Nebido 250 mg / ml 4 ml intramuscular injection

The instruction for medical use of Nebido® medicine the Trade name of Nebido® the International unlicensed name Testosterone Dosage Form Solution for intramuscular introduction of 250 mg/ml Structure 1 bottle of drug contains active agent – testosterone undekanoata1000.0 mg excipients: benzyl benzoate, the castor oil purified. The description the Transparent solution which is not supporting strangers of particles. Pharmacotherapeutic group Drugs for treatment of urogenital bodies and sex hormones. Sex hormones and modulators of a reproductive system. Androgens. Derivative 3 oxoandrostenums. Testosterone. The ATX G03BA03 code the Pharmacological Pharmacokinetics Absorption Drug properties represents the intramuscular drug depot containing testosterone undekanoat and for this reason the effect of primary passage is absent. After an intramuscular injection of Solutio oleosa of testosterone undekanoat it is gradually released from depot and it is almost completely split by serumal esterases on testosterone and undekanoyevy acid. Increase of serumal concentration of testosterone of rather initial indicators can be defined already next day after an injection. Equilibrium concentration After the first intramuscular injection of 1000 mg of testosterone of the undekanoat to the men suffering from a hypogonadism, average maximum concentration (Smaks) of testosterone made the 38th nmol/l (11 ng/ml) in 7 days. The second injection was carried out in 6 weeks after the first, and the maximum concentration of testosterone near the 50th nmol/l (15 ng/ml) were reached. The standard interval of introduction to 10 weeks remained during three subsequent introductions, equilibrium concentration were reached between the 3rd and 5th introductions. Averages equilibrium Smaks and Smin made about 37 (11 ng/ml) and the 16th nmol/l (5 ng/ml), respectively. The median of boundaries - and intra-individual variability (coefficient of variation in %) the minimum indicators Smin made 22% (from 9 to 28%) and 34% (from 25 to 48%), respectively. Distribution In blood serum of men about 98% of the circulating testosterone contacts the globulin connecting sex hormones and albumine. Only the free fraction of testosterone is considered biologically active. After intravenous infusion of testosterone to elderly men the seeming volume of distribution was defined at the level of about 1.0 l/kg. Metabolism Testosterone which is formed by splitting of radio communication of testosterone of the undekanoat is metabolized and brought out of an organism to similarly endogenous testosterone. Undekanoyevy acid is metabolized by b-oxidation as well as other aliphatic carboxylic acids. The main active metabolites of testosterone are oestradiol and dihydrotestosterone. Removal Testosterone is exposed to considerable metabolism in a liver and beyond its limits. After administration of radiomechenny testosterone about 90% of radioactivity are noted in urine in the form of glyukuronidny and sulphatic conjugates, and 6% after passing of enterohepatic circulation are found in excrements. The products defined in urine include androsterone and etiocholanolone. After intramuscular administration of drug the speed of release of substance from depot was characterized by elimination half-life of 90±40 days. Testosterone pharmacodynamics undekanoat is ether of a natural androgen, testosterone. The active form – testosterone – is formed as a result of eliminating of a side chain. Testosterone – the most important androgen in a male body mainly synthesized by testicles and, to a lesser extent, bark of adrenal glands. Testosterone is responsible for forming of male sexual characters during pre-natal development, in the early childhood and during puberty, and subsequently – for maintenance of a men's phenotype and androgenozavisimy functions (for example, a spermatogenesis, additional gonads). It also performs functions, in particular, in skin, muscles, kidneys, a liver, marrow and central nervous system. Depending on a target organ, the nature of effect of testosterone is, mainly, androgenic (for example, in a prostate, seed bubbles, appendages of testicles) or proteinaceous and anabolic (in muscles, bones, the haematogenic system, kidneys, a liver). Effect of testosterone in some bodies is shown after peripheral transformation of testosterone into oestradiol which then contacts estrogenic receptors in kernels of target cells (for example, a hypophysis, fatty tissue, a brain, bones and testicular leydigovsky cells). Indications - replacement therapy by testosterone at a hypogonadism at men with clinically and biochemical confirmed deficiency of testosterone the Route of administration and a dosage For an injection of Nebido® enter all contents of 1 bottle containing 1000 mg of testosterone of the undekanoat strictly intramusculary once in 10 – 14 weeks. With such frequency of injections the maintenance of sufficient level of testosterone is provided, and there is no substance cumulation. The initiation of treatment Before an initiation of treatment should be defined the size of content of testosterone in blood serum. Depending on levels of testosterone of serum and clinical symptoms the first interval between injections can be reduced