Cliovelle 1 mg/0,5mg tabletki

Package Leaflet: Information for the User

Cliovelle 1 mg/0.5 mg tablets

Estradiol valerate + Norethisterone acetate

Read the package leaflet carefully before taking the medicine, as 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 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.

Table of Contents of the Leaflet

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

1. What is Cliovelle and what is it used for

Cliovelle is a Hormone Replacement Therapy (HRT).
It contains two types of female hormones, estrogen and progestogen.
Cliovelle is used in women who have reached the post-menopausal stage, at least 1 year after their last natural menstrual period.
Cliovelle is used to:

Relieve symptoms of the menopause

During the menopause, the amount of estrogen produced by the body decreases. This can cause symptoms such as hot flashes, night sweats, and vaginal dryness. Cliovelle alleviates these symptoms. Cliovelle should only be prescribed if your symptoms are severe enough to significantly affect your daily life.

Prevention of osteoporosis

After the menopause, some women may develop brittle bones (osteoporosis). All available options should be discussed with your doctor. If you are at increased risk of fractures due to osteoporosis and other medicines are not suitable, Cliovelle can be used to prevent osteoporosis after the menopause.

2. Important information before taking Cliovelle

Medical history and regular check-ups

Taking HRT is associated with risks, which need to be considered when deciding whether to start or continue treatment.
Experience with HRT in women with premature menopause (due to disease or removal of the ovaries) is limited. If you are being treated for premature menopause, the risks of HRT may be different. You should discuss this with your doctor.
Before you start (or restart) HRT, your doctor will ask about your medical history and that of your family. Your doctor may decide to perform a physical examination. This may include a breast examination and/or other internal examinations, if necessary.
If you start taking Cliovelle, you should have regular check-ups with your doctor (at least once a year). During these check-ups, you should discuss with your doctor the benefits and risks of continuing to take Cliovelle.
Regular breast examinations should be performed as recommended by your doctor.

When not to take Cliovelle

If any of the following conditions apply to you. If you are not sure, consult your doctorbefore taking Cliovelle.
Do not take Cliovelle:

• if you have or have had breast canceror are suspected of having it;
• if you have or have had estrogen-sensitive cancer, such as endometrial cancer (cancer of the lining of the uterus) or are suspected of having it;
• if you have unexplained vaginal bleeding;
• if you have untreated endometrial hyperplasia(thickening of the lining of the uterus);
• if you have or have had blood clots(thrombosis) in the legs or lungs (deep vein thrombosis or pulmonary embolism);
• if you have blood clotting disorders(such as protein C, protein S, or antithrombin deficiency);
• if you have or have had conditions caused by blood clots, such as a heart attack, stroke, or angina;
• if you have or have had liver diseaseor your liver test results have not returned to normal;
• if you have a rare blood disorder called porphyria(a genetic disorder);
• if you are allergicto estradiol valerate, norethisterone acetate, or any of the other ingredients of this medicine (listed in section 6).

If any of the above conditions occur for the first time while taking Cliovelle, stop taking Cliovelle and consult your doctor immediately.

Warnings and precautions

Before starting treatment, tell your doctor if you have ever had any of the following problems, as they may return or worsen during treatment with Cliovelle. If so, you may need to have more frequent check-ups. These problems include:

• uterine fibroids;
• endometriosis (a condition where tissue similar to the lining of the uterus grows outside the uterus) or a history of endometrial hyperplasia;
• an increased risk of blood clots (see "Blood clots in the veins (thrombosis)");
• an increased risk of estrogen-sensitive cancer (e.g., a family history of breast cancer);
• high blood pressure;
• liver disease, such as a benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• systemic lupus erythematosus (SLE, a disease that affects many organs);
• epilepsy;
• asthma;
• otosclerosis (a condition that affects the middle ear);
• high levels of triglycerides (a type of fat) in the blood;
• fluid retention due to heart or kidney problems
• hereditary or acquired angioedema.

Stop taking Cliovelle and consult your doctor immediately

if you notice any of the following:

• any of the conditions listed above as "Do not take Cliovelle";
• yellowing of the skin and whites of the eyes (jaundice), which may be a sign of liver disease;
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, with difficulty breathing, which may be a sign of angioedema;
• a significant increase in blood pressure (symptoms may include headaches, fatigue, dizziness);
• migraine headaches for the first time;
• becoming pregnant;
• symptoms of a blood clot, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• difficulty breathing.

Note:Cliovelle is not a contraceptive. If it has been less than 12 months since your last menstrual period or you are under 50 years old, you may need to use additional contraception to prevent pregnancy. Consult your doctor.

HRT and cancer

Endometrial hyperplasia (thickening of the lining of the uterus) and endometrial cancer

HRT that only contains estrogen increases the risk of endometrial hyperplasia and endometrial cancer.
The presence of progestogen in Cliovelle protects you from this additional risk.

