Tevanat 70 mg tab No. 4 buy in a pharmacy in Izhevsk and Udmurtia

Tevanat 70 mg tab No. 4

Dosage

70 mg

Active substance

Alendronic acid

Manufacturer

Teva Pharmaceutical Enterprises Ltd (Israel)

Shelf life

3 years

Storage conditions

At a temperature not exceeding 30 °C

Registration certificate number

LS-002267 dated 07/12/2018

Compound

Pills	1 table
active substance:
alendronate sodium monohydrate	81.2 mg
(corresponds to 70 mg alendronic acid)
excipients: MCC - 113.8; croscarmellose sodium - 3 mg; magnesium stearate – 2 mg

Characteristic

Pills	1 table
active substance:
alendronate sodium monohydrate	81.2 mg
(corresponds to 70 mg alendronic acid)
excipients: MCC - 113.8; croscarmellose sodium - 3 mg; magnesium stearate – 2 mg

Description of the dosage form

White or off-white, flat, round tablets with a bevel and an engraving “T” on one side.

Pharmacokinetics

Suction.

When taken orally on an empty stomach in a dose range from 5 to 70 mg immediately 2 hours before breakfast, the bioavailability of alendronic acid in women is 0.64%, in men - 0.6%. The bioavailability of alendronic acid is reduced by 40% when taken on an empty stomach 1–1.5 hours before breakfast. After drinking coffee and orange juice, bioavailability is reduced by approximately 60%. The concentration of alendronic acid in the blood plasma after oral administration at a therapeutic dose is below the possible limit of detection (less than 5 ng/ml).

Distribution.

The binding of alendronic acid to plasma proteins is about 78%. Alendronic acid is distributed into soft tissues, and then quickly redistributed to the bones, where it is fixed, or is excreted through the kidneys.

Metabolism.

Does not undergo biotransformation.

Excretion.

Output unchanged. The elimination process is characterized by a rapid decrease in the concentration of alendronic acid in the blood plasma and an extremely slow release from the bones.

Pharmacodynamics

Alendronic acid acts as a specific inhibitor of osteoclast-mediated bone resorption, reduces the activity of osteoclasts, and inhibits bone resorption. Restores a positive balance between bone resorption and restoration. Increases the mineral density of the bones of the spine and other skeletal bones, promotes the formation of bone tissue with a normal histological structure.

Contraindications

hypersensitivity to alendronic acid and other components of the drug;

hypocalcemia;

conditions leading to slower movement of food through the esophagus (including strictures or achalasia of the esophagus);

the patient's inability to stand or sit upright for at least 30 minutes;

severe renal failure (Cl creatinine <35 ml/min);

severe disturbances of mineral metabolism;

childhood;

pregnancy;

breastfeeding period.

Carefully:

Gastrointestinal diseases in the acute phase (including dysphagia, gastroesophageal reflux disease, Barrett's esophagus, gastritis, duodenitis, gastric and duodenal ulcers), hypovitaminosis D.

Use during pregnancy and breastfeeding

Due to insufficient data on the use of alendronic acid, Tevanat® is contraindicated during pregnancy and breastfeeding.

Directions for use and doses

Inside

To ensure normal absorption of the drug and reduce the risk of adverse reactions, the recommendations for use and dosage should be strictly followed.

Recommended dose - 1 tablet. (70 mg) 1 time per week, with a glass of water at least 30 minutes before the first meal, drinks or other drugs. Take the drug with plain water only, since other drinks (including mineral water), foods and some medications may reduce the bioavailability of Tevanat®. The tablets must not be chewed or dissolved.

After taking the drug, the patient must maintain an upright body position (standing or sitting) for at least 30 minutes. Do not take the drug before bed or before getting out of bed in the morning.

Elderly patients.

No dose adjustment is required.

Kidney failure.

When creatinine Cl >35 ml/min, no dose adjustment is required.

Side effects

The incidence of side effects is classified according to WHO recommendations: very often (at least 10%); often (at least 1%, but less than 10%); infrequently (at least 0.1%, but less than 1%); rare (not less than 0.01%, but less than 0.1%); very rare (less than 0.01%).

From the gastrointestinal tract:

often - abdominal pain, dyspepsia, sour belching, diarrhea, constipation, dysphagia, flatulence, gastritis, gastric ulcer, ulceration of the esophageal mucosa; uncommon - nausea, vomiting, gastritis, esophagitis, erosion of the esophageal mucosa, gastric ulcer (including complicated by bleeding (melena); rarely - esophageal stricture, ulceration of the oropharyngeal mucosa, perforation of the esophagus, bleeding from the upper gastrointestinal tract (connection with alendronic acid has not been established).

From the musculoskeletal system:

often - pain in bones, muscles, joints, cramps; rarely - osteonecrosis of the jaw (mainly in cancer patients taking bisphosphonates, but similar cases have also been observed in patients undergoing therapy for osteoporosis); unknown frequency - stress fracture of the proximal femur, associated or not associated with trauma.

From the side of metabolism:

rarely - symptomatic hypocalcemia, usually associated with predisposing conditions, hypophosphatemia.

From the side of the central nervous system:

often - headache, dizziness, disturbance of taste.

From the senses:

rarely - uveitis, scleritis, episcleritis.

