Miacalcic solution and spray: instructions for use, price, reviews and analogues

Pharmacodynamics and pharmacokinetics

Miacalcic contains the active ingredient calcitonin , which is a hormone produced by C-cells located in the thyroid gland. This hormone is characterized by antagonism to parathyroid hormone and, in parallel with it, takes part in regulating calcium metabolism in the human body.

The structure of all calcitonins is one chain consisting of 32 amino acids , as well as a ring, including 7 amino acid residues located at the N-terminus, with different sequences depending on the species. Due to the higher affinity of salmon calcitonin for the corresponding receptors (compared to mammalian calcitonins ), the strength and duration of its action are more pronounced.

Due to the influence of salmon calcitonin osteoclast activity is inhibited , which leads to a significant decrease in the metabolic rate in bone tissue and, in painful conditions characterized by increased resorption (for example, osteoporosis ), brings it to a normal level. Also noted is the analgesic effect of Miacalcic in relation to pain syndrome of bone origin, which appears, apparently, due to the direct effect of the drug on the central nervous system.

Already with a single use of the medicinal product Miacalcic in the form of an injection solution or nasal spray, the patient experiences a biological, clinically significant response, manifested by an increase in the excretion of calcium , sodium and phosphorus (due to weakening of tubular reabsorption ) and a decrease in the excretion of hydroxyproline .

Long-term intranasal or parenteral administration of Miacalcic leads to a significant decrease in the content of biochemical markers inherent in bone metabolism, including pyridinoline , bone alkaline phosphatase isoenzymes and serum C-telopeptides .

Parenteral administration of calcitonin reduces exocrine and gastric pancreatic secretion , which determines the effectiveness of Miacalcic in the treatment of acute pancreatitis .

When using Miacalcic nasal spray, there is a statistically significant increase (1-2%) mineral density in the lumbar vertebrae, determined in the first year of therapy and maintained for 5 years. In the femur, Miacalcic helps maintain normal mineral density .

The use of Miacalcic spray in a daily dosage of 200 IU led to a clinically and statistically significant decrease (36%) in the risk of fresh vertebral fractures , which was noted in the group of patients receiving combinatorial treatment with Miacalcic, calcium and vitamin D , in comparison with the group of patients receiving calcium supplements , vitamin D and placebo . In addition, in patients of the first group, a decrease in the incidence of multiple fractures of the spinal vertebrae by 35%.

With subcutaneous and intramuscular administration, the bioavailability of salmon calcitonin is approximately 70%, with intranasal application (in the nasal cavities) - 3-5%, in relation to the parenterally administered drug. Plasma Cmax with intramuscular administration is achieved within 60 minutes, with subcutaneous injection within 23 minutes, with intranasal administration, on average, after 10 minutes.

The apparent VSS of the drug is 0.15-0.3 l/kg. Binding to plasma proteins occurs by 30-40%. Up to 95% of calcitonin and its metabolic products are excreted by the kidneys, while only 2% of the active ingredient is excreted in unchanged form. T1/2 with intramuscular injection takes approximately 60 minutes, with subcutaneous injection - 60-90 minutes, with intranasal administration - 20 minutes.

With repeated intranasal injections of the drug, the accumulation of its active ingredient does not occur. In the case of using doses of Miacalcic that exceed the recommended ones, its higher concentrations are found in the plasma (as confirmed by an increase in AUC), while the relative bioavailability of the drug does not increase. Penetration of the drug through the placental barrier is not observed.

Determination of the plasma content of salmon calcitonin , like other polypeptide hormones , is not an indicator of its effectiveness, which should be determined by clinical indicators of the productivity of the therapy.