Irregular bleeding

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

• lasts longer than 6 months,
• starts after 6 months of taking Cliovelle,
• continues after stopping Cliovelle, consult your doctor as soon as possible.

Breast cancer

Data confirm that taking HRT (estrogen alone or estrogen-progestogen combination) increases the risk of breast cancer. The additional risk depends on how long you take HRT. This additional risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time but may persist for 10 years or more if HRT lasted more than 5 years.
Comparison
In women aged 50-54 who do not take HRT, breast cancer is diagnosed in approximately 13-17 out of 1000 women over 5 years.
In women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1000 (i.e., 0-3 additional cases).
In women aged 50 who start 5-year estrogen-progestogen HRT, the number of cases will be 21 out of 1000 (i.e., 4-8 additional cases).
In women aged 50-59 who do not take HRT, breast cancer is diagnosed in approximately 27 out of 1000 women over 10 years.
In women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 out of 1000 (i.e., 7 additional cases).
In women aged 50 who start 10-year estrogen-progestogen HRT, the number of cases will be 48 out of 1000 (i.e., 21 additional cases).

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

• wrinkling of the skin,
• changes in the nipple,
• any lumps that can be felt or seen.

In addition, it is recommended to participate in breast cancer screening programs if they are available. When participating in breast cancer screening programs, it is essential to inform the nurse or medical staff performing the X-ray that you are taking HRT, as this may increase breast density, which can affect the mammography result.
If breast density is increased, the mammogram may not detect all tumors.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking HRT that only contains estrogen or a combination of estrogen and progestogen is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on age. For example, in women aged 50-54 who do not take HRT, ovarian cancer is diagnosed in approximately 2 out of 2000 women over 5 years.
In women who have taken HRT for 5 years, it will occur in approximately 3 out of 2000 women (i.e., 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in the veins (thrombosis)

The risk of blood clots in the veinsis 1.3 to 3 times higher in women taking HRT than in women not taking HRT, especially during the first year of treatment.
Blood clots can be life-threatening and if a clot reaches the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The risk of blood clots in the veins increases with age and if any of the following apply to you:

• you are unable to walk for a long time due to a major operation, injury, or illness (see section 3, "Surgery");
• you are severely overweight (BMI > 30 kg/m2);
• you have a blood clotting disorder that requires long-term treatment with a medicine used to prevent blood clots;
• a close relative has had a blood clot in the leg, lung, or other organ;
• you have systemic lupus erythematosus (SLE);
• you have cancer.

Symptoms of a blood clot, see "Stop taking Cliovelle and consult your doctor immediately".
Comparison
Observing women around the age of 50 who do not take HRT, approximately 4-7 out of 1000 will develop a blood clot in the veins over 5 years.
In women around the age of 50 who take estrogen-progestogen HRT for more than 5 years, approximately 9-12 out of 1000 will develop a blood clot in the veins (i.e., 5 additional cases).

Heart disease (heart attack)

There is no evidence that HRT prevents heart attacks.
Women over 60 years old taking estrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking HRT.

Stroke

The risk of stroke is about 1.5 times higher in women taking HRT than in those not taking HRT.
The number of additional stroke cases linked to HRT increases with age.
Comparison
Observing women around the age of 50 who do not take HRT, approximately 8 out of 1000 will have a stroke over 5 years.
In women around the age of 50 who take HRT, approximately 11 out of 1000 will have a stroke over 5 years (i.e., 3 additional cases).

Other conditions

HRT does not protect against memory loss. There is evidence of a higher risk of memory loss in women who start HRT after the age of 65. Consult your doctor.

Cliovelle and other medicines

Certain medicines may affect the way Cliovelle works. This may lead to irregular bleeding. These medicines include:

• medicines for epilepsy(such as phenobarbital, phenytoin, and carbamazepine);
• medicines for tuberculosis(such as rifampicin, rifabutin);
• medicines for HIV(such as nevirapine, efavirenz, telaprevir, ritonavir, and nelfinavir);
• herbal products containing St. John's Wort (Hypericum perforatum).

HRT may affect the way other medicines work:

• the anti-epileptic medicine lamotrigine, as it may increase the frequency of seizures.
• Treatment regimens for hepatitis C virus (HCV) infection using ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, using glecaprevir/pibrentasvir, or using sofosbuvir/velpatasvir/voxilaprevir may cause increased liver enzyme levels in the blood in women taking combined hormonal contraceptives containing ethinylestradiol. Cliovelle contains estradiol, not ethinylestradiol. It is not known whether increased liver enzyme levels may occur with Cliovelle. Your doctor will provide guidance.

Cliovelle may increase or decrease the effect of other medicines:

• the effect of cyclosporin (used to prevent transplant rejection, treat symptoms of rheumatoid arthritis, or treat psoriasis) may be increased.

Medicines containing ketoconazole (an antifungal medicine) may increase the effect of Cliovelle.
Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those that can be bought without a prescription, herbal medicines, or other natural products.
Your doctor will provide guidance.