Allergic reactions:

uncommon - rash, itching, erythema; rarely - rash associated with photosensitivity, urticaria, angioedema; very rarely - severe skin reactions, including erythema multiforme exudative (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome).

Other:

rarely - transient symptoms similar to those in the acute phase of the disease (myalgia, malaise and rarely fever), usually at the beginning of treatment.

Interaction

When taken concomitantly with food, drinks containing calcium (including mineral water), nutritional supplements, antacids and other oral medications, the absorption of alendronic acid may be impaired. In this regard, the interval between taking alendronic acid and other oral medications should be at least 30 minutes.

The combined use of alendronic acid (but not simultaneous use) with estrogen preparations is not accompanied by a change in their action or the development of side effects.

Oral administration of prednisolone is not accompanied by clinically significant changes in the bioavailability of alendronic acid.

NSAIDs increase the side effects of alendronic acid on the gastrointestinal tract.

Overdose

Symptoms:

hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis or erosive and ulcerative lesions of the gastrointestinal mucosa are possible.

Treatment:

taking milk or a calcium-containing antacid to bind alendronic acid. Due to the risk of esophageal irritation, vomiting should not be induced. The patient should be in an upright position.

special instructions

Particular attention should be paid to any signs of adverse reactions in the esophagus. The patient should be informed about the possible risk of damage to the mucous membrane of the esophagus if the instructions for use are not followed and about the need to stop taking the drug Tevanat® and consult a doctor if dysphagia, pain when swallowing, chest pain, or the appearance or worsening of heartburn develops.

Due to the existing risk of irritation of the mucous membrane of the upper gastrointestinal tract, as well as aggravation of the underlying disease, it is recommended to be careful when prescribing the drug Tevanat® to patients with gastrointestinal diseases in the acute phase, incl. dysphagia, gastroesophageal reflux disease, gastritis, duodenitis, peptic ulcer of the stomach and duodenum, as well as recent (within the previous year) diseases of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, active bleeding from the gastrointestinal tract, surgery in the upper gastrointestinal tract, except pyloroplasty).

In patients with Barrett's esophagus, therapy with Tevanate should only be started after a careful assessment of the expected benefit versus the possible risk of developing esophageal cancer.

Cases of osteonecrosis of the jaw, usually associated with tooth extraction and/or local infection (including osteomyelitis), have been reported in patients with cancer receiving treatment regimens containing bisphosphonates (primarily IV). Many of these patients also received chemotherapy and corticosteroids. There have also been reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates. Before using bisphosphonates, patients with underlying risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroid therapy, poor oral hygiene) should undergo a dental examination with appropriate preventative dental treatment. Patients being treated with bisphosphonates should avoid invasive dental procedures whenever possible. In patients with osteonecrosis of the jaw who are on bisphosphonate therapy, dental surgery may worsen the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of bisphosphonates. Prescriptions and recommendations of the attending physician should be based on an individual assessment of the benefit/risk ratio for each patient.

If the patient forgot to take a Tevanat® tablet, it should be taken the next morning. You should not take 2 tablets. on day 1, you must continue to take 1 tablet. 1 time per week on the day that was chosen for administration from the very beginning of treatment.

In patients with hypocalcemia, hypovitaminosis D and hypoparathyroidism, it is necessary to carry out corrective therapy for disorders of mineral metabolism before starting treatment with Tevanat®. Due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in serum calcium and phosphorus concentrations may be observed during treatment. There are isolated reports of symptomatic hypocalcemia, sometimes severe, usually in patients with a predisposition to it (for example, hypoparathyroidism, vitamin D deficiency, calcium malabsorption).

There are reports of stress fractures of the proximal femur during long-term treatment with Tevanat® (from 18 months to 10 years). Fractures occurred after minimal or no trauma. Some patients first develop pain in the proximal femur and persist for weeks or even months before culminating in a femoral fracture. Often the fractures were bilateral, so if a patient has a fracture of one femur, it is necessary to monitor the condition of the other femur.

In patients taking Tevanat®, especially with concomitant therapy with corticosteroids, it is extremely important to ensure sufficient intake of calcium and vitamin D from food or in the form of medications.

Absorption of bisphosphonates is significantly reduced when administered concomitantly with food.

Impact on the ability to drive vehicles and work with equipment.

There was no effect on the ability to drive vehicles and work with equipment associated with an increased risk of injury.

Conditions for dispensing from pharmacies

On prescription.

Pharmgroups

Bone resorption inhibitor - bisphosphonate (correctors of bone and cartilage tissue metabolism)

Pharmaceutical actions

inhibiting bone resorption

Tevanate®

Due to the existing risk of irritation of the mucous membrane of the upper gastrointestinal tract, as well as aggravation of the underlying disease, it is recommended to be careful when prescribing the drug Tevanat® to patients with gastrointestinal diseases in the acute phase, including dysphagia, gastroesophageal reflux disease, gastritis, duodenitis , peptic ulcer of the stomach and duodenum, as well as recently suffered (within the previous year) diseases of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, active bleeding from the gastrointestinal tract, surgery in the upper gastrointestinal tract, except pyloroplasty).

In patients with Barrett's esophagus, therapy with Tevanate should only be started after a careful assessment of the expected benefit versus the possible risk of developing esophageal cancer.

