Instruction for use: Miacalcic

Active substance Calcitonin

ATX Code H05BA01 Calcitonin

Pharmacological groups

Hormones of the thyroid and parathyroid glands, their analogs and antagonists (including antithyroid agents) / 67 /

Calcium-phosphorus metabolism regulator [Correctors of bone and cartilage tissue metabolism]

Nosological classification (ICD-10)

E21 Hyperparathyroidism and other disorders of the parathyroid [parathyroid] gland

Hyperparathyroidism

E67.3 Hypervitaminosis D

E83.5 Disorders of calcium metabolism

Loss of calcium in bones and teeth, Replenishment of a lack of calcium, Malabsorption of calcium, Violation of calcium metabolism in the body, Violation of the calcium-phosphorus balance, Disturbance of calcium metabolism, Impaired calcium absorption, Decreased calcium absorption, Replenishment of calcium deficiency

E83.5.0 * Hypercalcemia

Hypercalcemic crisis, Idiopathic hypercalcemia of newborns, Milk-alkaline syndrome

G56.4 Causalgia

Causalgic syndrome, Syndrome of causalgia

K85 Acute pancreatitis

Acute pancreatitis, Pancreatitis, Pancreatitis hemorrhagic, Pancreatitis acute, Sepsis pancreatogenic, Acute necrotic pancreatitis, Pancreatitis edematous

M62.3 Immobilization syndrome (paraplegic)

M81.0 Postmenopausal osteoporosis

Menopause osteoporosis, Osteoporosis in menopause, Osteoporosis in menopause, Osteoporosis in postmenopausal women, Osteoporosis in the postmenopausal period, Postmenopausal osteoporosis, Osteoporosis in postmenopausal women, Perimenopausal osteoporosis, Postmenopausal osteoporosis, Post-menopausal osteoporosis, Postmenopausal osteoporosis, Postmenopausal demineralization of bones, Osteoporosis with estrogen deficiency, Osteoporosis in postmenopausal women, Osteoporosis in postmenopausal women and after hysterectomy

M81.2 Osteoporosis caused by immobility

M81.4 Medicinal osteoporosis

Osteoporosis steroid, Steroid osteoporosis, Secondary osteoporosis due to the use of glucocorticoids

M81.8.0 * Osteoporosis senile

Osteoporosis senile, Senile osteoporosis in men, Older osteoporosis, Age-related osteoporosis, Senile Osteoporosis, Osteoporotic fracture in elderly patients

M81.9 Other specified osteoporosis

Osteoporosis due to androgen deficiency, Primary osteoporosis, Osteoporosis in men, Parathyroid osteoporosis, Primary osteoporosis, Post-traumatic osteoporosis, Loss of calcium in bones and teeth, Presennial osteoporosis, Systemic osteoporosis

M88 Paget's disease (bones) [deforming osteitis]

Paget's disease is bone, Paget's disease, Deforming osteodystrophy, Paget's disease, Deforming osteitis, Deforming Osteoporosis, Ostoz deforming, Osteitis deforming, Osteitis with articular manifestations

M89.0 Algoneurodroystrophy

Zudeck's atrophy, Zudeck's Syndrome, Shoulder-Arm Syndrome, Steinbroke Syndrome, Shoulder-Brush Syndrome, Brachialgia syndrome, Zudeck's posttraumatic reflex atrophy, Reflex sympathetic dystrophy

M89.5 Osteolysis

Acrosteolysis, Piknodizostoz, Osteolytic damage to bones, Spontaneous resorption of bones

M89.8 Other specified disorders of bones

Pain in the bones, Painful conditions of the musculoskeletal system

M89.9 Disease of bone, unspecified

Local osteopathy, Disturbance of bone mineralization processes, Osteopenia, Pain syndrome in acute inflammatory diseases of the musculoskeletal system, Pain syndrome in chronic inflammatory diseases of the musculoskeletal system, Pain in the musculoskeletal system, Infection of bones, Ossalgia, Pain in chronic degenerative bone diseases

