Klimedix

Leaflet attached to the packaging: patient information

Klimedix, 1 mg + 2 mg, coated tablets

Estradiol + Drospirenone

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What is Klimedix and what is it used for

Klimedix is a medicine used in Hormone Replacement Therapy (HRT). It contains two types of female hormones: estrogen and progestogen. Klimedix is used in postmenopausal women, at least 12 months (1 year) after their last natural menstrual period.

Klimedix is used for:

Relieving symptoms that occur after menopause

During menopause, the amount of estrogen produced by the woman's body decreases. This can cause symptoms such as a feeling of heat on the face, neck, and chest ("hot flashes"). Klimedix relieves these symptoms that occur after menopause. Klimedix will only be prescribed if the symptoms significantly disrupt the patient's daily life.

Preventing osteoporosis

After menopause, some women may develop brittle bones (osteoporosis). You should discuss all available treatment options with your doctor. In women at high risk of future fractures due to osteoporosis, for whom other treatments cannot be used, Klimedix may be used to prevent osteoporosis after menopause.

2. Important information before taking Klimedix

Medical history and regular medical examinations

Taking HRT involves risks that need to be considered when deciding to start or continue treatment. Experience with treating women with premature menopause (due to ovarian failure or surgery) is limited. In women with premature menopause, the risks associated with HRT may be different. In such cases, you should consult a doctor. Before starting (or re-starting) HRT, the doctor will take a medical history of the patient and her family. The doctor may decide that a medical examination is necessary. The doctor may examine the breasts and (if necessary) perform an internal examination. After starting Klimedix, the patient should have regular medical examinations (at least once a year). During these visits, the patient should discuss the benefits and risks of continuing to take Klimedix with her doctor.

You should regularly examine your breasts, as recommended by your doctor.

Do not take Klimedix:

If any of the following conditions apply to you. If you are unsure whether any of the following conditions apply to you, you should consult your doctor before taking Klimedix.

Do not take Klimedix:

• if you have or have had breast cancer or if breast cancer is suspected;
• if you have a tumor that is sensitive to estrogens, such as endometrial cancer (cancer of the lining of the uterus) or if it is suspected;
• if you have unexplained vaginal bleeding;
• if you have untreated endometrial hyperplasia (excessive thickening of the lining of the uterus);
• if you have or have had a blood clot in a vein (deep vein thrombosis), for example in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• if you have a known tendency to form blood clots (such as protein C, protein S, or antithrombin deficiency);
• if you have or have had a blood clot-related disease in an artery, such as a heart attack, stroke, or angina pectoris;
• if you have or have had liver disease and liver function tests have not returned to normal;
• if you have a rare, inherited blood disorder called porphyria;
• if you have severe kidney disease or acute kidney failure;
• if you are allergic (hypersensitive) to estrogens, progestogens, or any of the other ingredients of Klimedix (listed in section 6);
• if you are allergic to peanuts or soy.

If you experience any of the above symptoms while taking Klimedix, you should stop taking the medicine and consult your doctor immediately.

Warnings and precautions

You should discuss this with your doctor or pharmacist before starting Klimedix. If you have ever had any of the following problems, you should tell your doctor before starting treatment, as these conditions may recur or worsen during treatment with Klimedix. In these cases, you should have more frequent check-ups with your doctor:

• uterine fibroids;
• endometriosis (growth of uterine tissue outside the uterus) or endometrial hyperplasia (excessive thickening of the uterine lining) in the past;
• increased risk of blood clots (see "Blood clots in a vein (thrombosis)");
• increased risk of estrogen-sensitive tumors (e.g., breast cancer in the mother, sister, or grandmother);
• high blood pressure;
• liver disease, such as a benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• an immune system disease that can affect many organs (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• ear and hearing problems (otosclerosis);
• very high levels of fats in the blood (triglycerides);
• fluid retention due to heart or kidney failure.

You should stop taking Klimedix and consult your doctor immediately

If you experience any of the following symptoms while taking HRT:

• any of the conditions listed in the "Do not take Klimedix" section;
• yellowing of the skin or whites of the eyes (jaundice), which can be a sign of liver disease;
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• the onset of migraine-like headaches for the first time;
• becoming pregnant;
• symptoms that may indicate a blood clot, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• difficulty breathing (shortness of breath).

Note: Klimedix is not a contraceptive. Women who have not had a menstrual period for 12 months or are under 50 years old may still need to use additional contraception to prevent pregnancy. You should consult your doctor for advice.