There have also been reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates. Before using bisphosphonates, patients with underlying risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroid therapy, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment. Patients being treated for FD should avoid invasive dental procedures if possible. In patients with osteonecrosis of the jaw who are on FD therapy, dental surgery may lead to a worsening of the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of BF. Prescriptions and recommendations of the attending physician should be based on an individual assessment of the benefit/risk ratio for each patient.

An adverse event reported was osteonecrosis of the external auditory canal, which was predominantly associated with long-term use of alendronate. Possible risk factors for osteonecrosis of the external auditory canal include steroid use, chemotherapy, infection, and trauma.

If the patient forgot to take a Tevanat® tablet, it should be taken the next morning. You should not take two tablets on the same day, you should continue to take 1 tablet once a week on the day you chose to take from the very beginning of treatment.

In patients taking Tevanat®, especially with concomitant therapy with glucocorticosteroid drugs, it is extremely important to ensure sufficient intake of calcium and vitamin D from food or in the form of medications.

Absorption of BF is significantly reduced by simultaneous food intake.

Alendronate sodium (Tevanat): a modern effective drug for the treatment of osteoporosis

Osteoporosis (OP), a multifactorial polygenic skeletal disease, is the most common form of metabolic osteopathy. It is characterized by loss of bone mass, disruption of their microstructure (destruction/loss of trabeculae), decreased strength and is accompanied by a high risk of fractures. It is fractures - the consequences/outcomes of AP, the most severe of which are fractures of the femoral neck and radius in the lower third of the forearm (Colles fractures) - that determine the medical and medical-social significance of the disease, including increased mortality, and associated significant economic losses [1,2,4,6]. An important feature of AP is that this disease mainly affects elderly and senile people. The noticeable increase in the incidence of AP, observed since the second half of the twentieth century, naturally reflects the demographic changes occurring in the population and determined by the aging of the population in all industrialized and a number of developing countries of the world. Another, no less important feature of AP is its largely gendered (sexual) nature: more than 80% of all cases of AP are registered in elderly and old women, which reflects the undoubted role of the status of female sex hormones in maintaining the health of the skeletal system. It should be noted that modern ideas about the disease began to take shape in the 40s of the twentieth century, when the American endocrinologist F. Albright [5] described AP in postmenopausal women and suggested that its development is associated with estrogen deficiency. In the late 70s - early 80s. last century, another American endocrinologist, B. Riggs, based on data on changes in bone mineral density in different sexes and in different age groups, proposed to distinguish two main types of AP: postmenopausal and senile [12]. Subsequently, this first classification was deepened and supplemented. In clinical practice, AP occurs in a number of types and forms with fairly clear characteristics (Tables 1 and 2). Depending on the localization of the process in the bone structures, OP is morphologically divided into predominantly trabecular, cortical and mixed. Taking into account the etiology and characteristics of pathogenesis, primary and secondary AP are distinguished. Primary AP combines the two most common forms - postmenopausal AP (also called type I AP) and senile AP (type II), which together account for up to 85% of all cases of the disease. In addition, the group of primary AP includes relatively rare cases of idiopathic AP (including AP in men, AP of insufficiently clear etiology in adults), as well as juvenile AP. The etiology of primary AP, despite the undoubted connection with genetic causes and a number of risk factors (diet, lifestyle, etc.), remains unclear to date and is the subject of intensive research. Modern ideas about the pathogenesis of AP Bone tissue, despite its apparent stability, is a metabolically active, constantly renewed system. Throughout the life of an individual, remodeling cycles constantly occur in it, including two main processes: the destruction of the “old” bone, defined by the term “bone resorption,” accompanied by the destruction and removal of both mineral matter and organic matrix from the sites of resorption, and the subsequent process of formation of a new one bone, consisting of the synthesis of new bone matrix with its subsequent mineralization. Bone remodeling is aimed at: a) maintaining the mechanical integration of the skeleton under changing environmental conditions and b) releasing calcium during the resorption of the bone matrix and its entry into the blood, as well as the mineralization of the synthesized new matrix associated with the supply of calcium from the blood and the formation of the mineral component – hydroxyapatite, are an integral part of calcium homeostasis. Both processes of bone remodeling are balanced, which implies complete replacement of resorbed bone as part of its formation. Remodeling is carried out by two types of bone cells. The resorption process occurs with the participation of osteoclasts (OC) - mobile, multinucleated giant cells (diameter - 20-50 microns), having a corrugated edge (brush border) and forming tartrate-resistant acid phosphatase and other lysosomal enzymes that destroy the bone matrix. Another type of cell takes part in the formation of new bone - osteoclasts (OB), which are round cells with basophilic cytoplasm and an eccentrically located large nucleus. These cells have a developed endoplasmic reticulum, as well as a large number of free ribosomes, polysomes and mitochondria, and a well-developed lamellar complex. These structural features, together with the presence of receptors for a number of steroid, peptide and low-molecular biologically active substances (sex and calcemic systemic hormones, cytokines, prostaglandins, etc.) located on the plasma membrane and in the nucleus, determine the main functions of the OB. In these cells, the synthesis of matrix proteins (type I collagen, etc.) occurs, including those that form bone plates, proteins that regulate OC functions, as well as alkaline phosphatase, bone Gla-protein, a number of cytokines - growth and colony-stimulating factors - etc. Receptors for parathyroid hormone and female and male sex hormones are localized on the plasma membrane of the OB. Estrogens and corticosteroids inhibit the formation of OB. The activity of mature OB is stimulated by thyroid hormones, growth hormone, 1,25(OH)2D3 and inhibited by GCS. According to modern concepts, the process of bone