M90.8 Osteopathy in other diseases classified elsewhere

Osteopathy, Local Osteopathy, Osteopenia, Nephrogenic osteopathy

N95.1 menopausal and menopausal status of women

Atrophy of the mucosa of the lower genital tract, caused by estrogen deficiency; Vaginal dryness; Autonomic dysfunction in women; gipoestrogeniya state; Deficiency of estrogen in menopausal women; Degenerative changes of the mucous membrane in the menopause; Natural menopause; an intact uterus; climacteric; Menopause women; Menopause in women; menopausal depression; Climacteric ovarian dysfunction; Menopause; Climacteric neurosis; Menopause; Menopausal symptoms complicated psychovegetative; Climacteric syndrome; Climacteric vegetative disorders; Climacteric psychosomatic disorder; menopausal disorders; Menopausal disorders in women; menopausal condition; Climacteric vascular disorders; Menopause; Menopausal vasomotor symptoms; menopausal period; Lack of estrogen; Feeling the heat; Pathological menopause; perimenopause; menopause; postmenopausal; Premature menopause; premenopauznom period; tides; hot flashes; flushing in the Meno and postmenopausal; Hot flashes / hot flashes in menopause; Heart attack during menopause; Early menopause in women; Disorders of menopause; climacteric syndrome; Vascular complications of menopause; Physiological menopause; Estrogendefitsitnye state; premature Menopause

T45.2 Poisoning with vitamins not elsewhere classified

Vitamin D poisoning, Overdose of pyridoxine

Composition and form of production

Solution for injection 1 ml

Synthetic salmon calcitonin 100 ME

(1 ME corresponds to about 0.2 μg of synthetic salmon calcitonin)

Auxiliary substances: acetic acid; Sodium acetate trihydrate; sodium chloride; water for injections

In ampoules of 1 ml; In a pack of cardboard 5 ampoules.

Spray for nasal application dosed 1 ml

Synthetic salmon calcitonin 200 ME

Auxiliary substances: benzalkonium chloride; sodium chloride; Hydrochloric acid; purified water

In vials with a nebulizer; In a pack of cardboard 1 or 2 bottles.

Description of dosage form

Solution for injection - a clear, colorless solution.

Spray nasal is a clear, colorless, odorless solution.

pharmachologic effect

Pharmacological action - inhibiting bone resorption, hypocalcemic.

Pharmacodynamics

The hormone produced by C-cells of the thyroid gland is an antagonist of parathyroid hormone and together with it participates in the regulation of calcium metabolism in the body.

The structure of all calcitonins is represented by one chain of 32 amino acids and a ring of 7 amino acid residues at the N-terminal, the sequence of which is not the same for different species. Since salmon calcitonin has a higher affinity for receptors (compared to mammalian calcitonins), its effect is expressed to the greatest extent both in strength and in duration.

By suppressing the activity of osteoclasts due to action on specific receptors, salmon calcitonin significantly reduces the rate of bone tissue exchange to normal levels in conditions with an increased rate of resorption, for example, in osteoporosis. Both in animals and in humans it has been shown that Miacalcic® has analgesic activity in bone pain, which is apparently due to direct effects on the central nervous system.

Already after a single application of Miacalcic® in the form of injectable solution or nasal spray, a clinically significant biological response is observed in man, which is manifested by increased urinary excretion of calcium, phosphorus and sodium (by reducing their tubular reabsorption) and decreased hydroxyproline excretion.

Prolonged parenteral or intranasal administration of Miacalcic® leads to a significant reduction in the level of biochemical markers of bone metabolism, such as pyridinoline, serum C-telopeptides (sCTX) and bone isoenzymes of AP.

Calcitonin in parenteral administration reduces gastric and exocrine pancreatic secretion. These properties of the drug Miacalcic® determine its effectiveness in the treatment of acute pancreatitis.

The use of Miacalcic® nasal spray results in a statistically significant (1-2% increase) in bone mineral density in the lumbar vertebrae, which is already determined in the first year of treatment and persists up to 5 years. The preparation Miacalcic® ensures the maintenance of mineral density in the femur.

