KLIMONORM 21 tablets

Klimonorm

Coated tablets

Drugs: estradiol valerate and Ievonorgestrel

9 yellow tablets, each containing: estradiol valerate 2.00 mg (equivalent to 1.53 mg estradiol)

12 brown tablets, each containing: estradiol valerate 2.00 mg (equivalent to 1.53 mg estradiol) Ievonorgestrel 0.15 mg

Excipients:

Each yellow tablet contains:

lactose monohydrate; sucrose; glucose liquid; gelatin, potato starch; talc; magnesium stearate; magnesium carbonate, light; calcium carbonate; povidone K 25 ;, macrogol 35,000; carnauba wax; titanium dioxide (E 171); ferric hydroxide (E 172)

Each brown tablet contains lactose monohydrate, sucrose, glucose liquid, gelatin, potato nishaste, talc, magnesium stearate; magnesium carbonate, light; calcium carbonate; povidone K 25 ;, macrogol 35,000; wax; titanium dioxide (E 171); iron (III) oxide (E 172); ferric hydroxide (E 172); iron oxides and iron hydroxides (E 172)

Klimonorm is provided in packages containing one blister of 21 coated tablets.

1. What is Klimonorm and what is it used?

1.1 Klimonorm is a combination of two female sex hormones (estrogen and progestogen) for a combination, cyclic (available from tablets intervals) hormone replacement therapy (HRT).

1.3 Klimonorm shown HRT for symptoms of deficiency of female sex hormones (estrogens) in women just before or after their last menstrual period (menopause); prevention of increased loss of bone tissue after the last normal menstruation (postmenopausal osteoporosis) in women who are at high risk of future fractures who are intolerant of or are contraindicated for treatment with other medicinal products intended for the prevention of osteoporosis . The experience of treating women older than 65 years is limited.

2. Before use Klimonorm

2.1 Klimonorm must be taken:

if you are allergic to estradiol valerate, Ievonorgestrel or any of the excipients of Klimonorm;

- If you suffer or have suffered from breast cancer or suspected breast cancer;

- If you have estrogen-dependent malignant tumors or in case of doubt (eg. Cancer of the uterus);

- If you have vaginal bleeding, the cause for which your doctor can detect;

- If your uterine mucosa is increased growth which was not treated (untreated endometrial hyperplasia);

- If you have ever suffered or are suffering from venous gromboembolizam (deep vein thrombosis, eg. Blood clot in a deep vein, pulmonary embolism);

- If you have or have recently developed arterial thromboembolic disease (such as angina pectoris, myocardial infarction);

- If you suffer from severe liver disease or had evidence of liver disease in the past to return to liver function tests the norm;

- If you have porphyria (a metabolic disease affecting the formation of red blood pigment).

2.2 Special precautions for use of Klimonorm

Medical examination / follow

Before initiating or reinstituting HRT should lift the complete medical and family history. By this and by the contraindications and warnings for use must take a physical examination (including pelvic and breast). During treatment periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse. They must be made Investigations, including mammography, in accordance with currently accepted screening practices, modified to the clinical needs of the patient. It is necessary to carefully assess the risk / benefit for the period in which women are subjected to HZT.Klimonorm not suitable for contraception.

Conditions requiring monitoring

The patient should be monitored if has appeared and / or exacerbation any of the following conditions during pregnancy or previous hormone treatment. It should be taken into account that these conditions may recur or be aggravated during treatment with Klimonorm, particularly in:

• leiomyomata (uterine fibroids), or endometriosis (when the mucosal tissue of the uterus is found outside the uterus), history of or risk factors for thromboembolic disorders (see below) risk factors for estrogen-dependent tumors, i.e. 1st degree heredity breast cancer hypertension, liver disease (eg. Hepatic adenoma - a benign tumor "liver)

'■ diabetes mellitus with or without vascular complications

- Holilitiaza (gallstones)

• migraine or (severe) headache

• systemic lupus erythematosus, an autoimmune disease type

• evidence of excessive growth of the uterine lining (endometrial hyperplasia), (see below)

• epilepsy

• Asthma

• otosclerosis

Reasons for immediate withdrawal of therapy

Therapy should be discontinued in case a contraindication is openly referred to in 2.1 Klimonorm should not be taken :, and in the following cases:

• jaundice or deterioration of liver function

• a significant increase in blood pressure

• a new bout of migraine-type headache

• pregnancy

Changes in the uterine lining (endometrium)