to the minimum, equal 6 weeks, with the subsequent intervals of 10-14 weeks for maintenance therapy. Equilibrium concentration at such load dose can be reached quicker. Individual correction of treatment the Interval between injections has to remain within the recommended range of 10 - 14 weeks. During maintenance therapy it is recommended to carry out regular control of level of testosterone in serum. Determination of levels of testosterone has to be carried out at the end of an interval between injections, taking into account clinical manifestations. Serumal levels have to be in the lower third of range of normal indicators if they are lower than norm, then reduction of an interval between injections is necessary. At high concentrations in serum it is possible to consider a question of expediency of increase in this interval. Special populations of patients Nebido's Children it is not shown for treatment of children and teenagers, clinical assessment at males is younger than 18 years was not carried out (see the section Special Instructions). Patients of advanced age the Available limited data do not assume need of dose adjustment at elderly patients (see the section Special Instructions). Patients with a liver failure Researches at patients with a liver failure were not conducted. Use of Nebido® is contraindicated at men with liver tumors now or in the anamnesis. Patients with a renal failure Researches at patients with a renal failure were not conducted. Operation manuals For intramuscular use. Injections should be carried out very slowly (within two minutes). Небидо® it is intended for strictly intramuscular introduction. It is necessary to watch that Nebido® was entered deeply into a gluteus, when performing general measures of precaution at intramuscular introduction carefully. It is necessary to observe extra care not to allow administration of drug in a vessel (see the section Special Instructions). Contents of a bottle are entered intramusculary right after opening. Side effects With the largest frequency during treatment of Nebido® were observed such side reactions as an acne and pain in the place of an injection. The undesirable medicinal reactions distributed on classes of a system of bodies according to 10.1 versions of MedDRA – the Medical dictionary for regulatory activity are given below. Frequency of side reactions is based on data of clinical trials. Often (from ≥1/100 to & lt, 1/10) - a polycythemia, increase in level of a hematocrit, increase in number of erythrocytes, increase in level of hemoglobin - increase in body weight - inflows of heat - an acne - increase in level of prostatspetsifichesky antigen, pathological changes at inspection of a prostate, a benign hyperplasia of a prostate - various reactions in the place of an injection (pain, discomfort, an itching, an erythema, a hematoma, irritation, other reactions) Infrequently (from ≥1/1000 to & lt, 1/100) - reactions of hypersensitivity - increase in appetite, increase in level of glikozilirovanny hemoglobin, a hypercholesterolemia, a gipertriglitseridemiya - a depression, emotional disturbances, insomnia, concern, aggression, irritability - headaches, migraine, a tremor - cardiovascular disturbances, an arterial hypertension, dizziness - bronchitis, sinusitis, cough, short wind, snore, a dysphonia - diarrhea, nausea - pathological indicators of function of a liver, increase in level of aspartate aminotransferase - an alopecia, an erythema, rash (including papular), an itching, xeroderma - joint pains, extremity pains, musculoskeletal constraint, increase in level of a kreatinfosfokinaza in blood - reduction of a stream of urine, an ischuria, disturbances from an urinary system, a nocturia, a dysuria - an intraepithelial new growth of a prostate, consolidation of a prostate, prostatitis, disturbances from a prostate, changes of a libido, pain in testicles, consolidation of mammary glands, mammary gland pain, a gynecomastia, increase in level of oestradiol, increase in level of testosterone - fatigue, an asthenia, a hyperhidrosis, night perspiration. Seldom (from ≥ 1/10000 to & lt, 1/1000) the Pulmonary fat microembolism (frequency is based on quantity of injections). The Pulmonary microembolism at use of Solutio oleosa in rare instances can result the description of some side effects in such signs and symptoms as cough, short wind, an indisposition, a hyperhidrosis, pains behind a breast, dizziness, paresthesias, a faint. These reactions can appear in time or right after an injection and are reversible. Cases when suspicion of a pulmonary microembolism took place, were noted seldom in clinical trials (≥ 1/10000 and & lt, 1/1000), and according to post-registration experience (See the section Special Instructions). In addition to above-mentioned side reactions the following reactions were noted at treatment by testosterone drugs: nervousness, hostility, a short-term involuntary apnoea during sleep (an apnoea in a dream), various skin reactions, including dandruff and seborrhea, the increased growth of hair, the increased frequency of erections and seldom or never jaundice. Therapy by testosterone drugs in high doses usually causes the termination or decrease in a spermatogenesis which returns to norm after the treatment termination. Replacement