The use of Miacalcic® nasal spray at a dose of 200 IU / day leads to a statistically and clinically significant decrease (by 36%) of the risk of developing new vertebral fractures in the group of patients who received Miacalcic® (in combination with vitamin D and calcium preparations), compared to With a group of patients who received a placebo (in combination with the same drugs). In addition, in the group of patients treated with Miacalcic® (in combination with vitamin D and calcium preparations), a 35% decrease in the incidence of multiple vertebral fractures was noted compared to the placebo group (in combination with the same drugs). Calcitonin reduces gastric and exocrine pancreatic secretion.

Pharmacokinetics

Bioavailability of calcitonin salmon with both intramuscular and subcutaneous injection is about 70%, and with intranasal application - 3-5% in relation to the bioavailability of the drug used parenterally. Cmax of the drug in plasma is achieved within 1 h, and with p / to administration - for about 23 minutes. The drug Miacalcic® is quickly absorbed through the nasal mucosa and its Cmax in plasma is reached during the first hour (on average, about 10 min).

The apparent VSS is 0.15-0.3 l / kg. Binding to plasma proteins - 30-40%. Up to 95% of calcitonin and its metabolites are excreted in urine, with only 2% in unchanged form. T1 / 2 of the drug is about 1 hour with an IM injection; 1-1.5 h - with subcutaneous injection and about 20 min - with intranasal.

With repeated prescriptions of the drug intranasal cumulation was not noted. When the drug was used in doses exceeding the recommended levels, its concentrations in the blood were higher (which was confirmed by an increase in AUC values), but the relative bioavailability did not increase.

Determining the concentration of salmon calcitonin in plasma, as well as the concentrations of other polypeptide hormones, is of little value, since the therapeutic effectiveness of the drug can not be predicted from the concentration level. Thus, the activity of Miacalcic® should be evaluated by clinical efficacy.

Salmon calcitonin does not penetrate the human placental barrier.

Indication

Common for both dosage forms

Bone pain associated with osteolysis and / or osteopenia;

Paget disease (deforming osteitis);

Neurodystrophic diseases (synonyms - algoneurodystrophy, Zudeck atrophy), caused by various etiological and predisposing factors, such as posttraumatic painful osteoporosis, reflex degeneration, humerus syndrome, causalgia, drug neurotrophic disorders;

Postmenopausal osteoporosis (both early and late stages).

Additionally for Miacalcic® for parenteral administration

Primary osteoporosis - senile osteoporosis in women and men;

Secondary osteoporosis, in particular caused by therapy with glucocorticoids or immobilization.

Hypercalcemia and hypercalcaemic crisis, caused by the following factors;

Osteolysis caused by malignant tumors (carcinoma of the breast, lungs, kidneys, myeloma, etc.);

Hyperparathyroidism;

Immobilization;

Intoxication with vitamin D;

Relief of emergency conditions and long-term treatment of chronic hypercalcemia - until the effect of specific therapy of the underlying disease appears;

Acute pancreatitis (as part of combination therapy).

Contraindications

Hypersensitivity to synthetic salmon calcitonin or any other component of the drug.

pregnancy and lactation

In experimental studies, the drug Miacalcic® had no embryotoxic and teratogenic effects and did not penetrate the placental barrier.

However, there are no clinical data on the safety of Miacalcic® during pregnancy. In this regard, the drug should not be used in women during pregnancy.

It is not known whether salmon calcitonin penetrates breast milk in humans, so it is recommended that breastfeeding be avoided during the period of drug therapy.

Side effects

Common for both dosage forms

There have been reports of such undesirable effects as nausea, vomiting, dizziness, minor flushes of blood to the face, accompanied by a feeling of warmth, arthralgia. Nausea, vomiting, dizziness and hot flashes depend on the dose and are more likely to occur with intravenous than with intramuscular or subcutaneous injection. Against the backdrop of the use of Miacalcic®, the development of polyuria and chills is possible, which usually disappear on their own, and only in some cases requires a temporary reduction in the dose of the drug. The incidence of adverse events, possibly associated with the use of the drug, is estimated as follows: very often (≥1 / 10); Often (≥1 / 100, <1/10); Sometimes (≥1 / 1000, <1/100); Rarely (≥1 / 10000, <1/1000), including individual messages.

From the immune system: rarely - hypersensitivity; Very rarely - anaphylactic or anaphylactoid reactions, anaphylactic shock.

