Klimara
Klimara: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Climara
ATX code: G03CA03
Active ingredient: estradiol (Estradiol)
Manufacturer: Bayer Weimar GmbH & Co. KG (Germany)
Description and photo update: 2018-27-11
Prices in pharmacies: from 1000 rubles.
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Klimara is an anti-climacteric drug with estrogenic action.
Release form and composition
The dosage form of Klimara is a transdermal therapeutic system (TTS), which is an oval patch, which consists of a transparent carrier film and a transparent homogeneous matrix with the active substance (1 TTS in bags, in a carton box, 4 bags and instructions for using Klimara).
Composition for 1 TTS with an area of 12.5 cm 2 (4.5 cm × 3.3 cm) and a release rate of the active substance of 50 μg / day:
- active ingredient: estradiol hemihydrate - 3.9 mg (in terms of estradiol - 3.8 mg);
- auxiliary ingredients: ethyl oleate - 19.25 mg; isopropyl myristate - 9.65 mg; glyceryl monolaurate - 4.8 mg; copolymer of acrylate - 99 mg.
Composition for 1 TTS with an area of 25 cm 2 (6.3 cm × 4.7 cm) and a release rate of the active substance of 100 μg / day:
- active ingredient: estradiol hemihydrate - 7.8 mg (in terms of estradiol - 7.6 mg);
- auxiliary ingredients: ethyl oleate - 19.25 mg; isopropyl myristate - 9.65 mg; glyceryl monolaurate - 4.8 mg; copolymer of acrylate - 99 mg.
Pharmacological properties
Pharmacodynamics
Climara is a skin-attached patch containing 17β-estradiol, which is identical to the endogenous estradiol produced by the female ovaries. A decrease in their function, accompanied by a decrease in estrogen production, causes the development of menopausal syndrome, accompanied by vasomotor-vegetative and organic symptoms. Hormone replacement therapy (HRT) is aimed at relieving these symptoms. Estradiol among all physiological estrogens is the most active and shows the greatest affinity for estrogen receptors.
Estradiol manifests its effect by regulating the transcription of a limited number of genes in estrogen-sensitive target organs - the uterus, hypothalamus, pituitary gland, vagina, urethra, mammary glands, bones (osteoclasts). Penetrating through the cell membrane, it binds with a high degree of affinity to estrogen receptors. After estradiol activates the hormone-receptor complex, it moves to the nucleus, where it binds to a specific sequence of deoxyribonucleic acid (DNA), hormone-sensitive elements, multiplying the transcription of regulated genes. All estrogen-inducible proteins are unknown, as they range from 50 to 100.
In postmenopausal women, estradiol production is significantly reduced. It is synthesized mainly from precursors produced in the adrenal cortex by aromatization with the aromatase enzyme from androstenedione to form estrone, to a lesser extent from testosterone to form estradiol. Estrone is able to be converted to estradiol by the enzyme 17-hydroxysteroid dehydrogenase. Both enzymes are found in the liver and adipose / muscle tissue. The ratio of estradiol to estrone in postmenopausal women is approximately 1 / 5, while in premenopausal this index larger than unity.
Menopausal disorders are compensated by HRT with the use of estrogen in medium transdermal doses of 25 μg and estradiol at a dose of 100 μg per day.
Estrogen, regardless of the route of administration, in the dose required to reduce menopausal symptoms, has a dose-dependent stimulating effect on endometrial proliferation and mitosis. With estrogen monotherapy, the incidence of endometrial hyperplasia increases and thereby the risk of myometrial carcinoma formation increases. For the prevention of endometrial hyperplasia, women with a preserved uterus are advised to consistently prescribe a gestagen for 10-14 days a month.