HRT and cancer

Endometrial hyperplasia (excessive thickening of the uterine lining) and endometrial cancer

Taking only estrogens in HRT increases the risk of endometrial hyperplasia and endometrial cancer. The progestogen in Klimedix protects against this additional risk.

Irregular bleeding

During the first 3-6 months of taking Klimedix, irregular bleeding or spotting may occur. However, if irregular bleeding:

• persists after the first 6 months of treatment,
• occurs after a period of more than 6 months after starting Klimedix,
• continues after stopping Klimedix you should consult your doctor as soon as possible.

Breast cancer

Evidence suggests that taking combined estrogen-progestogen or estrogen-only HRT is associated with an increased 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. = ComparisonIn women aged 50-54 who do not take HRT, breast cancer is diagnosed in approximately 13-17 per 1,000 women over a 5-year period. In women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 per 1,000 patients (i.e., 0-3 additional cases). In women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 per 1,000 patients (i.e., 4-8 additional cases). In women aged 50-59 who do not take HRT, breast cancer is diagnosed in approximately 27 per 1,000 women over a 10-year period. In women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 per 1,000 patients (i.e., 7 additional cases). In women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 per 1,000 patients (i.e., 21 additional cases).

The patient should regularly examine their breasts. If any of the following changes occur, they should consult their doctor:

• retraction or dimpling of the skin;
• changes in the nipple;
• any noticeable or palpable lumps.

In addition, it is recommended to participate in screening mammography if it is offered. In the case of screening mammography, it is essential to inform the nurse/medical staff performing the X-ray that you are taking HRT, as this medicine may increase breast density, which can affect the mammography result. In the case of increased breast density, mammography may not detect all lumps.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking HRT that contains only estrogens or a combination of estrogens and progestogens 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 will be diagnosed in approximately 2 per 2,000 women over a 5-year period. In women who have taken HRT for 5 years, it will occur in approximately 3 per 2,000 women (i.e., approximately 1 additional case).

Effect of HRT on the heart and blood vessels

Blood clots in a vein (thrombosis)

The risk of blood clots in the veins is approximately 1.3 to 3 times higher in women taking HRT, especially in the first year of treatment, than in those not taking HRT. Blood clots can be life-threatening, especially if one of them travels to the lungs, causing chest pain, shortness of breath, fainting, or even death. The risk of blood clots increases with age and if any of the following conditions apply to you. You should inform your doctor:

• if you are unable to walk for a long time due to a major operation, injury, or illness (see also section 3 "If you are going to have surgery");
• if you are severely overweight (BMI >30 kg/m2);
• if you have blood clotting problems that require long-term administration of medicines to prevent blood clots;
• if your close relatives have had blood clots in the legs, lungs, or other organs;
• if you have systemic lupus erythematosus (SLE);
• if you have cancer.

Symptoms that may indicate a blood clot are listed in the "Stop taking Klimedix and consult your doctor immediately" section. ComparisonIn women around the age of 50 who do not take HRT, it can be expected that approximately 4-7 per 1,000 women will develop a blood clot in the veins over a 5-year period. In women around the age of 50 who take combined estrogen-progestogen HRT for more than 5 years, approximately 9-12 such cases will occur per 1,000 patients (i.e., 5 additional cases).

Heart disease (heart attack)

It has not been proven that HRT prevents heart attacks. In women over 60 who take combined estrogen-progestogen HRT, the risk of heart disease is slightly higher than in women not taking HRT.

Stroke

The risk of stroke in women taking HRT is approximately 1.5 times higher than in women not taking HRT. The number of additional stroke cases associated with HRT increases with age. ComparisonIn women around the age of 50 who do not take HRT, it is expected that approximately 8 per 1,000 women will have a stroke over a 5-year period. In women around the age of 50 who take HRT, this value is 11 cases per 1,000 patients over a 5-year period (i.e., 3 additional cases).

Other diseases

• HRT does not prevent memory loss. There is some evidence that women who start taking HRT after the age of 65 may experience greater memory loss. You should discuss this with your doctor.
• If you have kidney problems and high potassium levels in the blood, especially if you are taking medicines that increase potassium levels, your doctor may check your potassium levels in the first month of treatment.
• If you have high blood pressure, taking Klimedix may lower it. You should not take Klimedix to treat high blood pressure.
• If you have a tendency to develop patchy skin discoloration (chloasma) on your face, you should avoid exposure to the sun or ultraviolet radiation while taking Klimedix.