From the nervous system: often - headache, dizziness.

From the senses: often - taste disorders; Sometimes - visual disturbances.

From the cardiovascular system: often - hot flashes; Sometimes - arterial hypertension.

From the digestive tract: often - nausea, abdominal pain, diarrhea; Sometimes - vomiting.

From the skin and subcutaneous tissue: rarely - generalized rash.

From the musculoskeletal system and connective tissue: often - arthralgia; Sometimes - pain in bones and muscles

From the urinary system: rarely - polyuria.

On the part of the body as a whole and local reactions: often - increased fatigue; Sometimes - the flu-like syndrome, facial swelling, peripheral and generalized edema; Rarely - chills, reactions at the injection site, itching.

Additionally for Miacalcic® nasal preparation

On the part of the respiratory tract: very often - tenderness in the nasal cavity, stagnant phenomena, edema of the nasal mucosa, sneezing, rhinitis, dryness in the nasal cavity, allergic rhinitis, erythema of the nasal mucosa, irritation, unpleasant odor, excoriation in the nasal cavity; Often - nosebleeds, sinusitis, ulcerative rhinitis, pharyngitis; Sometimes - cough.

Interaction

When calcitonin is used together with lithium preparations, a decrease in the plasma concentration of lithium is possible. Thus, with the simultaneous administration of Miacalcic® and lithium preparations, it may be necessary to adjust the dose of the latter.

Dosing and Administration

P / to, in / m (intramuscularly), intravenously (intravenously).

Osteoporosis. The drug is given SC or IM in a daily dose of 50 or 100 IU daily or every other day (depending on the severity of the disease). In order to prevent progressive loss of bone mass, the administration of adequate doses of calcium and vitamin D is recommended simultaneously with the use of Miacalcic®.

Bone pain associated with osteolysis and / or osteopenia. The daily dose is 100-200 IU daily. The drug is administered IV, dropwise (in physiological saline) or SC or IM in several administrations - until a satisfactory clinical effect is achieved. The dose should be adjusted taking into account the patient's response to treatment.

To achieve a complete analgesic effect may take several days. In long-term therapy, the initial daily dose is usually reduced and / or the interval between administrations is increased.

Paget's disease. P / to or in / m in a daily dose of 100 IU daily or every other day. The duration of treatment is at least 3 months; If necessary, it can be more. The dose should be adjusted taking into account the patient's response to treatment.

Hyperkalciemia. Emergency treatment of hypercalcemic crisis. Since IV infusion is the most effective way of administration, it should be given preference for treatment of urgent and other severe conditions.

Miacalcic® is injected intravenously into the drip for a minimum of 6 hours, at a daily dose of 5-10 IU / kg in 500 ml of saline. It is also possible in / in the jet slow injection, in which the daily dose should be divided into 2-4 injections during the day.

Long-term treatment for chronic hypercalcemia. Daily sc or to / m in a daily dose of 5-10 IU / kg once or in 2 injections. The dosage regimen should be adjusted taking into account the dynamics of the patient's clinical state and biochemical parameters. If the volume of the required dose of Miacalcic® is more than 2 ml, then I / m injections are preferable, which should be carried out in different places.

Neurodystrophic diseases. It is extremely important to make an early diagnosis. Treatment should be started immediately after confirmation of the diagnosis. P / to or in / m in a daily dose of 100 IU for 2-4 weeks. It is possible to continue treatment with the introduction of 100 IU every other day for up to 6 weeks, depending on the dynamics of the patient's condition.

Acute pancreatitis. Miacalcic ® is used as a part of combined conservative treatment. Introduce IV drip in a dose of 300 IU (in saline) for 24 hours to 6 consecutive days.

Intranasally. The introduction of the Niacal Spray Miacalcic® is recommended to alternate between one and the other nasal passage.

For the treatment of osteoporosis, the recommended dose is 200 IU / day. In order to prevent progressive loss of bone mass at the same time with the use of Miacalcic® in the form of a nasal spray, the administration of adequate doses of calcium and vitamin D is recommended. Treatment should be carried out for a long time.