therapy by testosterone at a hypogonadism in rare instances can cause persistent painful erections (priapism). At long-term treatment by testosterone or at its use in high doses the increase of cases of a delay of liquid and hypostases are possible. Contraindications - androgenozavisimy cancer of a prostatic or mammary gland at men - liver tumors or in the anamnesis - hypersensitivity to active ingredient or to any of Nebido® excipients is contraindicated now for use for women. Medicinal interactions Oral anticoagulants Testosterone and its derivatives can increase activity of oral anticoagulants. Carrying out careful control, especially at the beginning or at the end of therapy by an androgen is required from the patients accepting oral anticoagulants. Carrying out the strengthened control of a prothrombin time and definition of the international normalized relation (INR) is recommended. Other interactions Simultaneous use of testosterone and adrenocorticotropic hormone (AKTG) or corticosteroids can strengthen formation of hypostases, therefore, these substances should be applied with care, especially at patients with diseases of heart or liver and also at the patients inclined to hypostases. Influence on results of laboratory researches: Androgens can reduce level thyroxine - the connecting globulin that leads to decrease in level of the general T4 in serum and to strengthening of capture of T3 and T4 ionic pitch. However true levels of free thyroid hormone remain invariable, clinical signs of dysfunction of a thyroid gland are absent. The special instructions Nebido® should be applied only at manifestations of a hypogonadism (hyper - and hypogonadotropic) and only in case prior to treatment all other causes which could cause these symptoms were excluded. Insufficiency of testosterone has to be shown clinically (regression of secondary sexual characteristics, change of the structure of a body, an asthenia, decrease in a libido, erectile dysfunction, etc.) and has to be confirmed with two separate measurements of level of testosterone in blood. Medical examination before therapy by testosterone all patients have to undergo careful inspection to exclude a prostate cancer. Careful and regular control prostatic and mammary glands has to be carried out, at least, once a year, according to the recommended methods (a manual rectal research, assessment of the DOG levels in serum) at the patients receiving therapy by testosterone and two times a year at patients of advanced age and patients of risk group (with clinical or family factors). It is necessary to consider local recommendations about control of safety at replacement therapy by testosterone. Laboratory researches during treatment the level of testosterone follows it is necessary to control in comparison to initial level at regular intervals. The dose needs to be selected individually to provide the serumal level of testosterone corresponding to level at an eugonadizm. At patients on long therapy the following laboratory parameters have to be defined by androgens also periodically: hemoglobin, hematocrit, functional trials of a liver and lipidic profile. In view of variability of laboratory results all determination of level of testosterone has to be carried out in the same laboratory. Tumors Androgens can accelerate progressing of a subclinical prostate cancer and benign hyperplasia of a prostate. Небидо® it is necessary to apply with care at oncological patients with risk of emergence of a hypercalcemia (and the related hypercalcuria) owing to metastasis in a bone. At these patients carrying out regular control of concentration of calcium in serum is recommended. It was reported about cases of development of benign and malignant tumors of a liver in patients against the background of reception of hormonal means, including androgenic drugs. In case of emergence at the men receiving treatment of Nebido®, complaints to severe pain in upper area of a stomach, increase in a liver or symptoms of intra belly bleeding at differential diagnostics it is necessary to consider a liver tumor. A heart, liver and renal failure It is necessary to observe precautionary measures at patients with a heavy heart, liver or renal failure, or coronary heart disease as therapy by testosterone can cause the heavy complications which are characterized by hypostases with existence or absence of stagnant heart failure. In similar cases it is necessary to stop treatment immediately. A liver and renal failure of the Research of efficiency and safety of this drug at patients with a renal or liver failure were not carried out. In this regard it is necessary to be careful when performing replacement therapy by testosterone at such patients. Heart failure It is necessary to observe precautionary measures at the patients predisposed to hypostases, for example, with a heavy heart, liver or renal failure, or coronary heart disease as treatment using androgens can lead to strengthening of a delay of sodium and water. In case of the heavy complications which are characterized by hypostasis with/without stagnant heart failure it is necessary to stop immediately treatment by testosterone (see the section Side effects). Небидо® it is necessary to apply with care at the patients having arterial hypertension as testosterone can increase arterial blood pressure. Fibrillation disturbance As a rule, it is always necessary to observe restrictions on use of intramuscular injections for patients with the acquired or inherited disorders of fibrillation. It was reported about cases of increase in activity of coumarinic oral anticoagulants at use of testosterone and its derivatives (see
