Klimonorm, 21 pcs.

Pharmgroup:

The anti-climacteric (estrogen+gestagen).

Pharm action:

Climonorm contains estrogen – estradiol valerate, which is converted in the human body into natural 17β-estradiol. Klimonorm also contains a 19-nortestosterone derivative, levonorgestrel. The addition of levonorgestrel for 12 days of each cycle reduces the risk of endometrial hyperplasia and cancer.

Because of the composition and the cyclic pattern of taking Climonorm, (taking only estrogen for 9 days, then a combination of estrogen and gestagen for 12 days, and finally a 7-day break), women with a failed uterus have a menstrual cycle when taking the drug regularly.

Estradiol replenishes estrogen deficiency in the female body after menopause and provides effective treatment of psycho-emotional and vegetative menopausal 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 skin and mucous membranes, especially mucous membranes of the genitourinary system (urinary incontinence, dryness and irritation of the vaginal mucosa, painfulness during sexual intercourse).

Estradiol prevents loss of bone mass caused by estrogen deficiency. Mainly it is connected with suppression of function of osteoclasts and shift of process of bone remodeling towards bone formation. Long-term use of hormone replacement therapy (HRT) has been shown to reduce the risk of periprosthetic bone fractures in postmenopausal women. The rate of decline in bone mass is comparable to that seen in the immediate postmenopausal period when MHT is withdrawn. It has not been shown that using MHT can restore bone mass to premenopausal levels.

HGT also has beneficial effects on the collagen content of the skin, as well as skin density, and can also slow the formation of wrinkles.

The intake of Climonorm leads to a decrease in total cholesterol, low-density lipoproteins (LDL) and an increase in high-density lipoproteins (HDL), resulting in a significant increase in the HDL/LDL ratio as well as an increase in triglycerides.
Observational studies suggest that the incidence of colorectal cancer decreases among postmenopausal women when MST is used. The mechanism of action is still unclear.

Pharmacokinetics:

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

Levonorgestrel is quickly and almost completely absorbed from the gastrointestinal tract after oral administration. Maximum concentration in blood serum is reached after 1-2 hours. 93-95% of levonorgestrel is bound to albumin and globulin binding sex hormones (GSSH). Metabolites of levonorgestrel are excreted with urine and bile, mainly as sulfates and glucuronides.

Indications

Active ingredient

Composition

1 yellow colored tablet contains:

Active ingredient:

Estradiol valerate 2 mg;

Associates:

iron oxide yellow,

purified water,

carnauba wax,

dextrose (glucose),

gelatin,

calcium carbonate,

potato starch,

/p>

lactose monohydrate,

magnesium carbonate basic,

magnesium stearate,

macrogol 35,000,

povidone K25,

sucrose,

talc,

titanium dioxide.

1 brown colored dragee contains:

Active substance:

estradiol valerate 2 mg,

levonorgestrel 0.15 mg;

Associates:

iron oxide brown,

iron oxide red,

purified water,

p> carnauba wax,

dextrose (glucose),

gelatin,

calcium carbonate,

potato starch,

lactose monohydrate,

magnesium hydroxycarbonate basic,

magnesium stearate,

macrogol 35,000,

povidone K25,

How to take, the dosage

Klimonorm is taken orally, the pills are swallowed whole with a small amount of liquid. The time of day when a woman takes Klimonorm does not matter, but if she started to take the pills at a particular time, she must keep to that time. If the woman forgets to take the pills, she can take them within the next 12-24 hours. If treatment is interrupted for a longer time, vaginal bleeding may occur.

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

Each pack is designed to be taken for 21 days. One yellow pill is taken daily for the first 9 days and then one brown pill daily for 12 days. After 21 days of taking the drug, a 7-day break in administration follows, during which menstrual-like bleeding occurs, caused by withdrawal of the drug (usually on the 2nd or 3rd day after taking the last dragee).

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

Interaction

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

Special Instructions

Climonorm is not used for the purpose of contraception.

Before starting or resuming on ZGT, it is recommended that a woman undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical mucus), to rule out pregnancy. In addition, clotting disorders should be excluded. Periodic follow-up examinations should be performed.

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

In the presence or worsening of any of the following conditions or risk factors, the individual risk-benefit ratio of treatment should be evaluated before starting or continuing on ZGT.

Venous thromboembolism

A number of controlled randomized as well as epidemiologic studies have found an increased relative risk of venous thromboembolism (VTE) with ZGT, i.e., deep vein thrombosis or pulmonary embolism. Therefore, when prescribing MHT to women with risk factors for VTE, the risk-benefit ratio of treatment must be carefully weighed and discussed with the patient.

Risk factors for VTE include individual and family history (the presence of VTE in immediate family members at a relatively young age may indicate a genetic predisposition) and severe obesity. The risk of VTE also increases with age. 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, the appropriateness of temporarily discontinuing VTE should be considered.