remodeling is carried out as follows (Fig. 1). Activation of TC formation is initiated by the interaction of hematopoietic TC precursor cells with cells of the OB line, in which, in addition, pro-inflammatory cells (in particular T lymphocytes) participate. After the formation of the OC, a time-limited phase of bone resorption begins, then the process of its destruction is completed, the resulting cavity is covered with a layer of mononuclear cells (MB), and the phase of new bone formation (biosynthesis of the BM matrix) begins/starts, which is significantly longer in time than the resorption phase. The resorption cavity filled with new bone is covered with a layer of resting cells, which are walled up in it and turn into low-active cells - osteocytes - or undergo apoptosis. To regulate the formation of OCs and their resorbing activity during the physiological cycle of remodeling, contact between cells of the osteoblastic and osteoclastic lines is required. Monocyte-coline-stimulating factor (M-CSF) interacts with its receptor on OC, which causes stimulation of differentiation and proliferation of hematopoietic precursor cells of OC - pre-OC. An important role in the reactions of maturation, differentiation and proliferation of TC is played, on the one hand, by female sex hormones, estrogens, and on the other, by three members of the cytokine family - tumor necrosis factor and its receptor: the ligand of the receptor-activator of nuclear factor NF-kB, which is formed in OB (RANKL); the receptor-activator of nuclear factor NF-kB (RANK), synthesized in hematopoietic cells, activates the differentiation of TCs and supports their functions. OB also form the third member of this family, osteoprotegerin (OPG). The interaction between RANKL and RANK, leading to the activation of NK-kB in OB precursor cells, is the essence of the process of activation of the formation of bone-resorbing cells - OC, their differentiation, proliferation and maturation. It is important to note that, as is the case with many other body systems, the skeletal system also contains a natural regulator of the process of activation of the formation of mature OCs and their bone-resorbing effect. This cytokine-regulator, OPG, formed in the OB, is a decoy receptor that blocks the interaction between RANKL and RANK and the formation of mature OC, thereby exerting an antiresorptive effect. The above-mentioned role of estrogens in the processes of bone remodeling consists of influencing the formation of cytokines by T cells, modulating the biosynthesis of RANKL and OPG by stromal and osteoblastic cells, a direct inhibitory effect on the differentiation of TC and a stimulating effect on OB, leading to an increase in the formation of new bone in response to mechanical loads acting on the skeleton [6,14]. An imbalance between the processes of bone remodeling and the prevalence of bone resorption over the process of new bone formation is a central link in the pathogenesis of AP. It is believed that this imbalance reflects a violation of the basic mechanisms of systemic hormonal and local (cytokine) regulation of bone cell activity in genetically predisposed individuals. In conditions of progressive estrogen deficiency in the pre- and especially postmenopausal periods (women), somato- and andropause (women and men), calcium metabolism disorders in response to vitamin D deficiency and secondary hyperparathyroidism (senile AP, women and men), decreased production of OPG , the process of bone resorption is activated, and the process of new bone formation is significantly reduced and slowed down. Pharmacotherapy of AP Treatment of AP includes both non-pharmacological (physical activity, balanced diet, fall prevention, etc.) and pharmacological methods using drugs. To treat AP, several groups of drugs with different directions and different mechanisms of action are used [3,4]. In accordance with the main direction of action, they include: antiresorptive drugs, which primarily suppress the process of bone resorption, drugs that stimulate the process of new bone formation. In addition, there is a group of drugs that have a normalizing effect on the balance of bone remodeling disturbed in AP and have both antiresorptive and bone-forming properties. Antiresorptive agents are represented by bisphosphanates (BP), hormone replacement therapy for menopausal disorders (estrogen and estrogen-progestin drugs, tibolone, selective estrogen receptor modulators), calcitonins, the RANKL blocker - denosumab, vitamin D and its active metabolite [4]. Bone-forming agents include parathyroid hormone preparations and its fragments (teriparatide, etc.), strontium ranelate, anabolic steroids, vitamin D preparations and its active metabolite. Bisphosphonates Bisphosphonates (BP) represent a quantitatively quite large group (>15) of antiosteoporotic drugs with antiresorptive action, the first drugs of which were introduced into medical practice more than about 20 years ago. Currently, BP is considered as the main group of antiosteoporetic drugs. The discovery of BP and their use for the treatment of AP is associated with the name of the Swiss pathophysiologist and pharmacologist Herbert Fleisch (University of Bern, Switzerland), who, together with his colleagues, in the mid-60s of the twentieth century. discovered in the body a substance with an inorganic structure - pyrophosphate, which actively binds to calcium salts (in particular, to the mineral component of bone hydroxyapatite), disrupting the formation of their crystals and preventing dissolution. BFs are synthetic analogues of pyrophosphate, which, unlike it, are resistant to the action of hydrolytic enzymes in the gastrointestinal tract, in the structure of which the central oxygen atom (–O–) is replaced by a carbon atom (–C–) (Fig. 2). The indicated structure of the central part of the BF molecule suggests the possibility of creating various structures on its basis due to the addition of side chains and esterification of acid phosphate groups. In accordance with the structure of the side chains, the classification of BF divides them into two subgroups: 1) substances that do not contain an amino group (clodronate, tiludronate, etidronate), belonging to the first generation of BF, and 2) having a longer side chain, including amino or aromatic groups ( alendronate, pamidronate, risedronate, ibandronate, zoledronate, etc.), the drugs of which belong to the 2nd and 3rd generations of BP (Fig. 2). These drugs, often called aminobisphosphanates, are significantly superior in antiresorptive activity to drugs that do not contain an amino group. Mechanism of action of BF The main pharmacological effect of BF is manifested in the inhibition of bone resorption, i.e. one of the processes of bone remodeling carried out by bone-resorbing cells - OK. And the main target of action of BF in the body is OK. The peculiarities of the chemical structure of these drugs (the presence of phosphate groups and side chains in the structure of their molecules) determine the mechanisms necessary for this. The first of them is that, due to a very high affinity for the