Pharmacokinetics
absorption: due to the percutaneous application of Klimara, estradiol is highly absorbed into the systemic circulation;
Distribution: the therapeutic effect of weekly TTS is comparable to continuous low-dose intravenous infusion aimed at the formation of a stable, plateau-like serum estradiol level corresponding to that during the early / middle follicular phase of a woman's reproductive period. Percutaneous administration of the drug avoids significant fluctuations in the serum concentration of estradiol, as well as its metabolites, as occurs in the case of oral estradiol replacement therapy. As a result, the load on the liver is significantly reduced, since a large amount of estradiol and its metabolites are excluded, which, after taking HRT drugs, undergo a presystemic metabolism in the liver (first pass effect). Transdermal administration of estradiol does not affect liver protein synthesis. The weekly application of Klimara provides an even and stable serum estradiol and estrone profile within the desired range. The concentration of estradiol in serum is directly proportional to the area of the patch. The mean equilibrium concentration (Css) of estradiol in the blood is for a patch with an area of 12.5 cm2 ~ 35 pg / ml, for 25cm patch 2 ~ 70 pg / ml. ~ 61% of estradiol is nonspecifically bound to serum albumin, ~ 37% specifically binds to sex hormone binding globulin (SHBG). The apparent volume of distribution (Vd) of estradiol after a single intravenous injection is ~ 1 L / kg. Multiple weekly applications of the patch do not cause accumulation of estradiol and estrone, therefore, their equilibrium serum level corresponds to that observed after a single application;
metabolism: as a result of transdermal application, the biotransformation of estradiol into estrone and conjugates remains within the physiological norm observed in the early follicular phase in women in the reproductive period of life. The ratio of serum levels of estradiol to estrone is about 1, in contrast to the non-physiologically high level of estrone, which is the result of intense metabolism of the hormone due to the first passage through the liver with oral HRT with estradiol, when the observed ratio of estradiol to estrone is less than 0.1. The metabolism of estradiol during transdermal entry into the systemic circulation is similar to that of endogenous hormones and occurs mainly in the liver, as well as extrahepatic, in the kidneys, skeletal muscles, intestines and target organs, with the formation of estrone, estriol,catechol estrogens and their sulfate and glucuronide conjugates, which have distinctly less or even no estrogenic effect;
excretion: The total serum estradiol clearance resulting from a single intravenous injection is in the range of 10-30 ml / min / kg and is highly variable. Partially, estradiol metabolites are excreted in the bile, undergoing the so-called. enterohepatic circulation, but ultimately excreted mainly in the urine in the form of sulfates and glucuronides.
Indications for use
TSS Klimara is recommended for the purpose of HRT for the treatment of symptoms of estrogen deficiency that occurs as a result of natural menopause or after surgical removal of the ovaries.
The drug is also used to prevent postmenopausal osteoporosis in women at high risk of fractures, in case of intolerance or contraindications to the use of other prophylactic drugs prescribed for osteoporosis in the postmenopausal period.
Contraindications
Absolute:
- breast cancer or suspicion of it;
- vaginal bleeding of unexplained genesis;
- hormone-dependent malignant tumors, precancerous conditions or suspicion of them;
- benign / malignant neoplasms of the liver at present or in history;
- deep vein thrombosis in the exacerbation phase, thromboembolic diseases, present or in history;
- the period of pregnancy and lactation (breastfeeding);
- hypersensitivity to any components of the TTS.
When diagnosing the above diseases / conditions against the background of HRT, it is required to interrupt therapy and consult a doctor.
Relative contraindications for the use of Klimara, in which the system should be used with caution, are liver dysfunction, arterial hypertension, uterine myoma, endometriosis, diabetes mellitus.
Klimara, instructions for use: method and dosage
The Klimar transdermal therapeutic system is applied by dermal application.
Application features:
- therapy of symptoms of climacteric syndrome: it is recommended to start treatment with the lowest dose of the patch [area - 12.5 cm 2 (4.5 cm × 3.3 cm) and the rate of release of the active substance 50 μg / day]. If necessary, a higher-dose patch may be used [area - 25 cm 2 (6.3 cm × 4.7 cm) and release rate of the active ingredient 100 μg / day]. Once titration is complete, the lowest effective dosage should be used to relieve symptoms;
- Prevention of osteoporosis: Prevention of postmenopausal bone loss should be initiated immediately after menopause. Long-term treatment is recommended. The dosage regimen is prescribed taking into account the individual characteristics of the patient, the course of therapy can be either continuous or cyclical;
- transition from long-term continuous / cyclic therapy: therapy should be started the next day after the completion of the previous course. The use of estrogens exclusively is practiced in women with hysterectomy. For patients with an intact uterus, progestogen should be added to Klimara's treatment every month for 10-14 days. In the case of using a patch that releases more than 50 μg of the hormone / day, the addition of progestogens did not reveal a protective effect on the endometrium.
The patch should be applied weekly, after removing the used one, but in a different place. For treatment in a cyclic mode, the patch is applied weekly for 3 consecutive weeks, after a 7-day interval without the application of the patch, the next course of treatment begins.
The development of menstrual bleeding normally occurs 2-3 days after stopping the intake of gestagens.
Recommendations for applying the patch:
- The Klimara patch should be attached with the adhesive side (after removing the protective film) on a dry, clean area of the skin.
- The patch must be fixed immediately after opening the package and removing the protective film.
- It is recommended to attach the patch along the spine or on the buttocks. Do not stick the patch on the mammary glands or near them, on the waist area (when wearing tight-fitting clothing, it may come off). It is also necessary to avoid areas of the skin on which it can shift in the patient's sitting position.
- The area chosen for attachment should not be damaged, irritated or greasy.