Children and adolescents

Children and adolescents should not take Klimedix.

Klimedix and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. Some medicines (listed below) may affect the action of Klimedix, which can lead to irregular bleeding. This applies to the following medicines:

• medicines used to treat epilepsy (such as barbiturates, phenytoin, primidone, carbamazepine, oxcarbazepine, topiramate, and felbamate);
• medicines used to treat tuberculosis (such as rifampicin, rifabutin);
• medicines used to treat HIV and hepatitis C virus infections (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors, e.g., nevirapine, efavirenz, nelfinavir, and ritonavir);
• St. John's Wort (Hypericum perforatum);
• medicines used to treat fungal infections (such as griseofulvin, itraconazole, ketokonazole, voriconazole, fluconazole);
• medicines used to treat bacterial infections (such as clarithromycin, erythromycin);
• medicines used to treat certain heart diseases, high blood pressure (such as verapamil, diltiazem);
• grapefruit juice.

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

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

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those that are available without a prescription, herbal medicines, and other natural products.

Lab tests

If a blood test is necessary, you should inform your doctor or medical staff that you are taking Klimedix, as this medicine may affect the results of some tests.

Pregnancy and breastfeeding

Klimedix is intended for postmenopausal women. If you become pregnant, you should stop taking Klimedix and consult your doctor.

Driving and using machines

There is no evidence that Klimedix affects the ability to drive or use machines.

Klimedix contains lactose and soy lecithin

Klimedix contains 58.52 mg of lactose per coated tablet. If you have been diagnosed with intolerance to some sugars, you should consult your doctor before taking this medicine. Klimedix contains 0.070 mg of soy lecithin per coated tablet. If you are allergic to peanuts or soy, you should not take this medicine.

3. How to take Klimedix

This medicine should always be taken exactly as prescribed by your doctor. If you are unsure, you should consult your doctor or pharmacist. Your doctor will aim to prescribe the lowest dose to treat your symptoms for as short a period as necessary. If you think the dose is too strong or too weak, you should consult your doctor. Your doctor will decide how long you should take Klimedix. You should take one tablet a day, preferably at the same time. Swallow the tablet whole with water. Klimedix can be taken with or without food. The packaging contains 28 tablets. On the packaging (blister pack), the day of the week is printed next to each tablet, on which you should take that tablet. If, for example, you start on a Wednesday, take the tablet with "Wed" printed next to it. Follow the direction of the arrows on the packaging until you have taken all 28 tablets. After taking all 28 tablets from the blister pack, you should continue treatment by starting a new pack without interruption. Each tablet contains the same amount of active substances, so if you make a mistake in the order of taking them, it will not have any consequences. However, it is recommended to maintain the correct order to ensure better continuity of treatment. If you are taking another HRT:you should continue taking your current medicine until you finish the pack and take all the tablets for that month. You should take the first tablet of Klimedix the next day. Do not take a break between your current medicine and Klimedix. If you are taking HRT for the first time:you can start taking Klimedix tablets on any day.

Taking more than the recommended dose of Klimedix

If you accidentally take too many Klimedix tablets, you may experience nausea, vomiting, and bleeding similar to a menstrual period. There is no need for special treatment, but if you are unsure, you should consult your doctor or pharmacist.

Missing a dose of Klimedix

If you forget to take a tablet at the usual time and the delay is less than 24 hours, you should take it as soon as possible. Take the next tablet at the usual time. If the delay is more than 24 hours, you should leave the missed tablet in the packaging. Continue taking the remaining tablets at the usual time every day. Do not take a double dose to make up for the missed dose of Klimedix. If you forget to take tablets for several days, you may experience irregular bleeding.

Stopping Klimedix treatment

You may experience typical menopausal symptoms, including hot flashes, sleep disturbances, nervousness, dizziness, or vaginal dryness. You may start to lose bone mass after stopping Klimedix. If you want to stop taking Klimedix, you should discuss this with your doctor or pharmacist. If you have any further doubts about taking this medicine, you should consult your doctor or pharmacist.

If you are going to have surgery

If you are scheduled for surgery, you should inform your surgeon that you are taking Klimedix. It may be necessary to stop taking Klimedix about 4-6 weeks before the planned surgery to reduce the risk of blood clots (see section 2 "Blood clots in a vein"). You should ask your doctor when you can resume taking Klimedix.

