Oestramonum 50

General characteristics. Structure:

Active ingredient: oestradiol;

1 plaster of 20 cm in size 2 with an average speed of release of oestradiol of 50 mkg a day contains oestradiol 4 mg;

excipients: da-tocopherol concentrate, copolymer acrylate, Pegoterat lining.

Pharmacological properties:

Pharmacodynamics. The transdermal system contains oestradiol, chemically and biologically identical to that which is synthesized in a human body. Effect of oestradiol at the level of receptors is considerable stronger, than action of its metabolites (estrone and estriol). After a menopause the majority of endogenous estrogen are produced by transformation of androstendion which cosecretes bark of adrenal glands, in estrone in peripheral fabrics. Therefore estrone and its sulphatic conjugated form are the prevailing estrogen in a blood-groove of women during the post-menopausal period. 

The reduction of products of estrogen ovaries noted after a menopause or an oophorectomy leads to acceleration of loss and a resorption of a bone tissue. The resorption of a bone tissue occurs quicker, than its formation, especially in the first years after a menopause when note the biggest loss of bone weight. At some women such changes lead to reduction of bone weight, osteoporosis and increase in risk of changes. Fractures of vertebras — the most widespread type of the changes associated with osteoporosis at women during the post-menopausal period. Women in the period of a postmenopause at whom concentration of oestradiol in a blood plasma is not exposed to definition (<5 pg/ml) and with the high level of the globulins connecting sexual steroids treat group of the increased risk of fractures of femurs and vertebrae. Post-menopausal therapy by estrogen quickly normalizes a resorption and formation of a bone tissue that leads to recovery of bone balance. Protection is effective during all treatment.

Pharmacokinetics. Use of oestradiol in the form of a transdermal system provides long and uniform receipt it in an organism. Concentration of oestradiol in a blood plasma can be controlled, preventing overdose. After a plaster attachment Oestramonum 50, oestradiol is well soaked up through the unimpaired skin which provides its resistant level in a blood-groove during treatment. The calculated average daily speed of release of oestradiol makes 50 mkg/days. Unlike dosage forms for oral administration, transdermalny use of oestradiol allows to prevent his intesivny metabolism during the first passing through a liver. At constant use of a plaster Oestramonum 50, average concentration of oestradiol in a blood plasma makes about 34 mg/ml, Cmax — about 48 mg/ml. After removal of a plaster the amount of oestradiol decreases to initial level for 12–24 h. 

Oestradiol is metabolized in a liver with formation of estrone and its conjugates. The ratio of concentration oestradiol/estrone in a blood plasma at use of a plaster fluctuates within 0,2–0,5:1 that corresponds to physiological level. Oestradiol partially contacts proteins of a blood plasma.

Oestradiol and its metabolites are generally removed with urine in the form of glucuronides or sulfates, and also partially — with bile. Т½ — about 2-3 h. 

At reusable use of accumulation of oestradiol and estrone in a blood plasma it is not revealed.

Indications to use:

Replacement hormonal therapy at pre-and post-menopausal deficit of estrogen at women. Prevention of post-menopausal osteoporosis at women at whom there passed no more than 5 years after approach of a menopause.

Route of administration and doses:

Treatment needs to be begun with a minimal effective dose.

It is recommended to apply 1 plaster at an interval of 3–4 days (on average 2 times a week). If after 3 months of use of a plaster symptoms of deficit of estrogen are not eliminated, the dose can be raised, but the maximum dose should not exceed 100 mkg/days.

It is possible to apply a plaster Oestramonum 50 at any time, but patients who leave cyclic therapy should begin drug use next day after the termination of the previous scheme of treatment.

At women a plaster apply to prevention of post-menopausal osteoporosis in a dose 50 mkg/days (1 plaster at an interval of 3–4 days). 

Experience of use of a plaster Oestramonum 50 at women is aged more senior than 65 years is limited.

Route of administration: 

1. Just before use it is necessary to tear off a protective cover of a bag, having cut it is closer to edge and to get a plaster, without damaging it.

2. The plaster should be bent carefully along perforation up and from top to bottom until the most part of a protective film separates along a perforated strip from a sticky surface of a transdermalny plaster. This part of a protective film is removed for one of the received tips.