Stop treatment immediately if symptoms of thrombotic disorders appear or are suspected.

Arterial thromboembolism

In randomized controlled trials, there has been no evidence of cardiovascular benefit with long-term use of combined conjugated estrogens and medroxyprogesterone acetate. In large-scale clinical trials of this compound, a possible increased risk of coronary disease in the first year of use was found. An increased risk of stroke has also been found. To date, no long-term randomized controlled trials have been conducted with other MHT drugs to find a beneficial effect on cardiovascular morbidity and mortality. Therefore, it is not known whether this increased risk extends to MHT drugs containing other types of estrogens and progestagens.

Endometrial cancer

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

Breast cancer

In clinical trials and observational studies, an increase in the relative risk of developing breast cancer has been found in women who have been on ZHT for several years. This may be due to earlier diagnosis, the biological effects of MHT, or a combination of both. The relative risk increases with duration of treatment (by 2.3% for a year), perhaps even more so when estrogen is combined with progestogens. This increase is comparable to the increased risk of breast cancer in women with each year of delayed natural menopause (by 2.8% per year of delay) and with obesity and alcohol abuse. The increased risk gradually declines to normal levels during the first 5 years after cessation of MHT.

Breast cancer detected in women receiving MHT tends to be more differentiated than in women not receiving it, according to studies.

MST increases mammographic breast density, which in some cases may have a negative impact on radiological detection of breast cancer.

Hepatic tumors

In the background of using sex steroids, which include MHT, benign and even rarer malignant liver tumors have been observed in rare cases. In some cases these tumors have resulted in life-threatening intraperitoneal bleeding. If there is upper abdominal pain, an enlarged liver, or signs of intraperitoneal bleeding, the possibility of a liver tumor should be considered in the differential diagnosis.

Biliary stone disease

Oestrogens are known to increase the lithogenicity of bile. Some women are predisposed to develop gallstone disease when treated with estrogen.

Other conditions

The treatment should be stopped immediately if migraine-like or frequent and unusually severe headaches occur for the first time, or if other symptoms – possible precursors of a thrombotic cerebral stroke – occur.

The relationship between MHT and the development of clinically significant arterial hypertension has not been established. Small increases in BP have been described in women receiving MHT, and clinically significant increases are rare. However, in some cases, if persistent clinically significant arterial hypertension develops on ZGT, discontinuation of ZGT may be considered.

In non-serious liver function disorders, including various forms of hyperbilirubinemia such as Dubin-Johnson syndrome or Rotor syndrome, monitoring by a physician is necessary, as well as periodic liver function tests. If liver function worsens, ZHT should be stopped.

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

Women with moderately elevated TG levels require special monitoring. In such cases, the use of MHT may cause further increases in TG levels in the blood, which increases the risk of developing acute pancreatitis.

While MHT can affect peripheral insulin resistance and glucose tolerance, there is usually no need to change a diabetic’s treatment regimen with MHT. However, diabetic patients who are on MHT require monitoring.

Some patients may develop adverse effects of estrogen stimulation, such as abnormal uterine bleeding, under the influence of ZGT. Frequent or persistent abnormal uterine bleeding after treatment is an indication for endometrial exploration.

If treatment of irregular menstrual cycles fails, it may be necessary to screen for organic disease.

Estrogen may cause an increase in the size of the uterine myoma. If this occurs, treatment should be stopped.

Stop treatment is recommended if recurrent endometriosis occurs with ZHT.

If prolactinoma is suspected, this condition should be ruled out before starting treatment.

In some cases, chloasma may occur, especially in women with a history of pregnancy chloasma. Women with a history of chloasma should avoid prolonged exposure to the sun or UV radiation while on MHT.

The following diseases and conditions may occur or worsen on MHT: epilepsy, benign breast tumor, bronchial asthma, migraine, porphyria, otosclerosis, systemic lupus erythematosus, minor chorea. Although these diseases and conditions have not been proven to be associated with MHT, such patients should be monitored by a physician during MHT.

Impact on laboratory results

Introduction of sex steroids Taking sex steroids may affect biochemical measures of liver, thyroid, adrenal, and renal function, plasma levels of transport proteins such as corticosteroid-binding globulin and lipid/lipoprotein fractions, and measures of carbohydrate metabolism, coagulation, and fibrinolysis.

Influence on the ability to drive and operate machinery

No effect.

Contraindications

Side effects

Gastrointestinal system disorders: during the first cycles of treatment, gastrointestinal disorders, nausea, vomiting are possible.

Urogenital system disorders: irregular, increased and prolonged vaginal bleeding.

Skin disorders: skin pigmentation (chloasma), itching.

Others: soreness of the mammary glands, weakening of libido.

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Overdose

Acute toxicity studies have shown no risk of acute side effects when Klimonorm is taken accidentally in amounts many times greater than the daily therapeutic dose.

Symptoms: nausea, vomiting, vaginal bleeding are possible.

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