Lab tests

If you are having a blood test, tell your doctor or the laboratory staff that you are taking Cliovelle, as this medicine may affect the results of some tests.

Pregnancy and breastfeeding

Cliovelle is for use in postmenopausal women only. If you become pregnant, stop taking Cliovelle and consult your doctor.

Driving and using machines

No effects on the ability to drive or use machines have been observed.

Cliovelle contains lactose

If you have been told that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Cliovelle

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Take one tablet every day, without interruption, from the blister pack.
Take the first tablet from the blister pack marked with the day of the week you start taking the tablets (e.g., "Mon" if you start on a Monday). Then take one tablet daily, following the direction of the arrows, until you have finished the pack. The next day, start a new pack.
Swallow the tablets with a large glass of water, preferably at the same time each day.
Your doctor will prescribe the lowest dose necessary to treat your symptoms and will advise you to take it for the shortest time necessary. If you think the dose is too strong or too weak, talk to your doctor.

What to do if you take more Cliovelle than you should

If you have taken more than the prescribed dose, contact your doctor or hospital for assessment and advice.
Overdose may cause breast tenderness, nausea, or vomiting, irregular menstrual bleeding, depression, fatigue, acne, or excessive hair growth on the body and face.
If you have taken an extra dose by mistake, take the next dose at the usual time the next day.

What to do if you forget to take Cliovelle

If you forget to take a tablet, take it within 12 hours of the usual time. If more than 12 hours have passed, skip the missed tablet and take the next tablet at the usual time the next day.
Do not take a double dose to make up for a missed dose.

What to do if you need to have surgery

If you are going to have surgery, tell the surgeon that you are taking Cliovelle. You may need to stop taking Cliovelle about 4 to 6 weeks before the operation to reduce the risk of blood clots (see section 2, "Blood clots in the veins (thrombosis)"). Ask your doctor when you can start taking Cliovelle again.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Cliovelle can cause side effects, although not everybody gets them.
Side effects are usually mild to moderate and do not require treatment to be stopped.
The following conditions are reported more frequently in women taking HRT compared to women not taking HRT:

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

The following side effects may occur while taking Cliovelle:

Very common (may affect more than 1 in 10 people)

Vaginal bleeding. Breast tenderness or pain.

Common (may affect up to 1 in 10 people)

Thrush (a fungal infection) in the genital area or vaginal thrush. Fluid retention. Depression or worsening of existing depression. Migraine or worsening of existing migraine, headaches. Nausea. Back pain. Uterine fibroids (non-cancerous growths in the uterus) or worsening of existing uterine fibroids. Peripheral edema (swelling of the hands and feet). Weight gain.

Uncommon (may affect up to 1 in 100 people)

Allergic reactions (hypersensitivity). Anxiety. Superficial thrombophlebitis (inflammation of the veins). Abdominal pain, discomfort, or tenderness. Gas, bloating. Hirsutism (excessive hair growth on the body and face), acne, hair loss. Itching. Hives. Leg cramps.

Rare (may affect up to 1 in 1000 people)

Blood clots in the lungs (see also section 2: "Important information before taking Cliovelle"). Deep vein thrombosis.

Very rare (may affect up to 1 in 10,000 people)

Anaphylactic reactions (severe, potentially life-threatening allergic reactions).
The following side effects have been reported with other HRTs:

• gallbladder disease
• various skin disorders:
• skin discoloration, especially on the face or neck, known as "pregnancy patches" (chloasma)
• painful red lumps on the skin (erythema nodosum)
• rash with target-shaped redness or blisters (erythema multiforme)
• dry eyes
• changes in the composition of the tear film.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309, website: https://smz.ezdrowie.gov.pl .
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cliovelle

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 blister pack and carton. The expiry date refers to the last day of that month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Cliovelle contains

• The active substances are estradiol 1 mg (as estradiol valerate) and norethisterone acetate 0.5 mg.
• The other ingredients are copovidone, lactose monohydrate, magnesium stearate, and maize starch.

What Cliovelle looks like and contents of the pack

White, round, biconvex tablets, 6 mm in diameter.
Calendar packs in blisters containing 28 and 84 tablets.
Blister packs containing 30 and 90 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

DR. KADE Pharmazeutische Fabrik GmbH
Rigistrasse 2
12277 Berlin
Germany
For further information, contact the representative of the marketing authorization holder:
Kadefarm Sp. z o.o.
ul. Gipsowa 18, Sierosław
62-080 Tarnowo Podgórne
Tel.: +48 61 862 99 43

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

Denmark
Cliovelle
Finland
Cliovelle 1 mg/0.5 mg tablets
Germany
Cliovelle 1 mg/0.5 mg tablets
Norway, Sweden
Cliovelle 1 mg/0.5 mg tablets
Poland
Cliovelle 1 mg/0.5 mg tablets

Date of last revision of the leaflet: 24-06-2025

Detailed information on this medicine is available on the website www.urpl.gov.pl.