The risk of excessive growth of the uterine lining (endometrial hyperplasia) and cancer increases when estrogen is taken alone without additional progestogen dose for an extended period of time. To reduce the risk (which does not eliminate it completely) necessary estrogen therapy can be combined with a progestogen for at least 12 days per cycle in women with a uterus. Klimonorm contains that progestogen in 12 brown tablets. Unexpectedly, but usually slight bleeding may occur during the first months of treatment. It is necessary to carefully track any breakthrough bleeding or spotting while taking Klimonorm. If irregular bleeding continues longer need to contact your doctor. The reasons should be clarified by your doctor if the irregular bleeding continues after treatment or after termination. This may include an endometrial biopsy (examination of tissue from the lining of the uterus) to exclude endometrial tumor formation.

Breast cancer

An increased risk of breast cancer in women taking estrogens, combinations of estrogen and progestogen HRT for several years reported clinical and epidemiological studies (see also 4. Possible side effects). This risk increases with duration of intake but returns to normal within about five years after stopping treatment. Women using estrogen-progestogen combined HRT had a similar or possible higher risk compared to women who take estrogen-only.

Venous thromboembolism

HRT is associated with a higher relative risk of developing venous thromboembolism (VTE;: risk of blockage of veins by a blood clot, like deep vein thrombosis. The results of a clinical and epidemiological study showed two to three times higher risk for these that users compared with those that do not carry such. In women users it is estimated that the number of cases of VTE that will occur over a 5 year period is about 3 per 1000 women aged 50 -59 years and 8 per 1000 women aged 60-69 years. It has been found that in healthy women who use HRT for five years, the number of additional cases of VTE will be between 2 and 6 (best estimate = 4) per 1000 women aged 50-59 years and between 5 and 15 (best estimate - 9) of 1000 women aged 60-69 years. The emergence of such a thromboembolic event is more likely in the first year of HRT than later.

Generally recognized risk factors for VTE include:

• personal history of venous thromboembolism

• a family history of venous thromboembolism

• severe obesity (BMI> 30 kg / m2) and

• systemic lupus erythematosus, an autoimmune disease type.

There is no consensus about the possible role of varicose veins in VTE. Patients with a history of VTE or already taking drugs for disorders of blood clotting (anticoagulants) require careful consideration of the risk / benefit ratio. Data from personal data or strong family history of thromboembolism or recurrent spontaneous abortion should be investigated to exclude predisposition to the formation of blood clots (thrombosis). While a definite diagnosis or while initiating treatment with anticoagulants, use of HRT in such patients should be viewed as contraindicated. The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or surgery. As with all patients in the postoperative period, it should pay attention to prophylactic measures to prevent VTE following surgery. When surgery is followed by prolonged immobilization, particularly abdominal or orthopedic surgery of the lower limbs, consideration should be given to temporarily stopping HRT 4 to 6 weeks earlier, if possible. Therapy should not be restarted until the woman is completely mobilized. If VTE develops after initiating therapy, the drug should be discontinued. If you experience a painful swelling of the legs sudden chest pain or difficulty breathing should inform your doctor.

Ischemic heart disease

There are no data from randomized controlled clinical trials beneficial effects on the cardiovascular system in continuous combined HRT (including conjugated estrogens and medroxyprogesterone acetate). Large clinical trials showed a possible increased risk of cardiovascular morbidity in the first year of use and no overall benefit. For other HRT products whose lekarstveni_veshtestva differ from those mentioned above, there are no data from clinical trials examining effects in cardiovascular morbidity or mortality.

Therefore, it can certainly be said that these results apply to other HRT products.

Stroke

A large clinical study indicates an increased risk of stroke in healthy women during continuous combined conjugated oestrogens and progestogen medroxyprogesterone acetate:

For women who are not using HRT, it was found that the number of cases of stroke that will occur over a period of 5 years is about 3 per 1000 women aged 50-59 years and 11 per 1000 women aged 60-69 years.

It is estimated that women who use conjugated estrogens for five years, the number of additional cases will be between 0 and 3 (best estimate = 1) of 1000 users aged 50-59 years and between 1 and 9 ( best estimate = 4) per 1000 users aged 60-69 years. It is unknown whether the increased risk is attributable to other HRT products.

Ovarian carcinoma

Long-term (less than 5-10 years) use of HRT products containing only estrogen in hysterectomised women (surgically removed uterus), in some epidemiological studies to be associated with an increased risk of ovarian cancer. It is not known whether the continuous combined HRT is the reason for difference in risk compared to estrogen-only products.