the section Medicinal Vzaimodeyst Iya). Testosterone should be applied with care at patients with a thrombophilia as in post-registration researches and reports it was reported about cases of development of thrombosis at them during therapy by testosterone. Other conditions of Nebido® should be applied with care at patients with epilepsy and migraine as there can occur exacerbation of these diseases. At which at patients as a result of replacement therapy the androgens reached normal concentration of testosterone in plasma, increase in sensitivity to insulin can be observed. Some clinical signs, such as irritability, nervousness, increase in body weight, long or frequent erections, can indicate surplus of androgens that demands dose adjustment. The available sleep apnoea syndrome can amplify. The athletes receiving replacement therapy by testosterone at primary or secondary men's hypogonadism should be infromirovat that this medicine contains active ingredient which can give positive reaction when conducting anti-doping tests. Androgens are not used for strengthening of development of muscles in healthy faces, as well as for increase in physical abilities. Небидо® it is necessary to cancel completely in cases when symptoms of excessive influence of androgens proceed or repeatedly arise against the background of use of drug in the recommended mode. Introduction As well as all Solutio oleosa, Nebido® should be entered strictly intramusculary and very slowly (within two minutes). The pulmonary microembolism against the background of use of Solutio oleosa in rare instances can result in such signs and symptoms as cough, short wind, an indisposition, dizziness, a faint, a hyperhidrosis, paresthesias, stethalgias. These reactions can appear in time or right after an injection and are reversible. In this regard, it is necessary to perform inspection in time or right after an injection for the purpose of early identification of signs and symptoms of a pulmonary fat microembolism. As a rule, in these cases carry out the supporting treatment, for example, prescribing of oxygen. It was reported about suspicion on anaphylactic reactions after use of Nebido®. Use in pediatrics of Nebido® it is not shown for treatment of children and teenagers 18 years are younger. Use for older persons Experience of use of Nebido® for patients of advanced age is more senior than 65 years is limited. At the moment there is no consensus concerning normal limits of level of testosterone depending on age. However it is necessary to take into account that with age there is a physiological decrease in level of testosterone in blood serum. Patients with a liver failure Researches at patients with a liver failure were not conducted. Use of Nebido® is contraindicated at men with liver tumors in the anamnesis or now. Patients with a renal failure Researches at patients with a renal failure were not conducted. Pregnancy and lactation of Nebido® it is not shown for use for women, and it should not be applied at pregnant women or the feeding women (see the section Contraindications). Fertility Replacement therapy by testosterone can cause reversible decrease in a spermatogenesis. Features of influence of medicine on ability to run motor transport and potentially dangerous mechanisms. Use of drug does not affect ability to run motor transport and potentially dangerous mechanisms. The overdose in case of overdose of special therapeutic measures is not required, except for the temporary termination of therapy or a dose decline. A form of release and packing On 4 ml of drug in the bottle from brown glass of I type the volume of 6 ml corked by a brombutilovy stopper of gray color and a running in aluminum with a lid from polypropylene. On 1 bottle together with the instruction for medical use in the state and Russian languages place in a cardboard pack. To Store storage conditions at a temperature not above 25 °C. To store out of children's reach! A period of storage of 5 years of the Condition of release from drugstores According to the prescription of Proizvoditel Bayer AG, Berlin, Germany the Owner of the registration certificate of Bayer AG, Leverkusen, Germany the Address of the organization in the territory of the Republic of Kazakhstan, the accepting claim (offer) on quality of medicines from consumers: TOO Bayer KAZ Timiryazev St., 42, pavilion 15, office 301 050057 of Almaty, Republic of Kazakhstan, ph. +7 727 258 80 40, fax: +7 727 258 80 39, e-mail: kz.claims@bayer.com the Address of the organization in the territory of the Republic of Kazakhstan responsible for post-registration observation of safety of medicine TOO Bayer KAZ Timiryazev St., 42, pavilion 15, office 301 050057, Almaty, the Republic of Kazakhstan ph. +7 701 715 78 46 (round the clock) ph. +7 727 258 80 40, vn. 106 (in working hours) fax: +7 727 2588 039
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