3. The open sticky surface of a plaster is imposed on the healthy cleared skin of an outside surface of a hip.

4. Then a convex part of a transdermalny plaster is slightly lifted so that it would be possible to remove the rest of a protective film, and fixed completely.

5. After full fixing of a plaster it needs to be pressed a hand throughout 10 pages.

The plaster cannot be applied in the site of mammary glands. When using each new plaster it is necessary to change the place of application. Just before application the site of skin should be degreased, skin should not be damaged or with irritations. It is not necessary to fix a plaster on such sites from which when sitting it can move. After fixing of a plaster it is necessary to be convinced that it well was fixed, especially at edges. If the plaster does not keep, it should be pressed stronger for strengthening.

If the plaster is attached correctly, the patient can take a bath or a shower, as usual. However it can come unstuck from skin at contact with very hot water or in a sauna. It is necessary to protect a plaster from hit of direct sunshine.

If the plaster came unstuck partially or completely before the fixed time (earlier than in 3–4 days), it is necessary to paste a new plaster. If the next use of a plaster was missed, the new plaster should be pasted as soon as possible. 

Treatment duration 

Duration and schemes of treatment are defined by the doctor individually. The plaster is applied in the form of mono - or during a combination therapy. 

At cyclic use in 3 weeks of treatment it is necessary to make 1 week of a break.

To women after a hysterectomy or if symptoms of deficit of estrogen intensively recur throughout a break in treatment, it is possible to appoint continuous, acyclic treatment.

Therapy by estrogen should be supplemented with regular use of gestagen. Gestagena it is necessary to apply for the last 12–14 days of each 28-day course of therapy by oestradiol.

Features of use:

Replacement hormonal therapy should be begun only for treatment of such post-menopausal symptoms which negatively influence quality of life. Not less than 1 time a year it is necessary to carry out careful assessment of a ratio of advantage and risk of therapy before the beginning or continuation of use of a plaster Oestramonum 50.

Reactions in the place of use. At topical administration of a plaster manifestation of heavy anaphylactic reactions and a Quincke's disease is very seldom possible. Reactions from skin (urticaria, an itch, hypostasis of lips, language, a throat, person, extremities) are possible, respiratory tracts (the complicated breath) or a GIT (an abdominal pain, vomiting). At emergence of an angioedema use of a plaster should be stopped. 

Estrogen is capable to strengthen and aggravate symptoms of a Quincke's disease, in particular at women with hereditary tendency to it.

At existence or an aggravation of any of the diseases or risk factors provided below special control of the state of health of the patient is recommended.

Venous thromboembolism. Results of researches using standard doses of estrogen at monotherapy or in a combination with progestogens give the grounds to make the assumption concerning increase in risk of development of a venous thromboembolism, that is a deep vein thrombosis or an embolism of a pulmonary artery. Thereof it is necessary to weigh carefully a ratio risk/advantage of treatment.

Treat the conventional risk factors of development of a venous thromboembolism: the personal anamnesis, the family anamnesis (the case of a venous thromboembolism at close relatives at rather early age can testify to genetic tendency) and obesity of heavy degree. The risk of developing of a venous thrombembolia also increases with age. The question of a role of a varicosity in development of a venous thromboembolism remains contradictory.

The risk of developing of a venous thrombembolia can temporarily increase at a long immobilization, after serious planned or posttraumatic operation or a severe injury. The issue of temporary phase-out of a plaster Oestramonum 50 should be resolved depending on character of circumstances and duration of an immobilization.

Arterial thromboembolism. Results of clinical trials using a combination of the conjugated estrogen and a medroksiprogesteron of acetate (MPA) in the continuous mode indicate possible increase in risk of development of a coronary disease of heart for the 1st year of their use. At continuation of treatment did not note any advantages of rather cardiovascular system. Results of researches showed potential decrease in frequency of a coronary disease of heart at women at the age of 50–59 years at which applied monotherapy by estrogen, in the absence of the general advantages in population. Other negative effect is increase in risk of developing of a stroke for 30–40% at monotherapy by estrogen or their use in a combination with MPA. However dependence on a route of administration is not established. 