4. Possible side effects

Like all medicines, Klimedix can cause side effects, although not everybody gets them. The following diseases are reported more frequently in women taking HRT than in women not taking HRT:

• breast cancer,
• abnormal growth or cancer of the uterine lining (endometrial hyperplasia or endometrial 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.

Detailed information on these side effects can be found in section 2. The following side effects have been associated with Klimedix:

Very common side effects(occurring in at least 1 in 10 patients):

• unexpected bleeding similar to a menstrual period (see also section 2 "HRT and cancer"),
• breast tenderness,
• breast pain.

Unexpected bleeding similar to a menstrual period usually occurs in the first few months of taking Klimedix. It is usually temporary and disappears during continued treatment. If it does not, you should consult your doctor. Common side effects(occurring in 1 in 10 patients):

• depression, mood changes, nervousness,
• headache,
• abdominal pain, nausea, bloating,
• breast lumps (benign breast tumors), breast swelling,
• enlargement of uterine fibroids,
• non-cancerous growth of cells on the cervix,
• irregular vaginal bleeding,
• discharge,
• weakness, localized fluid retention.

Uncommon side effects(occurring in 1 in 100 patients):

• weight gain or loss, decreased or increased appetite, increased levels of fats in the blood,
• sleep disturbances, anxiety, decreased sex drive,
• tingling or prickling sensation, decreased concentration, dizziness,
• eye problems (e.g., red eyes), vision disturbances (e.g., blurred vision),
• palpitations,
• blood clots, deep vein thrombosis (see also section 2 "Blood clots in a vein"), high blood pressure, migraine, inflammation of the veins, varicose veins,
• shortness of breath,
• gastrointestinal disturbances, diarrhea, constipation, vomiting, dry mouth, bloating, taste disturbances,
• changes in liver enzyme activity (visible in blood tests),
• skin problems, acne, excessive hair loss (alopecia), itching, excessive hair growth,
• back pain, joint pain, limb pain, muscle cramps,
• urinary tract disorders and infections,
• breast cancer, endometrial hyperplasia, benign uterine tumor, thrush, vaginal dryness and itching, breast lumps (fibrocystic breast changes), ovarian disorders, cervical disorders and uterine disorders, pelvic pain,
• generalized fluid retention, chest pain, malaise, increased sweating.

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

• anemia,
• dizziness,
• ringing in the ears,
• gallstones,
• muscle pain,
• inflammation of the fallopian tubes,
• milk discharge from the nipples,
• chills.

In clinical trials, the following side effects were reported in women with high blood pressure:

• increased potassium levels in the blood (hyperkalemia), which can sometimes lead to muscle cramps, diarrhea, nausea, and dizziness or headache
• heart failure, heart enlargement, palpitations, arrhythmias
• increased aldosterone levels in the blood.

The following side effects have been reported in women taking 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),
• a rash with circular redness or ulcers (erythema multiforme).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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 Klimedix

The medicine should be stored 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 the month. There are no special precautions for storage of the medicinal product. Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

• The active substances of Klimedix are estradiol and drospirenone. Each coated tablet contains 1 mg of estradiol (as 1.03 mg of estradiol hemihydrate) and 2 mg of drospirenone.
• Other ingredients are: Tablet coating:Polyvinyl alcohol Titanium dioxide (E 171) Macrogol 3350 Talc Soy lecithin

Tablet core:Lactose monohydrate Corn starch Pregelatinized corn starch Povidone K-25 Magnesium stearate

What Klimedix looks like and what the packaging contains

White or almost white, round, biconvex, coated tablet with a diameter of approximately 6 mm, with "GD3" embossed on one side, the other side is smooth. Klimedix 1 mg + 2 mg coated tablets are packaged in PVC/PVDC//Al blisters. The blisters are packaged in a cardboard box containing a patient leaflet and a case for storing the blisters. Packaging sizes: 28 coated tablets 84 coated tablets Not all packaging sizes may be marketed.

Marketing authorization holder

GEDEON RICHTER POLSKA Sp. z o.o. ul. Ks. J. Poniatowskiego 5 05-825 Grodzisk Mazowiecki

Manufacturer

Gedeon Richter Plc. Gyömrői út 19-21 1103 Budapest Hungary For more information on this medicine and its names in other EU member states, you should contact: GEDEON RICHTER POLSKA Sp. z o.o. Medical Department ul. ks. J. Poniatowskiego 5 05-825 Grodzisk Mazowiecki tel. +48 (22)755 96 48 lekalert@grodzisk.rgnet.org fax: +48 (22) 755 96 24

Date of last revision of the leaflet: October 2020

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