The role and place of Miacalcic in the treatment of osteoporosis

The medical and socio-economic significance of AP is determined by its consequences - fractures of the vertebral bodies, femoral neck and radius in a typical location, which are one of the most common causes of disability in the elderly. Epidemiological studies reveal a high incidence of osteoporosis. Bone loss in osteoporosis occurs gradually, insidiously, and is often diagnosed after fractures, making osteoporosis a “silent epidemic.” According to LJ Melton, in the United States with a population of 240 million people, low bone mineral density (BMD) is found in 18.6 million people, of which about 10 million suffer from osteoporosis (the ratio of men to women is 1:5). After age 50, up to 30% of white women have osteoporosis in either the proximal femur, lumbar spine, or distal forearm [1]. The prevalence of AP in the UK, Portugal and other European countries is similar to that in the US. In Russia there are only a few works on the epidemiology of osteoporosis. In a survey of Moscow residents over 50 years of age, AP was found in 33.8% of women and 26.9% of men, and osteopenia – in 43.3 and 44.1%, respectively [2]. In another study conducted in Moscow, out of 2155 women aged 55 years and older, AP of the lumbar spine was detected in 29.8% of the examined individuals, and osteopenia – in 43.3% [3]. Mortality within the first year after a proximal femur fracture is almost 40% [4–7]. The highest incidence of hip fractures is observed in the American population, as well as in the Scandinavian countries, Great Britain and Belgium (for example, in Sweden 1391 per 100,000 population), and relatively low in South Africa and New Zealand (in South Africa 26 per 100,000 population) [8, 9]. Our study in St. Petersburg revealed similar figures for the prevalence of OP. When conducting an osteodensitometric study using X-ray absorptiometry (lumbar spine and proximal femur) of 660 women (average age 62.2±7.4), osteoporosis was identified in 214 (32.4%) subjects, osteopenia - in 245 (37.1 %), and 201 (30.5%) women had normal values of bone mineral density. When distributing women by age group, a direct relationship between age and OP was revealed (Table 1). According to WHO experts, by 2050, the incidence of hip fractures associated with osteoporosis will increase from 1.7 million cases per year to 6.3, which will entail a sharp increase in the economic costs of treating this pathology [10]. According to various studies (family, twin), the contribution of genetic disorders reaches 70–80%; the remaining 20–30% are due to environmental factors [11–13]. Classification of osteoporosis A. Primary osteoporosis • Postmenopausal osteoporosis (type 1) • Senile osteoporosis (type 2) • Juvenile osteoporosis • Idiopathic osteoporosis B. Secondary osteoporosis I. Diseases of the endocrine system (endogenous hypercortisolism, thyrotoxicosis, hypogonadism, hyperparathyroidism, type 1 diabetes mellitus, hypopituitarism, polyglandular endocrine insufficiency). II. Rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis). III. Diseases of the digestive system (resected stomach, malabsorption syndrome, chronic liver diseases). IV. Kidney diseases (chronic renal failure, renal tubular acidosis, Fanconi syndrome). V. Blood diseases (myeloma, thalassemia, systemic mastocytosis, leukemia and lymphoma). VI. Other diseases and conditions (immobilization, oophorectomy, chronic obstructive pulmonary diseases, alcoholism, anorexia nervosa, eating disorders, organ transplantation). VII. Genetic disorders (osteogenesis imperfecta, Marfan syndrome, Ellers-Danlos syndrome, homocystinuria and lysinuria). VIII. Medicines (corticosteroids, anticonvulsants, thyroid hormones, immunosuppressants, gonadotropin-releasing hormone agonists, aluminum-containing antacids). According to morphological criteria, they are distinguished: trabecular, cortical and mixed OP. According to metabolic activity: OP with high bone turnover, low bone turnover and normal bone turnover. The process of modeling bone tissue is negatively affected by malnutrition (malnutrition, anorexia), bad habits (smoking, alcohol), diseases leading to limited physical activity, late puberty, and hypogonadism. Bone resorption also increases with immobilization, excess production of parathyroid hormone, thyroid hormones, and calcium and vitamin D deficiency. The following should be considered as the main causes of AP: 1) low peak bone mass, caused by genetic factors and poor nutrition in childhood and adolescence; 2) early loss of peak bone mass during early menopause, after oophorectomy, and with the development of various endocrine diseases; 3) acceleration of bone loss with the use of various medications, reduced physical activity, immobilization, after transplantation, with systemic immunoinflammatory diseases, etc. For a long time, AP is asymptomatic and is manifested only by skeletal bone fractures. Most patients have complaints of constant back pain, which intensifies with minor static loads and prolonged stay in one position. These pains may be relieved by lying down and resting. The cause of pain can also be periosteal hemorrhages and reactive muscle tension. Fractures of the vertebral bodies are manifested by a decrease in height and the formation of kyphosis or hyperlordosis of the lumbar spine. For instrumental assessment of bone mass, radiography and bone densitometry are currently used. Standard radiography makes it possible to assess the severity of AP based on increased transparency and disappearance of transverse trabeculae in the vertebral bodies, thinning and increased contrast of the endplates, and thinning of the cortical layer. A sign of a compression fracture of the vertebral body is a decrease in the height of the vertebral body, the appearance of a wedge-shaped, biconcave deformity (fish vertebrae). The morphometric approach is also used to assess the incidence of new cases of asymptomatic vertebral fractures (20% level of decrease in vertebral body height or 4 mm or more). Unfortunately, the sensitivity of the method is low for diagnosing osteopenia and initial forms of osteoporosis. Currently, bone densitometry methods are used for early diagnosis of AP, of which the most universal is dual-energy X-ray absorptiometry (DEXA), which allows measuring bone mineral density (BMD) in any part of the skeleton. By means of X-ray densitometry, two quantities are measured: the projection area of the area under study (in square centimeters) and the mineral content (in grams), from which the BMD is then calculated (in g/cm2). To assess changes in BMD in a patient compared to the norm, two criteria have been developed - T and Z. According to the Z-criterion, the patient’s BMD is compared with the average statistical norm for the same age, and according to the T-criterion - with the norm corresponding to the peak of bone mass, i.e. e. 30–35 year olds. In both cases, the result is expressed in standard square deviations (SD) from the reference norm. The lumbar spine (L1–L2), proximal femur, and distal forearm bones are the most commonly used for diagnosing AP. According to WHO recommendations, osteoporosis is characterized by a decrease in BMD by more than –2.5 standard deviations (SD) according to the T-criterion, and the presence of at least one fracture indicates severe osteoporosis. In osteopenia, BMD is between –1.0 and –2.5 SD from peak bone mass. Ultrasound densitometry should currently only be used for screening studies. Indications for determining bone mineral density are as follows: • Postmenopausal women under the age of 65 with risk factors. • Women aged 65 years and older. • Men aged 70 years and older. • Adults with fractures with minimal history of trauma. • Adults with diseases or conditions that cause low bone mass, especially women 45 years of age and older and men 60 years of age. • Adults taking medications that reduce bone mass. • Monitoring the effectiveness of osteoporosis treatment. Some invasive methods can provide important information about bone turnover. Histomorphometric analysis of the iliac crest provides information about the rate of bone formation at the cellular and tissue levels, but the assessment of bone resorption by this method is less accurate. Finally, bone metabolism and bone formation can be inferred from the extent of skeletal uptake of isotope-labeled bisphosphonates, but the sensitivity of this method has not yet been determined. Certain biochemical markers are used to assess bone turnover. Biochemical markers of bone formation, which are products of osteoblast activity, are represented by bone alkaline phosphatase (BALP), osteocalcin (OC), carboxy(C)- and amino(N)-terminal propeptides of type I procollagen (C-PPI and N-PPI). Biochemical markers of bone resorption are mainly fragments of type I collagen degradation (N- and C-telopeptides, pyridine cross-links of collagen, including pyridinoline (PIR), deoxypyridinoline (DPIR), hydroxyproline (OP), galactosyl-hydroxylysine (Gal-Hyl), as well as non-collagenous proteins (bone sialoprotein (BSP) and bone acid phosphatase (AP)). These markers can be determined in urine or in serum. It should be noted that the levels of these markers can be influenced not only by the rate of bone turnover, but also by other factors (exercise, nutrition, menstrual cycle, etc.) Bone markers are used both to detect remodeling disorders and to monitor therapy Prevention of osteoporosis According to the official opinion of the European Osteoporosis Society (EFFO), the prevention of OP should be a priority in healthcare development.The development of a global strategy for controlling the incidence of AP includes three main areas: prevention, treatment and examination [14,15]. The main measures for the prevention of AP and fractures include: providing adequate nutrition with sufficient calcium intake and supplementation if necessary, as well as phosphorus, magnesium, copper, zinc, vitamins C and K, which are involved in the process of bone formation. Additionally, vitamin D is prescribed, the combination of which with calcium is considered optimal. It is necessary to eliminate bad habits: smoking and alcohol abuse. Pharmacotherapy is indicated for both primary and secondary prevention of AP. Treatment of osteoporosis The main goals of treatment for AP are: – preventing the occurrence of new bone fractures; – slowing down or stopping the loss of bone mass (ideally, its growth); – normalization of bone remodeling processes; – reduction of pain, expansion of motor activity; – improving the patient’s quality of life. All means of pathogenetic therapy and prevention of AP are divided into three groups according to the predominant mechanism of action: – agents that primarily inhibit bone resorption: salmon calcitonin (Miacalcic), bisphosphonates, strontium ranelate, estrogens, selective estrogen receptor modulators (SERMs), calcium; – drugs that stimulate bone formation: parathyroid hormone, strontium ranelate, growth hormone, androgens, fluorides; – preparations of multifaceted action: vitamin D and its active metabolites, ossein-hydroxyapatite complex. Calcitonin (CT). Calcitonin is a peptide hormone secreted primarily by parafollicular C cells of the thyroid gland. Although this hormone has been isolated from more than 15 species of animals, the synthetic CT of salmon is currently the most widely used. It has 20–40 times higher biological activity than porcine and human CT. Salmon CT has been used to treat AP for over 30 years and is available in both injectable and intranasal forms. For patient convenience, an oral form of CT is currently under development. The main biological effect of CT is the suppression of bone resorption due to a direct effect on osteoclasts and their precursors. By interacting with specific receptors on the surface of these cells, CT causes a significant inhibition of the activity of osteoclasts and their ability to move to sites of resorption; in addition, it inhibits the transformation of preosteoclasts into mature osteoclasts and, as a result, significantly reduces the number of actively resorbing cells in the remodeling site. In addition, salmon CT is able to stimulate bone formation, and this effect is mediated by its effect on osteoblasts (Table 2). Receptors for CT are found in small quantities not only on osteoblastic cells, but also in the kidneys and central nervous system. Data have also been obtained on other effects of CT, including anti-inflammatory activity detected in fractures, a positive effect on the regeneration of bone