Instructions for use CLIMEN

Compound

Special instructions for the use of the drug Klimen

Clymene is not used as a contraceptive. If necessary, use non-hormonal methods of contraception, with the exception of calendar and temperature. If pregnancy is suspected, the drug should be discontinued until pregnancy is completely excluded. Before starting HRT, the following conditions/risk factors should be taken into account when assessing the risk/benefit of treatment, taking into account the individual characteristics of each patient. The use of HRT should be stopped immediately if any of the contraindications are identified, as well as in the presence of the following conditions and diseases:

• migraine-like or frequent and unusually severe headaches appearing for the first time, or other symptoms that are likely prodromal signs of cerebral vascular occlusion;
• recurrence of cholestatic jaundice or cholestatic pruritus first noted during pregnancy or previous use of sex steroids;
• symptoms of thrombotic disorders or suspicion of their occurrence.

In the event of a relapse or exacerbation of any of the following diseases or risk factors, it is recommended to repeat an individual analysis of the balance of benefits and risks of therapy, taking into account the possible need to discontinue treatment. Venous thromboembolism (VTE) The results of epidemiological and randomized controlled studies suggest an increase in the relative risk of developing VTE, that is, deep vein thrombosis, or pulmonary embolism. As a result, when consulting when prescribing HRT for women with a risk factor for developing VTE, the risk-benefit ratio of the treatment should be carefully weighed. Generally recognized risk factors for the development of VTE include: personal and family history (a case of VTE in a close relative at a relatively early age may indicate a genetic predisposition), 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, after major elective or emergency surgery, or after severe trauma. The issue of temporary cessation of HRT should be decided depending on the nature of the surgical intervention and the duration of immobilization. Arterial thromboembolism The results of two clinical studies using a combination of conjugated equine estrogens and medroxyprogesterone acetate (MPA) in a continuous regimen indicate a possible increase in the risk of developing coronary artery disease during the first year of their use; subsequently, with continued treatment, the risk remains constant. Results from a clinical trial showed a potential reduction in the incidence of coronary artery disease in women aged 50–59 years who received estrogen monotherapy. Another negative factor was a 30–40% increase in the risk of stroke with estrogen monotherapy or their use in combination with MPA. Gallstone disease Estrogens increase the lithogenicity of bile. Some women have been shown to develop a tendency to develop gallbladder disease during estrogen treatment. Dementia Based on clinical studies using HRT drugs, it has not been proven that taking hormones increases the risk of developing dementia when treating women aged 65 years and older. The risk may be reduced if HRT treatment is started early in menopause. Tumors Breast cancer The results of clinical studies and observations have shown an increased risk of developing breast cancer in women using HRT for several years. The relative risk increases with the duration of treatment and may be lower or unchanged with estrogen monotherapy. It is noted that tumors identified in women using or previously using HRT are characterized by a higher degree of differentiation. HRT increases image density in mammographic examinations, which can in some cases negatively affect the results of diagnosing breast cancer. Endometrial cancer Long-term estrogen monotherapy increases the risk of developing endometrial hyperplasia or carcinoma. It can be assumed that the inclusion of progestogens in the treatment regimen significantly reduces the risk. Liver tumors After the use of hormonal drugs used in HRT, in isolated cases the development of benign, and even less often, malignant liver tumors was noted. In some cases, these tumors caused life-threatening intra-abdominal bleeding. If there is pain in the upper abdomen, an enlarged liver, or signs of intra-abdominal bleeding, the differential diagnosis should take into account the possibility of a liver tumor. Other conditions No general association has been established between the use of HRT and the development of clinical hypertension. A slight increase in blood pressure has been reported in women receiving HRT; clinically significant cases of increased blood pressure have been reported rarely. However, if persistent hypertension develops during HRT in selected cases, discontinuation of HRT should be considered. For minor liver dysfunction, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, patients require careful monitoring, as well as periodic monitoring of liver function. If liver function tests worsen, HRT should be discontinued. Women with moderately elevated TG levels require special monitoring. In such cases, the use of HRT may cause a further increase in TG levels, which threatens the risk of developing acute pancreatitis. Although HRT may affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the therapeutic regimen for diabetic patients using HRT. However, patients with diabetes mellitus should be under constant medical supervision during HRT. Some patients may develop side effects of estrogen stimulation during HRT, such as abnormal uterine bleeding. Frequent or persistent pathological uterine bleeding during treatment is an indication for examination of the condition of the endometrium. If treatment of menstrual irregularities is unsuccessful, the presence of organic diseases must be excluded using appropriate diagnostic methods. Under the influence of estrogens, the size of uterine fibroids can increase. In such circumstances, HRT treatment should be discontinued. It is recommended to discontinue treatment if recurrence of endometriosis is noted during therapy. If you suspect the presence of prolactinoma, before starting treatment, you must exclude the possibility of such a disease. In some cases, chloasma may be noted, especially in women with a history of chloasma during pregnancy. When taking a course of HRT, women predisposed to chloasma should avoid exposure to the sun or ultraviolet radiation. It has been found that the following conditions and diseases may occur or worsen when using HRT. Although it cannot be confidently stated that these changes are associated with HRT, patients taking HRT who have the following diseases should be closely monitored: epilepsy; benign breast tumors; BA; migraine; porphyria; otosclerosis; systemic lupus erythematosus; chorea. Medical examination/consultation Before starting or resuming HRT, a detailed history of the patient should be taken and a physical examination should be performed, taking into account contraindications (see CONTRAINDICATIONS) and precautions (see APPLICATION), repeating periodic observations. The frequency and nature of examinations should be based on existing standards of medical practice, taking into account the individual characteristics of the patient. As a rule, the pelvic organs are subject to examination, including a standard cytological analysis of the cervix, examination of the abdominal cavity, mammary glands, and determination of blood pressure levels. During pregnancy and breastfeeding. HRT is not prescribed during pregnancy and breastfeeding. If pregnancy occurs during treatment with Climen, use of the drug should be discontinued immediately. Epidemiological studies with steroids have not found an increased risk of congenital defects in newborns whose mothers took these types of hormones during pregnancy and have not identified a single case of teratogenicity from accidental use during early pregnancy. Small amounts of sex hormones can be excreted in breast milk. Impact on the ability to drive vehicles and operate machinery: no impact was noted.