mineral substance of bone - hydroxyapatite - BFs strongly bind to it and create high concentrations, primarily at those points of the skeleton where remodeling processes actively occur. Due to this strong binding, BP prevents the destruction of hydroxyapatite crystals, which give bone strength. Another aspect of the action of BP is associated with the suppression of OC activity. BF molecules bound to hydroxyapatite are located in close proximity to these cells. In this case, the antiresorptive effect is realized with the participation of different mechanisms in BPs containing and not containing amino groups in the side chains of the molecule. In the case of drugs that do not contain an amino group (ethindronate, etc.), after the capture of OC, they are incorporated into adenosine triphosphate (ATP) molecules due to a reaction carried out with the participation of the enzyme aminoacyl-transferRNA synthetase. The intracellular accumulation of these non-hydrolyzable ATP analogues has a cytotoxic effect on OCs, because they inhibit a number of ATP-dependent biochemical reactions in the cell, which leads to TC apoptosis. Amino-BP (alendronate, etc.) also cause apoptosis of the OB, but through a different mechanism: penetrating into the OB, they bind to the enzyme farnesyl-pyrophosphate synthetase and suppress its activity. This enzyme plays a key regulatory role in the mevalonic acid cascade, the end product of which is the biosynthesis of cholesterol, as well as other sterols and isoprenoid lipids. Inhibition of the activity of farnesyl-pyrophosphate synthetase under the influence of amino-BP leads to disruption of post-translational modification (isoprenylation) of proteins, including small guanidine triphosphate-binding proteins Rab, Rac and Rho, which play a central role in the main functions of OC: the formation of fibrous structures of actomyosin, necessary for cell movement, corrugated edge of the OC, due to which cells attach to the resorbable surface of the bone, as well as participating in other reactions. Violation of the formation of the listed proteins causes apoptosis of TC (Fig. 3). BF in the treatment of AP BF are used to treat all types and forms of AP. They are widely used for the most common type of disease – postmenopausal AP. The use of this group of drugs is due to their high antiresorptive activity due to their suppressive effect on OC. Clinically, the therapeutic effect of BF is manifested by a decrease in the incidence of fractures, biochemically by a decrease in blood and urine markers of increased bone resorption and a morphologically expressed increase in bone mineral density (BMD) to varying degrees, preservation or even formation of new trabeculae with the deposition of mineral deposits, and an increase in the number of structural bone units , which have reached the maximum degree of mineralization [14,16]. Among BFs prescribed for oral administration, the most convincing data regarding the prevention of fractures were obtained for alendronate and risedronate, treatment of which led to a statistically significant decrease in the number of vertebral fractures [6,7,10] and hip fractures [11], and a decrease in the number of deformities vertebral bodies and slowing down the decline in height in women with postmenopausal type of AP [1,4,11]. Ibandronate has been shown to significantly reduce the incidence of vertebral fractures [1,6]. The relative risk of fractures of different locations with 3-year use of modern amino-BPs is presented in Table 3. BPs also have a therapeutic effect in other types and forms of AP, in particular in steroid-induced or immobilization-induced AP, as well as in Paget’s disease and others. Alendronate alone One of the most effective, widely and long-term BP drugs used for the treatment of AP is alendronate, which belongs to the amino-BP group. It was developed (USA) and introduced into practice in 1993 under the trade name Fosamax®. Alendronate is one of the most active antiresorptive drugs. The mechanism of its action, as in the case of other amino-BPs, is the inhibition of the enzyme farnesyl-pyrophosphate synthetase, caused by this violation of the prenylation of proteins important for the functioning of OC, which causes apoptosis of these cells and inhibits bone resorption. Alendronate is absorbed to a limited extent from the gastrointestinal tract. Its bioavailability in men (10 mg tablets) when taking on an empty stomach 2 hours before breakfast is 0.59% and is close to bioavailability in women (0.78%). When administering the drug for 0.5 and 1 hours before breakfast, bioavailability is reduced by about 40% compared to taking 2 hours before breakfast. The intake of Alendronate inside, during or 2 hours after breakfast, also has a negative effect on the absorption of the drug. Reception along with coffee or orange juice reduces the specified indicator by 60%. After absorption, a rapid (30-60 minutes) distribution of alendronate into soft tissues is observed with subsequent redistribution in the bone or excretion in the urine. The concentration of the drug in the blood plasma after taking the therapeutic dose orally is very small (approximately 5 ng/ml), its binding with plasma proteins reaches 78%. About 40–60% of the dose entered in the systemic circulation is concentrated in the skeleton depending on the rate of remodeling processes flowing in it. The non -permanent part is excreted by the kidneys. Alendronate is not subjected to human and animals of metabolization in the body and is found in the urine unchanged. The drug entering the bone tissue is firmly binded to hydroxyapatitis, which determines its long -term, for several years in the skeleton (the period of the age of the Alendronate associated with the bone is about 10 years) [14]. This is also facilitated by the fact that even with the destruction of the bone matrix in the process of remodeling, the released BF is re -binded to indestructible hydroxyapatitis crystals. The main indication for the prescription of alendronate is the treatment of postmenopausal, senile and steroid OP, as well as the disease of pedget and hypercalcemia due to malignant neoplasms. The drug is used in tablets in doses of10 mg/day. or 70 mg 1 time/week. Dose 10 mg/day. With the simultaneous addition of calcium preparations causes a decrease in bone resorption markers after 3 months. and an increase in the levels of markers of bone formation by 6 months. treatment. The use of the drug causes a statistically reliable increase in the MPC in different skeletons [1,3,6,10,11,15,16] and reduces the number of fractures of vertebral bodies, fractures of the femoral cervix and extra -reconstructive fractures of a different localization (Fig. 4) [1.11) [1.11 ]. It was established that in accordance with the therapeutic effect, its daily intake at a dose of 10 mg corresponds to the reception at a dose of 70 mg 1 time/week. [1.13]. The creation of a dosage form of alendronate in the form of 70 mg tablets and its detailed study was due to the need to increase the compliance of this type of therapy. Due to the fact that the treatment of OP is a