tissue and cartilage, as well as a hypotensive effect. A special place is occupied by the analgesic effect of CT, since pain (especially in the spine) is a characteristic manifestation of AP and significantly affects the patient’s quality of life. The mechanism of the analgesic effect is carried out through several mechanisms: 1) increasing the level of endorphins in the blood; 2) effects on the metabolism of serotonin and monoamines in the central nervous system; 3) decreased sensitivity of nociceptive receptors to local algogenic factors (histamine, serotonin, prostaglandins, kinins, acetylcholine, etc.), suppression of the formation of mediators involved in pain transmission (neurotensin, somatostatin, etc.). Both parenteral and intranasal forms of CT have a pronounced analgesic effect [16]. Nasal CT has been shown to reduce pain in osteoporotic vertebral fractures. CT also reduces bone pain (metastatic tumors, osteoporosis and Paget's disease) and other types of pain, including headaches and post-operative pain. In addition, along with other calcium-regulating hormones, CT is involved in maintaining calcium homeostasis. The largest and longest-running study of salmon CT (Miacalcic) is the PROOF study (2000), which was conducted over 5 years at 47 centers in the USA and the UK. In the group of patients receiving Miacalcic at a daily dose of 200 IU, the incidence of new fractures decreased by 33%, and in the subgroup of women with initially existing clinically significant fractures of the vertebral bodies by 36% (Fig. 1). The PROOF study raised the question of the possible existence of a mechanism of action of salmon CT aimed at reducing the risk of bone fractures that is not directly related to an increase in BMD. The main premise for the creation of the “bone quality concept” was the observation that many drugs that moderately increase BMD cause a significant reduction in the risk of fractures and, on the contrary, others that lead to a pronounced increase in BMD do not affect the risk of fractures. To confirm the concept of improved bone quality as a result of treatment with Miacalc, a double-blind, placebo-controlled, randomized trial, QUEST, was conducted (from 1998 to 2001) among women with postmenopausal AP complicated by vertebral fractures [17]. To assess the effectiveness of treatment, a study of iliac bone biopsy samples, microcomputed tomography of biopsy samples and magnetic resonance imaging of bone tissue were carried out. The results of the study indicate an improvement in the quality of bone tissue during Miacalc therapy. Also, the QUEST study found a statistically significant increase in the number of osteoblasts per unit of bone surface during the treatment period, which may indicate stimulation of bone formation by Miacalcic. Treatment with Miacalcic, according to the results of the QUEST study, led to a decrease in the intensity of bone resorption by 26%. At the same time, the BMD of the lumbar vertebrae increased by only 0.8%. Histomorphometry showed no signs of impaired mineralization or the appearance of foci of coarse-fibrous, defective bone tissue during CT treatment of salmon. Most significantly, the results of two studies of salmon calcitonin - PROOF and QUEST - showed that Miacalcic at a dose of 200 units intranasally reduces the risk of vertebral fractures and improves bone quality to a greater extent than it increases BMD. Using magnetic resonance imaging in certain regions of the skeleton, a significant increase in the number of trabeculae was revealed by 1–9%, an increase in the ratio of bone volume to total volume by 2–10%, an increase in the thickness of trabeculae by 0.1–1.5%, a decrease in resorptive cavities in trabeculae by 3–14%, a decrease in relaxation time by 2.6–7.4%. In accordance with the conclusions of experts participating in the Proof program, it is recommended to prescribe an intranasal form of the myacalcic in a single daily dose of 200 IU continuously for 3-5 years. There is also the experience of cyclic use of the drug (alternation of 2-3 -month therapeutic courses with 2-3 -month breaks in treatment), although the effectiveness of the intermittent use of the drug still needs to be evaluated. Simultaneously with the myacalcic, calcium is prescribed (500-1000 mg/day) and, according to indications, vitamin D (200-400 IU/day). Miacalcic can be used to prevent progressive bone tissue vacuum in patients with osteopenia. In such cases, the regimes of the drug are the same as in the treatment of osteoporosis. The effectiveness of myacalcic in the treatment of acute pain in women with postmenopausal OP was confirmed in four blind placebo -controlled studies. In the first of them, the drug was prescribed intranasally at a dose of 200 IU/day. In the course of 4 weeks in patients with vertebral fractures. After 7 days, treatment with a myacalcic compared to the placebo led to a significant decrease in the severity of pain. The pain index in the main and control groups was 1.8 and 3.0, respectively, and after 28 days - 0.5 and 2.5 (Fig. 2). In another double blind study, the miacalcik nasal spray was used for 4 weeks [Grendale Ga, 1997]. After 1 week of treatment, the drug led to a significant decrease in pain and the need for NSAIDs; The achieved effect was preserved until the end of the study. In most patients, in 1 week, mobility completely restored. Throughout the study, the number of patients chained to bed in the placebo group was larger than in the Miacalcic group. In two other placebo -controlled studies, the myacalcic was used parenterally at a dose of 200 IU/day. . The pain index in patients with a spinal fracture decreased to 1.14 in the calcitonin group and to 2.0 in the placebo group (p <0.005). The functional activity of functional activity by the end of the study also decreased more in the main group. Domestic authors used the myacalcic intranasally according to the intermittent scheme for postmenopausal and senile OP (Table 3). A significant decrease in Ossalgia was noted not only during the treatment, but also in the break between them. In addition, a decrease in the Adenonurotic syndrome and general weakness was noted. The positive effect of the myacalcic in the treatment of fractures of the proximal femoral bone is noted in the works of Solod E.I. et