Klimonorm, pills, 21pcs

Composition

1 yellow dragee contains:

Active ingredient:

estradiol valerate 2 mg;

Auxiliary substances:

yellow iron oxide,

purified water,

Carnauba wax,

dextrose (glucose),

gelatin,

calcium carbonate,

potato starch,

lactose monohydrate,

magnesium carbonate basic,

magnesium stearate,

macrogol 35 000,

povidone K25,

sucrose,

talc,

titanium dioxide.

1 brown dragee contains:

Active ingredient:

estradiol valerate 2 mg,

levonorgestrel 0.15 mg;

Auxiliary substances:

iron oxide brown,

iron oxide red,

purified water,

Carnauba wax,

dextrose (glucose),

gelatin,

calcium carbonate,

potato starch,

lactose monohydrate,

magnesium hydroxycarbonate basic,

magnesium stearate,

macrogol 35 000,

povidone K 25,

sucrose,

talc,

titanium dioxide.

Pharmacological action

Pharmaceutical group:

anti-climacteric agent (estrogen+progestogen).

Pharmaceutical action:

 Klimonorm contains estrogen-estradiol valerate, which in the human body is converted to natural 17b-estradiol. Also, the composition of the drug Klimonorm includes a derivative of 19-nortestosterone-levonorgestrel. Levonorgestrel supplementation for 12 days of each cycle reduces the risk of endometrial hyperplasia and cancer.

Due to the composition and cyclical scheme of taking Klimonorm (taking only estrogen for 9 days, then a combination of estrogen and progestogen for 12 days, and finally a 7 – day break), women with a non-removed uterus with regular use of the drug establish a menstrual cycle.

Estradiol makes up for the lack of estrogens in the female body after menopause and provides effective treatment for psycho-emotional and vegetative climacteric symptoms (such as hot flashes, increased sweating, sleep disorders, increased nervous excitability, irritability, palpitations, cardialgia, dizziness, headache, decreased libido, muscle and joint pain); involution of the skin and mucous membranes, especially the mucous membranes of the genitourinary system (urinary incontinence, dryness and irritation of the vaginal mucosa, soreness during sexual intercourse).

Estradiol prevents bone loss caused by estrogen deficiency. This is mainly due to the suppression of osteoclast function and a shift in the process of bone remodeling towards bone formation. Long-term use of hormone replacement therapy (HRT) has been shown to reduce the risk of peripheral bone fractures in women after menopause. When HRT is discontinued, the rate of bone loss is comparable to that observed immediately after menopause. It has not been proven that HRT can restore bone mass to pre-menopausal levels.

HRT also has a beneficial effect on the collagen content of the skin, as well as its density, and can also slow down the formation of wrinkles.

Taking Klimonorm leads to a decrease in total cholesterol, low-density lipoproteins (LDL) and an increase in high-density lipoproteins( HDL), resulting in a significantly increased HDL ratio/LDL, as well as increased triglyceride levels. Observational studies suggest that among postmenopausal women, the incidence of colon cancer decreases when HRT is used. The mechanism of action is still unclear.

Pharmacokinetics:  

After oral use, estradiol valerate is rapidly and completely absorbed from the gastrointestinal tract (GIT). After entering the body, it is rapidly metabolized to form 17b-estradiol and estrone, which then undergo standard metabolic transformations. After oral use, about 3% of estradiol becomes bioavailable. The maximum concentration of estradiol is reached in 2-3 hours, the estrone-estradiol ratio is 4: 1. Estradiol is excreted as metabolites, mainly in the urine (90%) and, to a lesser extent, with bile.

After oral use, levonorgestrel is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in the blood serum is reached in 1-2 hours. 93-95% of levonorgestrel binds to albumin and sex hormone-binding globulin (SHBG). Levonorgestrel metabolites are excreted in the urine and bile, mainly in the form of sulfates and glucuronides.

Indications

• of hormone replacement therapy in pre – and postmenopausal women, including after surgical removal of the ovaries;
• atrophy of the skin and mucous membranes (including reproductive organs) in postmenopausal women;
• menopausal syndrome (mental and autonomic) symptoms in peri – and postmenopausal women;
• signs of irritation of the bladder and urethra, urinary incontinence in a stressful situation (atrophy of the sphincter of the bladder) in postmenopausal women;
• prevention of postmenopausal osteoporosis.