Endometrial cancer. Long monotherapy by standard doses of estrogen increases risk of development of a hyperplasia or endometrial cancer. At use of a plaster Oestramonum 50 considerable stimulation of an endometria thanks to a low dose of oestradiol in drug was not revealed. However clinical control of the state of health of the women receiving therapy by estrogen during the post-menopausal period is necessary (for example determination of thickness of an endometria by means of transvaginal ultrasonography once a year). In the presence of not diagnosed persistent or recurrent pathological vaginal bleeding for the purpose of an exception of a malignant state it is necessary to apply adequate diagnostic measures, including an endometria biopsy for indications.

Breast cancer. Increase in risk of development of a breast cancer in the women applying standard doses of estrogen in monotherapy or in a combination with progestogens for many years is established. These facts can be connected with earlier diagnosis, a promoting effect on the existing tumors or association of both factors. 

The relative risk increases with a duration of treatment and can be minimum or invariable at monotherapy estrogen. 

Increase in risk of detection of a breast cancer is noted, for example, with a delay of the beginning of a natural menopause, the use of alcoholic beverages or obesity.

In several years after replacement hormonal therapy increase in risk is leveled.

It was noted that the tumors revealed at women to whom carry out or carried out recently replacement hormonal therapy, the tumors revealed at the women who were not receiving replacement hormonal therapy are characterized by the highest extent of differentiation, than. The spread of the revealed tumor given relatively for borders of a mammary gland is unconvincing.

Replacement hormonal therapy increases density of pictures at mammography researches that can negatively influence diagnosis of a breast cancer in certain cases. 

Influence of a low dose of estrogen which contains in a plaster Oestramonum 50 in connection with risk of development of a breast cancer it is not investigated.

Ovary cancer. The increased risk of development of cancer of ovary in the women receiving replacement therapy by estrogen throughout the long period (> 10 years) is defined whereas the metaanalysis of researches did not show the increased risk for the women receiving replacement therapy by estrogen. Taking into account the above, influence of replacement therapy on development of cancer of ovary is not established.

Influence of a low dose of estrogen which contains in a plaster Oestramonum 50 on risk of development of cancer of ovary is not investigated yet.

Liver tumor. After use of hormonal drugs, including estrogen, in some cases revealed development high-quality, and is even more rare — malignant tumors of a liver. In some cases these tumors were the reason of intra belly bleeding which threatened life. At pain in an upper part of a stomach, increase in a liver or symptoms of intra belly bleeding at differential diagnosis it is necessary to consider probability of existence of a tumor of a liver.

Cholelithiasis. It is known that estrogen raises a bile litogennost. Some women are inclined to diseases of a gall bladder during treatment of estrogen.

Dementia. It is not proved that reception of hormones can increase risk of development of dementia if treatment is begun at women at the age of ≥65. The risk can be reduced if to begin treatment during the early menopausal period. It is not established whether these facts of other drugs of replacement hormonal therapy concern. 

Other states 

Reasons for the immediate termination of therapy: therapy should be stopped immediately in case of identification of any of contraindications, and also at emergence of the states and diseases provided below:

the migrenepodobny, frequent and unusually severe headache which developed for the first time, or other symptoms which, perhaps, are antecedent signs of occlusion of vessels of a brain;

recurrence of cholestatic jaundice or cholestatic itch which was celebrated for the first time during pregnancy or the previous use of sexual steroids;

symptoms of trombotichesky disturbances or suspicion on their emergence.

At suspicion on existence of a prolaktinoma before an initiation of treatment it is necessary to exclude probability of such disease.

The leiomyoma and fibroma of a uterus can increase in sizes under the influence of estrogen. In that case therapy should be stopped.

It is recommended to stop treatment if during therapy the endometriosis recurrence is celebrated.

In the place of use of a plaster can reveal persistent irritation of skin (for example a perstistiruyushchy erythema or an itch).

To the general communication between use of replacement hormonal therapy and development of clinical AG it is not established. It was reported about slight increase of the ABP at women who accept standard doses of estrogen at monotherapy or in a combination with progestogens, clinically significant cases of increase in the ABP noted seldom.