al. The results of open controlled studies have shown that the analgesic effect of the myacalcic remains for a long time (6-12 months). The analgesic effect of the myacalcic in patients of the OP does not depend on the path of its administration, however, in a number of observations when using the nasal spray, the faster relief of the pain syndrome was revealed. The use of myacalcic also revealed its effectiveness in the treatment of steroid osteoporosis in patients with lung diseases (Fig. 3). With intranasal use of salmon calcitonin in patients with bronchial asthma who received prednisone for a long time, an increase in the spinal IPC was observed by 2.8% for a 2 -year observation period, while among patients treated only with calcium preparations, the MPC was reduced by 7, 7 8% . In patients with sarcoidosis, after 1 year of treatment, prednisolone was noted by a decrease in the MPC of the spine by 13.9%, while against the background of the appointment of calcitonin MPC increased by 0.2%. In an open placebo -controlled study in patients with bronchial asthma, it was found that in a group of the Miaakalcic treated the average growth of the MPC of the lumbar spine was 2.7, while in the group of patients receiving placebo, the indicators of the MPC decreased by 2.8 (in both of them in both Groups were additionally prescribed calcium at a daily dose of 1000 mg). Favorable effects in the prescription of myacalcic were noted in rheumatological patients with OP, which developed within the framework of systemic immunosphereal diseases, as well as with osteoarthritis and a number of endocrine diseases (hyperparathyroidism, thyrotoxicosis). Another important aspect of the effectiveness of the use of myacalcic was detected in the prevention of postoperative bone loss, especially in patients with fractures of the femoral neck. Early postoperative use of salmon calcitonin is of special clinical significance in older people with fractures, as the drug accelerates fractures, prevents the development of immobilization and regional osteoporosis, and also accelerates the mobilization of patients, while giving an additional analgesic effect. Miaakalcic therapy at a dose of 200 IU/day. Intranasally leads to a reliable (by 33%) reduction in the risk of new vertebral fractures, which were diagnosed on the basis of morphometric research of spondylograms. Most researchers note the high therapeutic potential of Miacalcic with minimal side effects. A distinctive characteristic of the drug CT Salmon is its safety and good tolerance. Of the side effects, it should be noted the transient redness of the face, as well as dyspepic phenomena (nausea, headache, extremely rare vomiting and stool disorder). With intramuscular or subcutaneous administration, hyperemia and soreness at the injection site can be noted, and with intranasal use - irritation of the nasal mucosa, sneezing and other manifestations of rhinitis. Thus, the myacalcic is a fairly effective remedy for the treatment of OP. At the same time, in people with pain, due to severe osteoporosis, this drug can be considered a means of the first line of treatment. Reducing the risk of repeated fractures when using myacalcic is achieved by stabilizing MPCT in the spine and trabecular areas of other bones. This is also facilitated by the restoration of the quality of bone tissue, determined by the architectonics of bone trabecul and the biochemical characteristics of the mineral and organic components of bone substance. In the treatment of OP, drugs of other classes are also used that inhibit bone resorption or activate its formation. Bisphosphonates (BF) - synthetic derivatives of phosphonic acids. The mechanism of their action on bone tissue is carried out through the metabolism and functional activity of osteoclasts. Bisphosphonates include: alendronate, zoledronic acid, rizendronate, ibandronate, as well as other drugs that are currently used less often (ethridnate, clodronate, pamipronate and tiluronate). The effectiveness of bisphosphonates is convincingly proven by a large number of clinical studies. In the multicenter (34 countries) study of Fosit (1996), Alendronate treatment led to a decrease in the vertebral fractures by 47%, hips by 51% and forearms by 48% [17]. A similar effect was given by Risendronate in the Vert (1999) study, which reduced the risk of fractures of the hip neck by 30% [18]. The main side effect of oral forms of BF is the damage to the gastrointestinal tract. Strontia Ranlat stimulates the synthesis of new bone tissue by replicating tensiles and suppresses resorption, reducing the differentiation of the tensiles to osteoclasts. The effectiveness of the strontium of the wound in the prevention of fractures was evaluated during two clinical studies. In the SOTI (2004) study, the drug reduced the risk of new vertebrates in patients with a history of fractures by 49% a year later from the start of treatment [19]. In the study by Tropos (2005), treatment led to a decrease in the risk of hip fractures by 36% [20]. Hormone replacement therapy (HRT). In recent decades, estrogens or their combinations with progestagen have found widespread use in the treatment of OP [21]. Clinical studies have shown that estrogens reduce the risk of fractures of the femoral neck and compression fractures in patients with a progressive course of postmenopausal OP. The main indication for the purpose of the HRT is the postmenopausal OP, accompanied by the severe course of menopause. Calcium and Vitamin D. In prospective control -fighting studies, it was shown that the isolated use of calcium salts irrelevantly increases the MPT, but reduces bone resorption. In the IR Reid Savavt. (1993) The study shows that in the placebo group the average value of bone mass loss throughout the skeleton was 1% per year, and in the group under study it was almost half as much [22]. The role of calcium salts in therapy and prevention of the senile OP is especially growing. In the study by R. Recker et al. (1994) The frequency of new vertebral fractures in older women decreased by 45% compared to the placebo group [23]. It should be emphasized that in complex therapy, the OP is important calcium, therefore its salts are prescribed along with anti -rezorbetic drugs as the basis of pathogenetic therapy.