Liver diseases

In rare cases, benign and even more rarely malignant liver tumors following the use of hormones such as those contained in Klimonorm. In isolated cases, these tumors led to life-threatening intra-abdominal haemorrhage. If you are experiencing sharp pain in the upper abdomen, enlarged liver or signs of intra-abdominal haemorrhage it must be borne in mind and liver tumor in the differential diagnosis.

Biliary disease

There is an increased risk of gallbladder disease in women taking estrogen during menopause or called. "Change of life".

Other diseases

Estrogens may cause fluid retention and therefore patients with cardiac or renal failure should be monitored. Patients with terminal renal insufficiency should be closely observed, since it is expected to increase the level of circulating active ingredients in Klimonorm. Women suffering from a specific disease lipometabolitno (hypertriglyceridemia) must be under control during estrogen replacement or hormone replacement therapy, since there are reports of isolated cases of significant increase in blood fats (triglycerides) leading to pancreatitis during treatment with estrogen.

Interference with laboratory tests

Administration of this product may affect certain laboratory tests: Estrogens can increase the level in the blood plasma of the binding proteins of thyroid hormones (thyroxine binding globulin, TBG), resulting in a change in functional laboratory tests of thyroid (incl. An increase of total circulating thyroid hormone. Certain thyroid hormones are unchanged (free T4 and CA) .Drugi binding proteins may be elevated in serum, ie corticoid binding hormone (CBG) and sex hormone binding globulin (SHBG). Other plasma proteins may be increased (angiotensinogen / renin substrate, alpha-1-antitrypsin, ceruloplasmin).

Children

Klimonorm is not indicated for use in children.

Elderly women

Does not require extra precautions and special dosage in elderly women.

Pregnancy

Klimonorm should not be used in pregnancy. If you become pregnant during therapy with Klimonorm should immediately stop taking it. The results of most epidemiological studies to date, providing information on inadvertent fetal exposure to combinations of estrogens with other progestogens do not indicate teratogenic or foetotoxic effect.

Breastfeeding

Klimonorm is not indicated for use during lactation. Before you start taking any medicine ask your doctor or pharmacist.

Driving and using machines

No special measures.

2.3 Interaction with other medicinal products

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even if these are drugs that are not on prescription.

• Reduce effects of Klimonorm

Concomitant use of certain medications such as anticonvulsants (phenobarbital, phenytoin, carbamazepine) and anti-infectives (rifampicin, rifabutin, nevirapine, efavirenz) can accelerate hepatic metabolism of hormones by the so-called. enzyme induction and affect the effectiveness of Klimonorm.

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast - exhibit inducing properties when used concomitantly with steroid hormones such as estrogens and progestogens. Herbal products containing St. John's wort (Hypericum Perforatum) may induce the metabolism of estrogens and progestogens. Clinically, an increased metabolism of estrogens and progestogens may lead to decreased effect and changes in the uterine bleeding.

• Other possible interactions

The need for oral antidiabetics or insulin can be changed as a result of the effect on glucose tolerance. Some laboratory tests may be influenced by estrogen, such as functional tests of the thyroid gland (see 2.2 Special warnings for use of Klimonorm / Influence on laboratory tests) or glucose tolerance tests.

3. How and when to accept Klimonorm?

Always take Klimonorm exactly as prescribed by your doctor. If you are unsure, ask your doctor or pharmacist. To treat your menopausal symptoms, your doctor will try to stabilize your lowest effective dose and will continue treatment as long as the benefits prevail over risks. Please tell your doctor if you think that the effect of Klimonorm is too weak or too strong.

3.1. How to take Klimonorm?

Medicinal product is for oral administration. The tablets should be swallowed with a sufficient amount of liquid at the same hour of the day, preferably at night, in order to reduce the gastrointestinal problems.

3.2 Unless otherwise prescribed by your doctor generally dose is:

A yellow tablet is considered the first nine days, followed by a brown tablet for the remaining twelve days. Take the first yellow tablet from the field marked with number 1. Follow the arrow next tablet. Once finished tablets three weeks following a 7-day tablet-free period. During this period, it should appear normal bleeding, similar to menstruation. After 7-day pause continue taking tablets from the next package, regardless of whether bleeding has stopped or continued. The first day of admission after the pause should always be the same day of the week when you started therapy. .