very difficult and long process, as in the case of other chronic diseases, and the desire and opportunity of patients to follow the doctor’s prescription (i.e. medical recommendations), which is actually and is The content of the term "compliance" is far from ideal. A significant part of patients (according to various sources, from 25 to 50%) are incorrectly taken by drugs, independently decides to stop treatment, etc., which causes a decrease/absence of the therapeutic effect, the development of adverse reactions and can contribute to noticeable progression of the disease. One of the reasons for the low compliance of therapy is the inconvenient regime of drug dosing, for example, involving 2-3 - often the introduction of drugs per day, the need for a clear observance of the diet, etc. Moreover. Moreover, in the case of alendronate, which, like other drugs from the BF group in accordance With the requirement of instructions for medical use, they take on an empty stomach, in 30 minutes. Before breakfast, drink it with 1 glass of water, observe the vertical position of the body (sitting or standing) for at least 30 minutes. Alendronate tablets of 70 mg with a reception of 1 time/week. Significantly increased the adherence of patients (compliance) of therapy for OP primarily due to the convenience of using the drug. In general, Alendronate has good tolerance. Nevertheless, with its use in some cases, irritation of the mucous membrane of the upper gastrointestinal tract, ulceration of the mucous membrane of the duodenum, abdominal pain, dynopeptic disorders: constipation, diarrhea, nausea, vomiting, dystonia, dystonia of the stomach, Melena, and the gastric contained are observed. In the esophagus, as well as bone, muscle, articular and headaches. The seizures of the mucous membrane of the esophagus, mouth and pharynx, esophagitis, erythema skin, osteonecrosis of the lower jaw, flu -like fibrillation syndrome, and renal toxicity, and utilizers include very rare, unit complications of therapy with alendronate. It should be noted that the reception mode 1 time/week. Increased patients with treatment and improved the tolerance of the drug. High clinical efficiency and generally good tolerance of alendronate in the treatment of OP served as the basis for including the drug in the list of drugs included in the federal guidelines for the use of drugs of the Ministry of Health and Social Development in 2005-2009, in the list of vital and most important drugs of the Ministry of Health and Social Development for 2010 for 2010 , as well as in the clinical recommendations of the Russian Osteoporosis Association “Osteoporosis. Diagnosis, prevention and treatment ”(2009). In 2008, Tevanat expired the duration of the Alendronate of the Alendarnate of the Ooriginator and the United States, and then in other countries the first generic Alendronate preparation, developed by the pharmaceutical company Teva, called Tevanate, was registered and permitted for medical use. In addition to the United States and Russia, Tevanat is permitted for medical use in 21 countries of the European Union. The dosage form - Tevanate tablets contain 70 mg of alendronate (in the form of monohydrate sodium salt of alendronic acid). The composition of the tablets and their mass differs from the corresponding indicators for Fosamax®. When creating this dosage form, the task was to improve the tolerance of the drug and reduce the risk of developing a sufficiently characteristic of BF in general and for alendronate in particular the side effect - damaging effects on the mucous membrane of the esophagus and stomach (observed in approximately 1.5% of patients). According to the existing experimental and clinical data, damage to the mucous membrane of the esophagus and the antrum of the stomach with the oral use of the BF can be associated with the adhesion of the tablet, its dissolution with the formation of a gel from the dosage form of the auxiliary substances, to an even greater extent fixing alendronate on the mucous membrane of A logical increase in the concentration of the drug in a small area (especially if it is thrown into the esophagus of the acidic contents of the stomach), due to which local irritation/inflammation is formed, manifested by symptoms of esophagitis. The causes of this phenomenon are largely related to the dosage form: its size, shape and composition of excipients. Tevanate is an original tablet form of alendronate, which differs from Phosamax®: a) smaller sizes and mass (200 mg and 350 mg, respectively); b) a different composition of excipients, which are well dissolved without preliminary swelling with the formation of sticky gel. The indicated properties determine the free passage of the pill through the esophagus, which contributes to its watering with 1 glass of water, a slight risk of sticking to the mucous membrane in the gastrointestinal tract and the development of esophagitis phenomena. The main indications for the appointment of Tevanate are the treatment of OP in postmenopaus women in order to prevent fractures, including thigh fractures and compression vertebrae fractures; Treatment of senile OP in men and women, as well as steroid OP and Pedget's disease. The use of the drug is contraindicated in hypocalcemia, conditions that make it difficult to pass through the esophagus (including strictures or esophagus ahalasia), the patient’s inability to stand or sit directly for at least 30 minutes, and a severe renal (creatinine clearance is less than 35 ml/min. .), severe violations of mineral metabolism, increased sensitivity to the components of the drug. Tevanat, in addition, is not used in children, during pregnancy and during lactation. When conducting the course of Tevanate, it is necessary to carefully monitor the correctness of taking the pills by the patient, the possibility of any signs of the occurrence of adverse reactions from the esophagus, with caution to use it in patients with the concomitant pathology of the gastrointestinal tract in the exacerbation phase, with hypovitaminosis D. During the treatment period, it is necessary to ensure adequate intake D and calcium (at least 1–1.2 g/day). Tevanate simultaneous in time with calcium drugs, antacids or other drugs for oral use is not allowed due to a possible decrease in the absorption of alendronate. In this regard, it is necessary to observe the temporary interval at least 30 minutes. After taking tevanate and taking other drugs inside. It should be noted that the use of alendronate goes well with other drugs used in the treatment of concomitant pathology, in particular its purpose of 70 mg once a week in patients receiving non -steroidal anti -inflammatory drugs, does not lead to an increase in the frequency of undesirable phenomena by the gastrointestinal tract [ 9]. At the same time, comprehensive treatment in some cases has undoubted advantages over monotherapy OP. Thus, data were obtained indicating the appropriateness of the combined use of alendronate and vitamin D (calcitriol, alphakaltsidol, etc.) in patients with a high risk of falls and related fractures [15].