Contraindications

• Hypersensitivity to Klimonorm;
• severe dysfunction and liver tumors (including in the anamnesis);
• congenital disorders of lipid metabolism;
• thromboembolic processes (including in the anamnesis);
• myocardial infarction;
• acute ischemic stroke;
• hormone-dependent tumors of the uterus, ovaries and mammary glands or suspicion of them;
• endometriosis and abnormal genital bleeding;
• diabetes mellitus (severe form), diabetic angiopathy;
• idiopathic jaundice, pruritus, herpes, progressive otosclerosis during pregnancy

Side effects

From the digestive tract: during the first treatment cycles, gastrointestinal disorders, nausea, vomiting are possible.

From the genitourinary system: irregular, increased and prolonged vaginal bleeding.

From the skin: pigmentation on the skin (chloasma), itching.

Other: breast tenderness, decreased libido.

Interaction

The activity is reduced by drugs that accelerate the biotransformation of steroid hormones: barbiturates, non-narcotic analgesics (phenylbutazone), antibiotics (rifampicin, ampicillin, tetracycline, griseofulvin), antiepileptic drugs (carbamazepine, phenytoin).

How to take, course of use and dosage

Klimonorm is taken orally, pills are swallowed whole, washed down with a small amount of liquid. The time of day when a woman takes Climonorm does not matter, however, if she started taking pills at any particular time, she should continue to stick to this time. If a woman has forgotten to take a tablet, she can take it within the next 12-24 hours. If treatment is interrupted for a longer period of time, vaginal bleeding may occur.

If the patient is still menstruating, treatment should begin on the 5th day of the menstrual cycle (the 1st day of menstrual bleeding corresponds to the 1st day of the menstrual cycle).

Each package is designed for a 21-day reception. One yellow tablet is taken daily for the first 9 days, and then one brown tablet is taken daily for 12 days. After 21 days of taking the drug, there is a 7-day break in the intake, during which menstrual-like bleeding occurs, caused by the withdrawal of the drug (usually 2-3 days after taking the last tablet).

After a 7-day break in taking the drug, a new package of Klimonorm is started, taking the first tablet on the same day of the week as the first tablet from the previous package.

Overdose

Studies of acute toxicity have not revealed the risk of acute side effects when accidentally taking the drug Klimonorm in an amount many times higher than the daily therapeutic dose.

Symptoms:  possible nausea, vomiting, and vaginal bleeding.

Treatment:  there is no specific antidote, and the treatment is symptomatic.

Special instructions

Klimonorm is not used for the purpose of contraception.

Before starting or resuming HRT, a woman is recommended to undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical mucus), to exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. Follow-up examinations should be carried out periodically.

If contraception is necessary, non-hormonal methods should be used (with the exception of calendar and temperature methods). If pregnancy is suspected, you should stop taking pills until pregnancy is ruled out.

If any of the following conditions or risk factors are present or worsen, the individual risk-benefit ratio should be evaluated before starting or continuing HRT.

Venous thromboembolism

A number of controlled, randomized, and epidemiological studies have identified an increased relative risk of developing venous thromboembolism (VTE) with HRT, i. e. deep vein thrombosis or pulmonary embolism. Therefore, when prescribing HRT to women with VTE risk factors, the risk-benefit ratio of treatment should be carefully weighed and discussed with the patient.

Risk factors for VTE include an individual and family history (the presence of VTE in close relatives at a relatively young age may indicate a genetic predisposition) and severe obesity. The risk of VTE also increases with age. The question of the possible role of varicose veins in the development of VTE remains controversial.

The risk of VTE may temporarily increase with prolonged immobilization, extensive elective and trauma surgeries, or massive trauma. Depending on the cause or duration of immobilization, a decision should be made on whether to temporarily stop HRT.

Treatment should be stopped immediately if symptoms of thrombotic disorders appear or if they are suspected to occur.

Arterial thromboembolism

In randomized controlled trials, long-term use of combined conjugated estrogens and medroxyprogesterone acetate did not provide evidence of a positive effect on the cardiovascular system. In large-scale clinical trials of this compound, a possible increase in the risk of coronary disease in the first year of use was identified. An increased risk of stroke was also found. To date, no long-term randomized controlled trials have been conducted with other HRT drugs to identify a positive effect on morbidity and mortality rates related to the cardiovascular system. Therefore, it is not known whether this increased risk extends to HRT medications containing other types of estrogens and progestogens.