Directions for use and doses

Orally, without chewing, with a small amount of liquid, at approximately the same time, 1 tablet per day, starting from the 5th day of the cycle. After finishing taking the drug from 1 calendar pack, take a 7-day break, during which menstrual-like bleeding begins 2–4 days after taking the last pill. If the doctor does not prescribe another therapy, after a 7-day break they begin to take the drug from the next calendar pack. If there is no bleeding during the 7-day break, treatment is continued only after pregnancy has been ruled out.

Contraindications to the use of the drug Klimen

HRT should not be started for any of the following conditions. If any of these conditions occur during HRT, use of the drug should be stopped immediately:

• During pregnancy and breastfeeding;
• vaginal bleeding of unknown etiology;
• diagnosed or suspected breast cancer;
• identified precancerous conditions or malignant tumors that are dependent on sex steroids, or if their presence is suspected;
• diagnosed liver tumors (benign or malignant) or a history of them;
• severe liver disease;
• arterial thromboembolism in the acute stage (for example, myocardial infarction, stroke);
• exacerbation of deep vein thrombosis, current thromboembolic disorders or information about such diseases in the anamnesis;
• severe form of hypertriglyceridemia;
• information about hypersensitivity to the active substances or to any of the components of the drug.

Interactions of the drug Klimen

Treatment with drugs that affect the activity of liver enzymes (for example, some anticonvulsants and antimicrobials) for a long period can increase the clearance of sex hormones and reduce the clinical effectiveness of HRT drugs. Such properties to induce liver enzymes have been identified in hydantins, barbiturates, primidone, carbamazepine and rifampicin. The same properties can be expected for oxcarbazepine, topiramate, felbamate and griseofulvin. Maximum enzyme induction is usually observed no earlier than 2–3 weeks, but may persist for another 4 weeks after discontinuation of the drug. In isolated cases, during concomitant use of certain types of antibiotics (for example, penicillin and tetracycline groups), a decrease in estradiol levels was noted. Substances with a significant tendency to form conjugates (for example, paracetamol) can increase the bioavailability of estradiol by competitively inhibiting conjugation systems during adsorption. In some cases, the need for oral antidiabetic agents or insulin may change due to an effect on glucose tolerance. Interaction with alcohol: Excessive alcohol consumption during HRT therapy may result in increased circulating estradiol levels. Effect on laboratory results: taking sex steroids may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, the level of transport proteins such as sex hormone binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, as well as parameters of coagulation and fibrinolysis.