Indications for use

Miacalcic injection solution and spray are indicated for use in:

deforming osteodystrophy (Paget's disease);
sensation of bone pain associated with osteopenia and/or osteolysis ;
postmenopausal osteoporosis (at early and late stages of development);
neurodystrophic pathologies (Sudek's atrophy, algoneurodystrophy) caused by various predisposing and etiological factors, including: painful post-traumatic osteoporosis , glenohumeral syndrome , reflex dystrophy, causalgic syndrome , neurotrophic drug disorders.

Additionally, the injection solution is used for:

primary senile osteoporosis in men and women;
secondary osteoporosis , including that developed due to prolonged immobilization and treatment with glucocorticoids ;
acute pancreatitis (as a means of additional therapy);
hypercalcemic crisis and hypercalcemia caused by the following painful conditions: osteolysis provoked by malignant tumors ( myeloma , carcinoma of the lungs, breast, kidneys); prolonged immobilization ; hyperparathyroidism ; intoxication (poisoning) with vitamin D ; (used for the relief of acute conditions and for long-term therapy of chronic pathologies, until the effect of specific treatment of the underlying disease manifests itself).

Nosological classification (ICD-10)

E21 Hyperparathyroidism and other disorders of the parathyroid gland
E67.3 Hypervitaminosis D
E83.5 Disorders of calcium metabolism
E83.5.0* Hypercalcemia
G56.4 Causalgia
K85 Acute pancreatitis
M62.3 Immobilization syndrome (paraplegic)
M81.0 Postmenopausal osteoporosis
M81.2 Osteoporosis due to immobility
M81.4 Drug-induced osteoporosis
M81.8.0* Senile osteoporosis
M81.9 Osteoporosis, unspecified
M88 Paget's disease (bone) [osteitis deformans]
M89.0 Algoneurodystrophy
M89.5 Osteolysis
M89.8 Other specified bone lesions
M89.9 Bone disease, unspecified
M90.8 Osteopathy in other diseases classified elsewhere
N95.1 Menopausal and menopausal conditions in women
T45.2 Poisoning by vitamins not elsewhere classified

Side effects

When using the injection solution and spray Miacalcic, undesirable side effects may occur such as: dizziness , nausea/vomiting, arthralgia , mild flushing of the facial skin with a feeling of warmth. Dizziness, nausea / vomiting and hot flashes were dose-dependent and were more often observed with intravenous administration of Miacalcic, compared with its subcutaneous or intramuscular use. During therapy using Miacalcic, chills and polyuria , which, as a rule, disappear on their own and only sometimes require a temporary reduction in the dosage of the drug.

Also, with varying frequency of manifestations, the use of Miacalcic can lead to the following negative phenomena.

Often:

headache;
arthralgia;
dizziness;
stomach ache;
taste disorders;
tides;
nausea;
increased fatigue ;
diarrhea.

Sometimes:

visual disturbances;
arterial hypertension;
swelling of the face;
vomit;
pain in muscles and bones;
influenza-like syndrome;
generalized and peripheral edema.

Rarely:

Side effects of the drug Miacalcic

Nausea, vomiting, dizziness, and slight flushing of the face may occur. These effects are dose dependent and are most often observed with IV administration compared to IM and SC administration. Rarely - polyuria, chills. These effects usually disappear on their own, and only in isolated cases may a temporary dose reduction be necessary. The following adverse reactions are distributed according to frequency of occurrence: very often (1/10), often (1/100, ≤1/10), infrequently (1/1000, ≤1/100), rarely (≥1/10,000, ≤ 1/1000), very rare (≤1/10,000), including isolated reports. From the immune system: rarely - hypersensitivity; very rarely - anaphylactic and anaphylactoid reactions, anaphylactic shock. From the side of the central nervous system: often - dizziness, headache, taste disturbance (dysgeusia). From the side of the organ of vision: infrequently - visual impairment. From the cardiovascular system: often - hot flashes; infrequently - hypertension. From the gastrointestinal tract: often - nausea, diarrhea, abdominal pain; infrequently - vomiting. On the skin: rarely - generalized skin rash. From the musculoskeletal system and connective tissue: often - arthralgia; infrequently - muscle and bone pain. From the urinary system: rarely - polyuria. General disorders and reactions at the injection site: often - fatigue; infrequently - flu-like symptoms, edema (facial, peripheral and generalized); rarely - reactions at the injection site, itching.

Instructions for use of Miacalcic (Method and dosage)

Miacalcic injection solution, instructions for use

Miacalcic in the form of an injection solution is intended for subcutaneous, intramuscular and intravenous administration.

For the treatment of osteoporosis, subcutaneous or intramuscular administration of the drug is indicated in a daily dosage of 50 IU or 100 IU every day or every 24 hours (depending on the severity of the disease). To prevent the progression of bone loss, it is recommended to prescribe vitamin D and calcium in adequate doses in parallel with Miacalcic.

For painful bone syndrome associated with osteopenia and/or osteolysis , daily administrations are prescribed in a daily dose of 100-200 IU. The drug can be administered by infusion (in saline solution), as well as by intramuscular or subcutaneous injections in a series of injections until satisfactory clinical efficacy is achieved. The dosage of Miacalcic should be adjusted taking into account the patient's response to therapy.

It may take several days analgesic effect to develop If long-term treatment is necessary, the initial daily dosage of the drug and/or the frequency of its use is usually reduced.

For Paget's disease, Miacalcic is administered intramuscularly and/or subcutaneously at a daily dosage of 100 IU, applied daily or every 24 hours. The minimum duration of therapy is 3 months. The dose of the drug is selected taking into account the patient's response to the treatment.

Emergency treatment of a hypercalcemic crisis is carried out in the form of infusion, which is most effective in relieving emergency and other severe painful conditions. In this case, the daily dose of Miacalcic is calculated per kilogram of the patient’s weight and is usually 5-10 IU/kg, dissolved in 500 ml of saline solution . The infusion is carried out over a minimum of 6 hours. Slow intravenous administration of Miacalcic is also allowed, dividing the daily dosage of the drug into 2-4 times.