Endometrial cancer

Long-term estrogen monotherapy increases the risk of developing endometrial hyperplasia or carcinoma. Studies have confirmed that the addition of progestogens reduces the risk of endometrial hyperplasia and cancer.

Breast cancer

According to clinical trials and observational studies, an increase in the relative risk of breast cancer was found in women who received HRT for several years. This may be due to an earlier diagnosis, the biological effect of HRT, or a combination of both. The relative risk increases with increasing duration of treatment (by 2.3% when used for a year), possibly even more when combined with estrogens and progestogens. This increase is comparable to the increase in the risk of breast cancer in women with each year of delay in the onset of natural menopause (by 2.8% per year of delay), as well as with obesity and alcohol abuse. The increased risk gradually decreases to normal levels during the first 5 years after stopping HRT.

According to research, breast cancer detected in women who receive HRT is usually more differentiated than in women who do not receive it.

HRT increases mammographic density of the mammary glands, which in some cases can have a negative impact on the X-ray detection of breast cancer.

Liver tumors

Against the background of the use of sex steroids, which also include HRT products, in rare cases benign, and even less often malignant liver tumors were observed. In some cases, these tumors have resulted in life-threatening intraperitoneal bleeding. If there is pain in the upper abdomen, an enlarged liver, or signs of intraperitoneal bleeding, the differential diagnosis should take into account the likelihood of a liver tumor.

Cholelithiasis

Estrogens are known to increase the lithogenicity of bile. Some women are predisposed to developing cholelithiasis when treated with estrogens.

Other states

Treatment should be stopped immediately if migraine-like or frequent and unusually severe headaches occur for the first time, as well as if other symptoms appear – possible harbingers of a thrombotic stroke of the brain.

The relationship between HRT and the development of clinically pronounced arterial hypertension has not been established. In women receiving HRT, a slight increase in blood pressure has been described, but clinically significant increases are rare. However, in some cases, if persistent clinically significant arterial hypertension develops while taking HRT, discontinuation of HRT may be considered.

In cases of mild hepatic impairment, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, it is necessary to monitor the doctor, as well as periodic studies of liver function. If liver function indicators worsen, HRT should be discontinued.

If there is a relapse of cholestatic jaundice or cholestatic pruritus observed for the first time during pregnancy or previous treatment with sex steroid hormones, HRT should be stopped immediately.

Special monitoring is needed for women with moderately elevated TG levels. In such cases, the use of HRT can cause a further increase in the level of TG in the blood, which increases the risk of developing acute pancreatitis.

Although HRT can affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the treatment regimen for patients with diabetes mellitus during HRT. Nevertheless, patients with diabetes mellitus should be monitored for HRT.

Some patients may develop undesirable manifestations of estrogen stimulation, such as abnormal uterine bleeding, under the influence of HRT. Frequent or persistent abnormal uterine bleeding during treatment is an indication for endometrial examination.

If treatment of irregular menstrual cycles does not give results, an examination should be performed to exclude organic diseases.

Under the influence of estrogens, an increase in the size of uterine fibroids is possible. In this case, treatment should be discontinued.

It is recommended to stop treatment if a relapse of endometriosis develops on the background of HRT.

If the presence of prolactinoma is suspected, this disease should be excluded before starting treatment.

In some cases, chloasma may occur, especially in women with a history of pregnancy chloasma. During HRT, women with a tendency to develop chloasma should avoid prolonged exposure to the sun or UV radiation.

The following diseases and conditions may occur or worsen with HRT: epilepsy, benign breast cancer, bronchial asthma, migraine, porphyria, otosclerosis, systemic lupus erythematosus, chorea minor. Although the association of these diseases and conditions with HRT has not been proven, such patients should be under the supervision of a doctor during HRT.

Influence on the results of laboratory tests

The use of sex steroids can affect the biochemical parameters of liver, thyroid, adrenal and kidney function, the content of transport proteins in plasma, such as corticosteroid-binding globulin and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis.

Influence on the ability to drive motor vehicles and manage mechanisms

It doesn’t affect you.

Form of production

Dragees

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

5 years

Active ingredient

Levonorgestrel, Estradiol

Conditions of release from pharmacies

By prescription

Dosage form

dragees

Purpose

For women, Adults as prescribed by a doctor, For women in the menopausal period, For postmenopausal women

Indications

Menstrual disorders, Menopause