- To fix the patch, press firmly with the palm of your hand to the application site and hold for about 10 seconds. At the end of the procedure, you need to make sure that the patch is in good contact with the skin, especially around the edges. In case of a loose fit, you need to press on it for better adhesion.
- The place of application should be changed once a week.
- With the patch properly fixed, you can shower and wash in the bathroom as usual. But it can come off the skin in very hot water or when visiting a bath / sauna.
If a woman forgot to change the patch on time, the replacement should be done as soon as possible after the fact of the pass has been established. Then use the next new patch as usual after the end of the 7-day therapy period.
In case of untimely replacement / loss of the patch or its peeling off before the expiration of the 7-day course, you can try to reapply the patch. If this fails, a new patch is used for the remaining days from the 7-day application interval.
Side effects
- local reactions: most often - skin irritation at the site of application;
- central nervous system: headache, dizziness, migraine, depression;
- digestive system: nausea / vomiting, flatulence, epigastric pain, stomach pain, cholestatic jaundice;
- dermatological reactions: melasma, chloasma (may be persistent);
- reproductive system and mammary gland: breakthrough bleeding, smearing vaginal discharge; growth of uterine fibroids; change in the amount of vaginal secretion; soreness and engorgement / enlargement of the mammary glands;
- hypersensitivity reactions: in some cases - itching, allergic contact dermatitis, generalized exanthema;
- other reactions: worsening of porphyria, change in body weight, edema, muscle cramps, change in libido.
Overdose
With the cutaneous application of Klimara, the probability of an overdose is negligible.
Possible symptoms: nausea / vomiting, sometimes withdrawal bleeding.
It is recommended to remove the patch, if necessary, carry out symptomatic therapy.
The specific antidote to estradiol is unknown.
special instructions
Before starting HRT or with re-appointment, a woman is recommended to undergo a thorough general medical and gynecological examination, which should include an examination of the pelvic organs (with a cytological examination of cervical mucus), mammary glands, abdominal cavity, blood pressure control, a study of the blood coagulation system, blood lipid profile. In patients with diabetes mellitus, at least once a year, it is necessary to monitor the blood sugar content.
With the onset of HRT, hormonal contraception should be discontinued, if it is necessary to protect the patient, use non-hormonal contraceptives.
The following conditions and risk factors, observed before starting treatment or progressive, require, in each case, consideration of the potential risk and expected benefit from Klimara therapy before starting / continuing HRT:
- diseases of the cardiovascular system: according to the results of a number of epidemiological studies in patients receiving HRT, there was a slight increase in the incidence of VTE (venous thromboembolism), for example, pulmonary embolism or deep vein thrombosis. When Klimara is prescribed to women with risk factors for VTE, an assessment of the risk / benefit ratio of the therapy is required. Risk factors for VTE include: individual / family history (the presence of VTE in direct relatives at a relatively young age may indicate a genetic predisposition); severe obesity; the age of the patient; prolonged immobilization; serious surgical intervention or extensive trauma (taking into account the etiology of the disease and the duration of immobilization, the issue of temporarily stopping HRT is being considered). Experts did not come to a consensus regarding the possible influence of varicose veins on the development of VTE. Therapy should be stopped immediately if symptoms of thromboembolism are detected or if they are suspected;
- endometrial cancer: Long-term exposure to estrogen increases the risk of endometrial hyperplasia or carcinoma. Studies have confirmed that the additional use of gestagens reduces the likelihood of developing endometrial hyperplasia and cancer of the uterine body;
- breast cancer: according to the results of a meta-analysis of 51 epidemiological studies, it was found that women who received HRT for 5 years had a slightly increased risk of developing diagnosed breast cancer. This can be the result of both an earlier diagnosis of the disease, and the biological effect of HRT, or a combination of both factors. The increase in the relative risk occurs as the duration of therapy increases. This is comparable to the increase in the risk of developing breast cancer, noted in women every year, delaying natural menopause. After discontinuation of HRT / end of treatment, the increased risk gradually disappears during the first 5 years. Diagnosed in women receiving HRT, breast cancer metastasizes less frequently than in those who have not received such treatment;
- liver tumors: after the use of hormonal drugs such as Klimara, in rare cases, benign, and even less often malignant, liver tumors were observed. In extremely rare cases, such tumors can lead to life-threatening intra-abdominal bleeding. The main symptoms of a liver tumor: pain in the epigastric region, an increase in liver size and / or symptoms of hemoperitoneum;
- gallbladder disease: since estrogens increase the lithogenicity of bile, against the background of HRT, some patients have an increased predisposition to gallbladder diseases;
- other conditions: immediate discontinuation of therapy is required in case of newly developing migraine / unusually severe headaches and other symptoms that are possible harbingers of circulatory disorders in the vascular system of the brain and spinal cord.