Long-term treatment hypercalcemia is recommended to be carried out in the form of intramuscular or subcutaneous injections in a daily dosage of 5-10 IU/kg, used once or twice every 24 hours. The dosage regimen is adjusted based on the clinical dynamics of the patient’s condition and his biochemical parameters . If the required Miacalcic dose volume of 2 ml is exceeded, preference is given to intramuscular injections carried out in different places.

In the treatment of neurodystrophic pathologies, early diagnosis of the disease is extremely important. Treatment begins immediately after an accurate diagnosis. Miacalcic is prescribed in the form of intramuscular and/or subcutaneous injections in a daily dosage of 100 IU, administered over 2-4 weeks. Continuation of treatment is possible with the administration of the drug at 100 IU every 24 hours for up to 6 weeks (consistent with the dynamics of the patient’s painful condition).

Treatment of acute pancreatitis with the use of Miacalcic is carried out as part of a combinatorial conservative treatment. The drug is administered as an infusion at a dose of 300 IU dissolved in saline . Infusions are carried out over 24 hours for 6 days in a row.

Miacalcic spray, instructions for use

Miacalcic spray is intended for intranasal use (in the nasal cavity). It is recommended to administer the spray by alternating the nasal passages.

For the treatment of osteoporosis , a daily dose of Miacalcic is prescribed, amounting to 200 IU. To prevent the progression of bone loss, it is recommended to prescribe vitamin D and calcium in adequate doses in parallel with the spray. Treatment is carried out over a long period of time.

For painful bone syndrome associated with osteopenia and/or osteolysis , a spray is used in a daily dosage of 200-400 IU, administered daily. A dose of 200 IU can be used simultaneously. Higher dosages must be administered in several doses. The dose of Miacalcic spray should be adjusted according to the individual needs of the patient.

It may take several days analgesic effect to develop If long-term treatment is necessary, the initial daily dosage of the drug and/or the frequency of its use is usually reduced.

For Paget's disease, daily use of the spray is recommended at a daily dosage of 200 IU. Sometimes, at the beginning of therapy, a daily dose of 400 IU, administered in several doses, may be necessary. The minimum duration of treatment should be 3 months. The dosage is adjusted taking into account the personal needs of the patient.

Treatment with Miacalc for Paget's disease should be continued continuously for several months or even several years. When carrying out such therapy, a significant decrease in plasma alkaline phosphatase and renal excretion of hydroxyproline , sometimes to standard values. However, in some cases, an increase in these indicators was noted after their initial decrease. If such a clinical picture is detected, the doctor should consider the advisability of discontinuing treatment and its subsequent resumption.

Several months after completion of therapy, disorders of bone and tissue metabolism may occur again. In this case, a repeat course of treatment is required.

In the treatment of neurodystrophic pathologies, early diagnosis of the disease is extremely important. Treatment begins immediately after an accurate diagnosis. Miacalcic is prescribed in the form of a spray in a daily dose of 200 IU once daily for 2-4 weeks. Continuation of treatment is possible with the administration of the drug 200 IU every 24 hours for up to 6 weeks (consistent with the dynamics of the patient’s painful condition).

Experience with the use of Miacalcic injection solution and spray in pediatrics is quite limited, and therefore it is not possible to give recommendations for their use in this age group.

Significant experience with the use of both dosage forms of Miacalcic, used for the treatment of elderly patients, confirms the normal tolerability of the drugs by patients in this age group, as well as the absence of the need to adjust the dosage regimen. The same picture is observed in patients with / kidney pathologies , although targeted studies of the effect of Miacalcic on patients in these groups have not been conducted.

Device for administering nasal spray

The primary packaging of the spray used for further intranasal use is:

a bottle containing a solution of the drug in a volume sufficient for at least 14 injections;
a protective cap that protects the tip from contamination and the outlet from clogging;
a tip intended for insertion into the nasal passage;
a sprayer (piston), which is a moving part of the bottle used for the procedure of spraying the solution;
the outlet is a small hole in the center of the tip through which the solution is injected;
the tube is located inside the bottle and serves to supply the solution after pressing the sprayer;
a dose counter showing the doses used; a window on the sprayer (on a full bottle the window is completely red).

Preparing the nasal spray for use

Shaking the bottle with the drug is not allowed, as this may cause the formation of air bubbles in the solution, which will lead to incorrect dosing of the drug.

The dosage counter window for unused spray should be red.

When using the spray for the first time, remove the protective cap from the tip of the sprayer and, holding the bottle vertically, make three preliminary presses on the piston to remove air from the tube. This procedure is carried out once to bring the spray into working condition. When removing air from the tube, slight splashing of the solution itself is allowed, which is provided by the manufacturer and does not affect the further number of doses.

You should pay attention to the color change in the counter window after each subsequent press on the piston. After the third preventive press, a green color should appear in the window, indicating that the device is ready for further use.

Method of using nasal spray

To properly use Miacalcic nasal spray, the patient should tilt his head slightly forward and insert the tip of the spray into the nasal passage. Make sure that the tip of the nebulizer is positioned in line with the nasal passage to ensure even distribution of the drug.
Press the piston once.
Remove the tip from the nasal passage and take several active breaths through the nose to prevent the solution from leaking out.
You should not clear your nasal passage immediately after using the drug.
If the doctor prescribes 2 injections at a time, the second procedure is carried out in the other nasal passage.
After using the spray, carefully wipe the spray tip with a dry, clean cloth and put the protective cap on it.