Sex hormones can badly be metabolized at patients with abnormal liver functions. Though at transdermalny use of hormones the effect of the first passing through a liver is not revealed, such patients need to apply estrogen with care.

The available information does not confirm increase in risk of a diabetes mellitus at oestradiol use. Transdermalny use of estrogen can be an optimum form of use for women with a diabetes mellitus of the II type (insulin-dependent). It is necessary to appoint Oestramonum 50 sick diabetes mellitus of the II type and with accessory factors of risk (such as smoking, blood coagulation disturbance) with care; patients have to be inspected regularly during its use.

In certain cases can note a hloazma, especially at women with hloazmy pregnant women in the anamnesis. At use of a plaster Oestramonum 50 women predisposed to emergence of a hloazma should avoid stay in the sun or ultra-violet radiation.

It is established that at use of standard doses of estrogen at monotherapy or in a combination with progestogens the listed below states and diseases can arise or become aggravated. Though there is no confidence that these changes are connected with therapy, it is necessary to observe attentively patients at whom epilepsy, benign diseases of mammary glands, asthma, migraine, a porphyria, an otosclerosis, a system lupus erythematosus, a hysterical chorea are revealed.

Medical inspection / consultation 

Before the beginning or resuming of use of the drug Oestramonum 50 it is necessary to study carefully the anamnesis of the patient and to conduct physical examination, in view of contraindications (see CONTRAINDICATIONS) and cautions (see FEATURES of USE) and to periodically repeat similar inspections. Frequency and the nature of inspections have to be based on the existing norms of medical practice taking into account specific features of each patient. Pelvic bodies, including standard cytologic inspection of a neck of uterus, abdominal cavity, mammary glands, measurement of the ABP are surveyed, as a rule.

Use during pregnancy and feeding by a breast. To use drug during pregnancy and feeding by a breast contraindicated.

Children. Drug is not appointed to children.

Ability to influence speed of response at control of vehicles or work with other mechanisms. It is unknown.

Side effects:

Undesirable effects are classified by the frequency of manifestations: very often (≥1/10), it is frequent (≥1/100, <1/10), sometimes (≥1/1000, <1/100), is rare (≥1/10 000, <1/1000), is very rare (<1/10 000), unknown (frequency cannot be estimated due to the lack of data).

Reactions in the place of use (such as erythema and itch), a headache, feeling of tension in mammary glands and a stethalgia, and also painful feelings during periods and the complaint during a menstrual cycle — the most widespread by-effects at drug use.

Disturbance from immune system: very seldom — a small tortoiseshell, anaphylactoid reactions, hypersensitivity (including anaphylactic reactions and angioedy).

Disturbance of metabolism and food: sometimes — a hypercholesterolemia, increase in body weight; very seldom — change of tolerance to carbohydrates.

Mental disturbances: often — a depression; sometimes — uneasiness; very seldom — an exacerbation of epilepsy.

Disturbance from TsNS: very often — a headache; often — nervousness, drowsiness, sleeplessness, changes of mood, irritability, inflows; sometimes — migraine, dizziness; seldom — paresthesias; very seldom — a chorea.

Disturbances from an organ of sight: sometimes — a vision disorder, feeling of dryness in eyes; very seldom — intolerance of contact lenses.

Disturbances from cardiovascular system: sometimes — AG, tachycardia, a loss of consciousness; seldom — a venous thromboembolism, heavy feeling in legs.

Disturbances from a GIT and gepatobiliarny system: often — nausea, dyspepsia, a meteorism, diarrhea, an abdominal pain, increase in appetite; sometimes — vomiting, a lock, increase in level of enzymes in a liver; seldom — change of hepatic functions and disturbance of outflow of bile (formation of stones in a gall bladder).

Disturbances from skin and hypodermic cellulose: very often — reactions in the place of use, including irritation of skin, an erythema; often — an acne, skin rash, a xeroderma, an itch; sometimes — skin discoloration; seldom — an alopecia; very seldom — a skin necrosis, emergence of excess hair, a multiformny erythema, a knotty erythema and hemorrhagic rash, a hloazma or a melanosis.

Disturbances from a musculoskeletal system and connecting fabric: sometimes — an arthralgia, spasms of muscles; seldom — a myasthenia.