If, when changing the place of application, according to the recommendations, there is a recurring persistent skin irritation (erythema or itching in the area of the patch), the use of TTS should be discontinued.
The relationship between hormone replacement therapy and clinical arterial hypertension has not been established. Cases of a slight increase in blood pressure in women receiving HRT have been described, but its clinically significant increase with such treatment is extremely rare. At the same time, if clinically significant persistent hypertension develops during HRT in individual cases, the issue of stopping treatment is considered.
With reduced liver function, a significant decrease in the metabolism of sex steroids is possible. Since with the percutaneous intake of the active substance into the body, it does not undergo presystemic biotransformation by the first passage through the liver, HRT is prescribed with caution to patients with impaired hepatic function.
In case of recurrence of cholestatic jaundice / cholestatic pruritus, which developed earlier during pregnancy and with previous use of sex steroids, HRT should be stopped immediately.
In some cases, patients receiving HRT may develop undesirable manifestations of estrogen stimulation, such as abnormal uterine bleeding. With frequent or persistent abnormal uterine bleeding during therapy, endometrial examination is necessary.
Under the influence of estrogens, an increase in the size of uterine fibroids is possible, in which case HRT should be discontinued.
Discontinuation of therapy is also recommended for exacerbation of endometriosis.
If prolactinoma is suspected, the diagnosis should be ruled out before starting treatment.
Chloasma may develop, especially if there is a history of chloasma during pregnancy. With this diagnosis, women receiving TTS therapy need to avoid prolonged sun exposure and exposure to UV radiation.
Conditions that arise or worsen with HRT: migraine, benign diseases of the mammary glands, epilepsy, asthma, porphyria, systemic lupus erythematosus, otosclerosis, chorea minor. Finally, their connection with HRT has not been established, but women using TTS with such diseases should be under close medical supervision.
Drugs for HRT can influence the results of some laboratory tests, including liver function tests; analyzes of the functions of the adrenal glands, kidneys and thyroid gland; determination of the concentration of transport proteins in plasma (corticosteroid-binding globulin and lipid / lipoprotein fraction), parameters of carbohydrate metabolism, indicators of coagulation and fibrinolysis.
Influence on the ability to drive vehicles and complex mechanisms
There were no reports of any negative effect of Klimara on cognitive and psychophysical functions.
Application during pregnancy and lactation
Hormone replacement therapy in pregnant and breastfeeding women is not performed.
According to the results of extensive epidemiological studies, an increased risk of developmental pathologies in children whose mothers received HRT / used hormonal contraceptives before pregnancy and / or teratogenic effects on the fetus, when the drugs were taken inadvertently in the early stages of pregnancy, were not identified.
During lactation, small amounts of sex hormones can be excreted in breast milk.
Pediatric use
Climara is not used in pediatrics.
For violations of liver function
It is contraindicated to use the drug in the presence of a benign / malignant liver tumor at the present time and / or in history.
Drug interactions
Long-term combined use of TTS Klimar with drugs that induce the induction of microsomal liver enzymes, for example, barbiturates, hydantoin derivatives, primidone, rifampicin, carbamazepine, and, possibly, with griseofulvin, topiramate, oxcarbamazepine, felbamate, can contribute to an increase in sex hormones; these drugs can reduce its clinical effectiveness. For 2-3 weeks at the beginning of therapy, the maximum induction of enzymes may not appear, but after the cessation of the course, it may persist for at least 4 weeks.
Drinking large doses of alcohol while undergoing HRT can increase the level of circulating estradiol.
Analogs
Klimara's analogues are Divigel, Estrofem, Estrogel, etc.
Terms and conditions of storage
Store at temperatures up to 30 ° C. Keep out of the reach of children.
The shelf life is 3 years.
After removing the protective film, the patch must be glued immediately. TTS cannot be stored unopened.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Klimar
Women who need to take hormone replacement therapy on an ongoing basis (if only estrogen is needed), the reviews about Klimar are mostly positive. Provided that continuous treatment is required, TTS does not need to be applied every day. The patch is applied once a week and is very convenient when used correctly.
Possible individual intolerance and high cost of the drug are indicated as disadvantages.
Price for Klimara in pharmacies
The approximate price of Klimara (TTS 3.9 mg / 12.5 cm 2) for 4 plasters in a package is 1214–1285 rubles.
Klimara: prices in online pharmacies
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Drug name Price Pharmacy |
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Climara 3.9 mg / 12.5 sq. see transdermal therapy system 4 pcs. RUB 1000 Buy |
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Klimara plaster transderm. 3.9mg / 12.5 sq. Cm 4 pcs. 1095 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
