and adolescents
Climen is not indicated for use in children and adolescents.

Use in the elderly
There are no data to indicate the need for dosage adjustment in elderly patients. Tell your doctor if you are
over 65 years old (see “Warnings and precautions”).

Use in patients with impaired liver function
Formal studies have not been conducted in patients with impaired liver function. Climen is contraindicated in
women with severe liver disease (see “Do not take Climen”).

Use in patients with impaired kidney function
Formal studies have not been conducted in patients with impaired kidney function.

If you need surgery
If you are going to have surgery, tell the surgeon that you are using Climen. It may be necessary to stop taking
it about 4-6 weeks before the operation to reduce the risk of a blood clot (see “Blood clots in a vein”). Ask your
doctor when you can start using Climen again.

If you take more Climen than you should
Overdosage can cause nausea and vomiting and irregular bleeding. No specific treatment is necessary but consult
your doctor if you are concerned.

If you forget to take Climen
If you forget to take a tablet, you should take it as soon as possible. Take the next tablet at the usual time.
If more than 24 hours have passed, the forgotten tablet should be discarded.

Do not take a double dose to make up for the forgotten tablet.
Forgetting one or more Climen tablets may increase the likelihood of breakthrough bleeding and spotting (uterine
bleeding).
If you have any questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following diseases are reported more frequently in women using TOS compared to non-users:

• breast cancer;
• excessive growth or cancer of the uterine lining (hyperplasia or endometrial cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• probable memory loss if TOS is started after the age of 65.

For more information about these side effects, see paragraph 2.
The following side effects have been observed with Climen. These generally disappear
after the first few months of treatment and can be divided as follows:

Common side effects(may affect up to 1 in 10 users):

• weight gain/loss;
• headache;
• abdominal pain, nausea;
• skin rash, itching;
• uterine/vaginal bleeding, including spotting (light bleeding between periods).

Uncommon side effects(may affect up to 1 in 100 users):

• hypersensitivity reaction;
• depressed mood;
• dizziness;
• visual disturbances;
• palpitations;
• dyspepsia (indigestion);
• erythema nodosum (a disease characterized by red nodules under the skin, located on the legs and feet, more rarely on the forearms), urticaria (a skin rash similar to nettle stings, accompanied by a burning and itching sensation);
• breast pain, breast tenderness;
• edema.

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

• anxiety, increased/decreased libido;
• migraine;
• contact lens intolerance;
• flatulence (gas in the intestines), vomiting;
• hirsutism (excessive hair growth), acne;
• muscle cramps;
• dysmenorrhea (painful periods), vaginal discharge, symptoms that mimic premenstrual syndrome, breast enlargement;
• fatigue.

In women with hereditary angioedema, exogenous estrogens may induce or worsen the symptoms
of angioedema (see “Warnings and precautions”).

The following side effects have been reported with other TOS:

• gallbladder diseases
• a number of skin diseases:
• alteration of skin color, especially on the face or neck, known as “chloasma” (pregnancy mask)
• reddish and painful skin nodules (erythema nodosum)
• skin rash with redness or target-shaped lesions (erythema multiforme)
• vascular purpura (pinpoint hemorrhages of the skin and mucous membranes)

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through 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 Climen

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 after “Exp.”. The expiry date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Climen contains

• The active ingredient is estradiol valerate. Each white coated tabletcontains 2.0 mg of estradiol valerate;
• The other ingredients are: lactose, corn starch, povidone 25.000, talc, magnesium stearate, sucrose, povidone 700.000, macrogol 6.000, calcium carbonate, wax E.
• The active ingredients are estradiol valerate and cyproterone acetate. Each pink coated tabletcontains 2.0 mg of estradiol valerate and 1.0 mg of cyproterone acetate.
• The other ingredients are: lactose, corn starch, povidone 25.000, talc, magnesium stearate, sucrose, povidone 700.000, macrogol 6.000, calcium carbonate, wax E, glycerol 85%, titanium dioxide, yellow iron oxide, red iron oxide.

Description of the appearance of Climen and contents of the pack
Climen is available as coated tablets.
The calendar pack contains 21 coated tablets (11 white tablets and 10 pink tablets).

Marketing Authorisation Holder
Bayer S.p.A. Viale Certosa 130, 20156 Milano.

Manufacturer
Delpharm Lille SAS, Parc d'Activités Roubaix-Est, 22 Rue de Toufflers, CS 50070, 59452 Lys-Lez-Lannoy,
France