Literature 1. Osteoporosis /ed. O.M. Lesnyak, L.I. Benevolenskoy. – 2nd ed., revised. and additional – M.: GEOTAR-Media, 2009. – 272 p. – (series “Clinical Guidelines”). 2. Rozhinskaya L.Ya. Systemic osteoporosis. 2nd edition, revised, additional, M.: Mokeev Publishing House, 2000. – 195 p. 3. Rozhinskaya L.Ya., Rodionova S.S. The role of active metabolites of vitamin D in the pathogenesis and treatment of metabolic osteopathies. M.: 1997, 38p 4. Schwartz G.Ya. Pharmacotherapy of osteoporosis. – M.: Medical Information Agency, 2002.–368 p. 5. Albright F., Bloomberg F., Smith PH Postmenopausal osteoporosis. //Trans. Assoc. Am. Physician. – 1940. – 55. – 298–305. 6. Bock O., Felsenberg D. Bisphosphonates in the management of postmenopausal osteoporosis – optimizing efficacy in clinical practice. //Clin/Interv.Aging, – 2008.–3(2).– 279–297. 7. Boivin GY, Chavassieux PM, Santora AC et al. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women.//Bone.–2000. – 27(5).– 687–694. 8. Carr AJ, Thompson PW, Cooper C. Factors associated and persistence to bisphosphonate therapy in osteoporosis: a cross-sectional survey.//Osteoporosis Int.–2006.–17(6). –1638–1644. 9. Cryer B., Miller P., Petruschke R. et al.Upper gastrointestinal tolerance of one weekly alendronate 70 mg with concomitant non-steroidal anti-inflammatory drug use. //Aliment.Pharmacol.Ther. – 2005.–21(5).–599–607. 10. Drake M., Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. //Mayo Clin.Proc., 2008. – 83(9).–1032–1045. 11. Papapoulos SE, Quandt SA, Liberman UA et al. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. //Osteoporosis Int.–2005.–16(5): 468–474. 12. Riggs BL, Wahner HW, Seeman E. et al. Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes.//J/Clin/Invest.–1982.–70.–716–723. 13. Rizoli R, Greenspan SL, Bone G et al. Alendronate Once–Weekly Study Group/ Two–year results of once–weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis/ // J.Bone Miner.Res.–2002.–17(11).–1988–1996. 14. Russell RGG Bisphosphonates: mode of action and pharmacology. //Pediatrics.–2007.–119.–S150–S162. 15. Schacht E., Dukas L., Richy F. Combined therapies in osteoporosis: bisphosphonates and vitamin D–hormone analogs.//J.Musculoskelet.Neuronal.Interact.–2007.–7(2).–174–184. 16. Shoback D. Update in osteoporosis and metabolic bone disorders. //J Clin Endocrin Metab., 2007.–92, 747–753.