Nasal spray dose recording

Before using the spray, as well as after its use, it is necessary to mark the number in the dosage counter window, which should increase by one value after each subsequent injection of one dose of the drug. A bottle of nasal spray includes 14 full doses, but taking into account the supply of solution provided by the manufacturer, it is possible to carry out 2 additional sprays.

The appearance of the number 16 in the dose window means the complete absence of solution in the bottle. A slight residue of the drug at the bottom of the bottle cannot be used.

Additional warnings

Do not disassemble the spray device or attempt to enlarge the tip opening using a needle or other sharp object. Such interference will lead to serious disruption of the operation of the spraying device. If you have any doubts about the correct operation of the device, you should consult with a specialist at the pharmacy where the spray was purchased.

To ensure accurate dosage measurements, the vial of the drug should be stored and transported in an upright position. Shaking the bottle is not allowed. Sudden temperature changes should be avoided. The used bottle can be stored at room temperature for a maximum of 4 weeks.

Overdose

Negative symptoms of overdose with parenteral administration of Miacalcic are manifested by hot flashes , nausea/vomiting and dizziness , which are dose-dependent. When using Miacalcic intranasally in the form of a spray, similar phenomena can be expected. However, there are reports of cases of using Miacalcic spray in single doses of up to 1600 IU and in daily doses of 800 IU, used for 3 days, which did not lead to any serious negative effects. Cases of overdose with Miacalcic spray are occasional. An overdose of salmon calcitonin may cause hypocalcemia , accompanied by muscle twitching and paresthesia .

salmon calcitonin overdose should be appropriate to the negative symptoms observed. In case of development of hypocalcemia, of calcium gluconate is indicated .

Composition and release form

Injection	1 ml
synthetic salmon calcitonin	100 ME
(1 IU corresponds to approximately 0.2 mcg of synthetic salmon calcitonin)
excipients: acetic acid; sodium acetate trihydrate; sodium chloride; water for injections

in ampoules of 1 ml; There are 5 ampoules in a cardboard pack.

Spray for nasal use, dosed	1 ml
synthetic salmon calcitonin	200 ME
excipients: benzalkonium chloride; sodium chloride; hydrochloric acid; purified water

in bottles with a sprayer; There are 1 or 2 bottles in a cardboard pack.

special instructions

A physician or nurse experienced in performing subcutaneous injections should instruct the patient in the proper technique for performing such procedures independently.

Miacalcic injection solution contains less than 23 mg sodium .

Before injecting Miacalcic, it is necessary to visually examine the condition of the solution and ampoule of the drug. It is allowed to use a colorless, transparent injection solution that does not contain foreign inclusions, enclosed in an intact ampoule. After a one-time use of Miacalcic, the remainder of the unused solution in the ampoule should be disposed of.

Before administering Miacalcic intramuscularly or subcutaneously, the ampoule with the injection solution should be warmed to room temperature.

With prolonged use of any of the dosage forms of the drug Miacalcic, the formation of antibodies to calcitonin , which, as a rule, did not affect the overall picture of the clinical effectiveness of the drug. The phenomenon of "addiction", mainly observed in patients with Paget's disease , using Miacalcic for a long period of time, is probably due to the saturation of drug binding sites, and not the release of antibodies to calcitonin . After a break in therapy, the effectiveness of Miacalcic is completely restored.

Treatment of Paget's disease , like other chronic pathologies that occur with increased bone turnover , should be long-term and take several months or even several years.

During Miacalc therapy, plasma alkaline phosphatase and renal excretion of hydroxyproline are significantly reduced or normalized. However, in some cases, an increase in these indicators was noted after their initial decrease. If such a clinical picture is identified, the doctor should consider the advisability of discontinuing treatment and its subsequent resumption, consistent with the clinical picture of the disease.

Several months after completion of therapy, disorders of bone and tissue metabolism may occur again. In this case, a repeat course of treatment is required.

Due to the peptide basis of salmon calcitonin , when using Miacalcic, there is a possibility of the formation of systemic allergic manifestations . There is information about the development of allergic reactions , including isolated cases of anaphylactic shock . If a patient is suspected of hypersensitivity to salmon calcitonin , skin tests using a sterile diluted solution of Miacalcic should be prescribed before starting therapy.

During pregnancy and lactation

In the course of experimental studies, teratogenic or embryotoxic effects of Miacalcic were noted, nor was its penetration through the placental barrier . However, there are no clinical data on the safety of using Miacalcic for the treatment of pregnant women. As a result, it is not recommended to prescribe any of the dosage forms of this drug during pregnancy .

salmon calcitonin passes into the milk of a nursing mother has not been established. In this regard, Miacalcic should not breastfeeding

Reviews of Miacalcic

On the Internet you can mainly find reviews about Miacalcic spray and much less often reviews about the injection solution of this drug. Quite a varied assessment by patients of the effects of Miacalcic does not make it possible to draw an unambiguous conclusion about the effectiveness and safety of its use. For some, this drug is completely suitable, for others, due to severe side effects ( nausea / vomiting , hot flashes , dizziness ), it only harms others.

Also, you may come across references to the ability of Miacalcic to cause cancer , although official confirmation of this phenomenon has not been provided. If it is necessary to use drugs like Miacalcic, the patient should listen to the opinion of a doctor whom he completely trusts or consult with several independent specialists.