Respiratory disturbances: sometimes — a pharyngalgia.

Disturbances from an urinary system: sometimes — a dysuria, infectious diseases of an urinary system.

Disturbances from reproductive system and mammary glands: very often — feeling of tension and mammary gland pain; sometimes — increase in mammary glands, uterus spasms, an endometria hyperplasia, vaginal allocations, strengthening of secretion from a neck of uterus, new growths of a neck of uterus, uterus pathology, uterine/vaginal bleedings, including a krovomazaniye, pain in the field of a basin, endometria pathology, a vulvovaginitis, vaginal candidiasis, dryness of a vagina, a breast cancer, an oothecoma, fibrocystic diseases of mammary glands, a cyst in mammary glands, an aberration of indicators of a cytologic smear, a falling of the womb; seldom — a uterus leiomyoma, formation of cysts out of pipes, endocervical polyps, a galactorrhoea.

 

General disturbances: often — pain, a dorsalgiya, an adynamy, peripheral hypostases, change of body weight; sometimes — an indisposition; seldom — change of a libido, allergic reactions.

Interaction with other medicines:

Level of metabolic transformation of estrogen can increase at simultaneous use of means which activate enzymes of system of P450 cytochrome. Phenobarbital, Phenytoinum, carbamazepine and antibacterial drugs belong to such active agents (such as rifampicin, рифабутин, not Virapinum and эфавиренз).

Though ритонавир and нелфинавир treat strong inhibitors, they gain properties of activators of enzymes at simultaneous use with steroid hormones.

The herbal remedies containing a St. John's Wort made a hole (Hypericum perforatum) also raise indicators of metabolic transformation of estrogen.

The increased metabolism can lead to decrease in efficiency of hormone and changes of characteristics of uterine bleeding. 

At transdermalny use of oestradiol the effect of the first passing through a liver is eliminated therefore hormone level in an organism in the presence of activators of enzymes changes less significantly, than at oral administration.

CYP 3A4 inhibitors, such as erythromycin, кларитромицин, кетоконазол, итраконазол, ритонавир and grapefruit juice, can increase concentration of estrogen in a blood plasma that can promote manifestation of side effect.

Estrogen strengthens therapeutic influence and by-effects at use of Imipraminum. 

At simultaneous use with cyclosporine increase in concentration of cyclosporine, creatinine and transaminases in a blood plasma is possible. 

Estrogen can influence portability of glucose and the therapeutic answer to insulin therefore dose adjustment of anti-diabetic drugs or insulin is necessary.

Estrogen can reduce effect of anti-hypertensive drugs and anticoagulants.

Excessive alcohol intake during use of replacement hormonal therapy can lead to increase in level of oestradiol in a blood-groove.

 

Reception of sexual steroids can influence results of laboratory researches, including biochemical parameters of function of a liver, thyroid gland, epinephral glands and kidneys, level of transport proteins, such as globulin which connects corticosteroids and fractions of lipids/lipoproteins, parameters of carbohydrate metabolism, and also parameters of coagulation and a fibrinolysis.

Contraindications:

 

Hypersensitivity to oestradiol or other components of drug. The diagnosed or estimated breast cancer; the diagnosed or estimated estrogenzavisimy malignant tumor (especially an endometria carcinoma); vulval bleeding of unspecified genesis; not treated hyperplasia of an endometria; existence in the anamnesis of idiopathic jaundice or thromboembolic diseases of veins (especially deep vein thrombosis, pulmonary embolism); active or thromboembolic diseases of arteries (especially stenocardia, myocardial infarction); a serious illness of a liver (syndromes the Cudgel — Johnson, the Rotor); porphyria; liver tumors during this period or in the anamnesis (high-quality or malignant).

Overdose:

At such route of administration the overdose of oestradiol is improbable. There can be nausea, vomiting, and also in certain cases — cancellation bleeding.

There is no specific antidote. The plaster should be removed. Symptomatic treatment.

Storage conditions:

At a temperature up to 25 °C.

Issue conditions:

According to the recipe

Packaging:

Plaster of transdermas. 50 mkg/days bag, No. 6