Tevanat, 70 mg, tablets, 4 pcs.

In patients with Barrett's esophagus, therapy with Tevanate should only be started after a careful assessment of the expected benefit versus the possible risk of developing esophageal cancer.

Absorption of bisphosphonates is significantly reduced when administered concomitantly with food.

Impact on the ability to drive vehicles and work with equipment.

There was no effect on the ability to drive vehicles and work with equipment associated with an increased risk of injury.

Tevanat instructions for use

Pharmacological action The action of Tevanat is based on the therapeutic effect of alendronic acid on the body. The drug slows down the process of bone tissue destruction, reducing the activity of osteoclasts. When using Tevanat, the rate of resorption slows down, which allows its mineral composition to be restored. Under the influence of the medication, the histological structure of the bone tissue of the spine and skeleton is normalized. Indications for use Tevanat is recommended for use in women with postmenopausal osteoporosis for the prevention of spinal fractures under compression and femoral neck fractures.

Directions for use Tevanat tablets are recommended to be taken orally half an hour before breakfast, the first drink and other medications. After taking the tablet, you should drink plenty of drinking water without gas and stay in an upright position for at least 30 minutes - walking, standing, sitting. Tevanat is prohibited from chewing or biting. You should not take the drug at night, before getting out of bed in the morning, or in other conditions in which the patient will lie down for a long time. Tevanat should be taken 1 tablet once a week. If a pill is missed, the medication should be taken on the second day. Further treatment is carried out according to the recommended regimen of 1 ruble/week. It is forbidden to take 2 tablets at the same time.

Side effects When using the medication, abdominal pain, sour belching, symptoms of dyspepsia, stool upset, dysphagia, ulceration of the esophageal mucosa, bone pain, myalgia, arthralgia, convulsions, headache, taste disturbances often occur. Infrequently, treatment with Tevanat is accompanied by nausea, gastritis, esophagitis, esophageal erosions, gastrointestinal ulcers accompanied by bleeding. Rarely, the use of the medication causes a flu-like syndrome in the patient at the beginning of treatment, stricture of the esophagus, uveitis, episcleritis, scleritis, ulceration of the mucous membrane of the oral cavity and pharynx, perforation of the esophagus, bleeding of the upper gastrointestinal tract, osteonecrosis of the jaw in people with oncological pathologies taking bisphosphonates, symptomatic hypocalcemia and hypophosphatemia. It is extremely rare to develop a stress fracture of the proximal femur during treatment with Tevanat. Allergic reactions when using Tevanat may include rash, itching, photosensitivity, urticaria, angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Contraindications Tevanat should not be taken by patients who are allergic to the components of the tablets. The drug is contraindicated in case of hypocalcemia, diseases of the esophagus in which the movement of food is impaired (achalasia, strictures), severe kidney disease (creatine clearance below 35 ml/min), severe disorders of mineral metabolism. Tevanat tablets are not recommended for people who are unable to stand or sit for half an hour. It is prohibited to use the medication to treat children. The drug can be used with caution in cases of relapse of chronic gastrointestinal diseases (Barrett's esophagus, dysphagia, gastritis, ulcers, duodenitis, gastroesophageal reflux disease) and vitamin D deficiency.

Pregnancy Tevanat is contraindicated in pregnant women and breastfeeding mothers.

Drug interactions The bioavailability of alendronic acid is reduced when Tevanate is taken with foods and drinks containing calcium (juices, milk, mineral water), food additives, antacids and other medications. The interval between taking other medications, food and drinks should be at least 30 minutes. When treating Tevanat with estrogen and prednisolone, no significant interaction is observed. When using Tevanat during therapy with NSAIDs, the risk of developing severe gastrointestinal lesions increases.

Overdose Exceeding the dose of Tevanat is expressed by hypocalcemia, hypophosphatemia, stool upset, heartburn, esophagitis, gastritis, and the development of ulcers of the digestive system. To eliminate the symptoms of overdose, the patient should take milk or antacids containing calcium.

Release form Tevanat is produced in the form of flat tablets for internal use, 70 mg of alendronic acid. The white or off-white tablets are individually engraved with a “T” on one side. The tablets are packaged in blisters of 4 pcs. One package may contain 1 or 3 blisters with medication.

Storage conditions: In a dark place in conditions not exceeding +30 degrees Celsius.

Composition Tevanat tablets are made on the basis of alendronic acid using MCC, croscarmellose sodium and magnesium stearate.

Pharmacological group Medicines used to correct disorders that occur during menopause

Nosological classification (ICD-10) Postmenopausal osteoporosis (M81.0)

Active ingredient: alendronic acid

ATX: M05BA04

Manufacturer: Teva

Additional information about the manufacturer Country of origin – Israel.

Additionally, in patients taking Tevanate and bisphosphonates, osteonecrosis of the jaw often develops after invasive dental procedures, complicated by osteomyelitis or without complications.