Bone pain associated with osteolysis and / or osteopenia. The daily dose is 200-400 IU daily. A daily dose of 200 ME can be administered in 1 time. Higher doses should be divided into several injections. The dose should be adjusted to the individual needs of the patient.

To achieve a complete analgesic effect may take several days. In long-term therapy, the initial daily dose is usually reduced and / or the interval between administrations is increased.

Paget's disease. The drug is prescribed daily in a daily dose of 200 ME. In some cases, a dose of 400 IU / day may be required at the beginning of treatment, administered in several administrations. The duration of treatment is at least 3 months; If necessary, it can be more. The dose should be adjusted to the individual needs of the patient.

Note. With Paget's disease, the duration of treatment with Miacalcic® should be between a few months and several years. Against the backdrop of treatment, there is a significant decrease in the concentration of AP in the blood and excretion of hydroxyproline in the urine, sometimes to normal values. However, in some cases, after the initial decline, the values of these indicators may again rise. In these cases, the doctor, guided by the clinical picture, must decide whether treatment should be revoked and when it can be resumed.

One or several months after discontinuation of treatment, bone metabolism disorders may occur again; In this case a new course will be required.

Neurodystrophic diseases. It is extremely important to make an early diagnosis. Treatment should be started immediately after confirmation of the diagnosis. Assign 200 IU / day (in one administration) daily for 2-4 weeks. Additional administration of 200 IU every other day for up to 6 weeks is possible, depending on the dynamics of the patient's condition.

Use in children. The experience of using Miacalcic® solution for parenteral administration and nasal spray in children is limited, so it is not possible to give recommendations for this age group.

Use in elderly patients and individual patient groups. The extensive experience with Miacalcic® solution for parenteral administration and nasal spray in elderly patients suggests that there was no impairment of drug tolerance in this age group or the need to change the dosage regimen. The same applies to patients with decreased renal or hepatic function, although studies specifically for these groups of patients have not been conducted.

Nasal spray device and instructions for its use

Nasal Spray Device

1. Protective cap - protects the tip from the contamination (nozzle) and from the clogging - the outlet. After the drug is introduced, it is necessary to wear a protective cap.

2. Outlet - a small hole through which the drug solution is sprayed.

3. Tip - device (tube), which is inserted into the nasal passage.

4. Piston - part of the vial, pressing which activates the spray device.

5. Dose counter - a window that shows the dose. On still unused spray the window is red. When the use of the drug begins, other colors and numbers will be displayed in the window (for more details, see below).

6. Tube - the tube located inside the vial serves to feed the drug after pressing the pump.

7. Bottle - contains a medicinal preparation in the form of a solution in an amount sufficient for at least 14 injections.

The procedure for preparing nasal spray for use

Never shake the bottle; This can lead to the formation of air bubbles inside the vial, which will lead to incorrect dosing of the drug.

In the unused nasal spray, the dose counter is red. First remove the protective cap.

At the first application, hold the device with one or two hands strictly vertically, push the piston 3 times, which will allow air to escape from the tube. This should be done only once to bring the device into working order. Do not worry if a small amount of solution splashes together with the air (this is provided and does not affect the subsequent number of doses).

It is necessary to pay attention, that after each consecutive pressing on the piston, the color of the window of the counter of doses will vary.

After the third push, the window should turn green, which means the device is ready for use.

Thus, the nasal spray is ready for use.

The procedure for using a nasal spray

Slightly tilt the head forward and insert the tip into the nasal passage. Make sure that the tip is aligned with the nasal passage, which will ensure a more even distribution of the solution.

Press the piston 1 time.

Remove the tip from the nose and take a few vigorous breaths to prevent the drug from escaping.

Do not clean the nose immediately after applying the drug.

If the doctor has prescribed 2 injections at a time, then the second injection should be done in the other nasal passage.

Gently wipe the tip with a clean dry cloth. Put the protective cap on the tip.

Checking the dose count

Before and after using the spray, it is necessary to check the number in the dose counter window. After each use of the nasal spray, the number in the window will change. If a single dose is administered at a time, the previous value is increased by 1. The nasal spray contains 14 complete doses. Since the remainder of the solution is always provided in the vial, it is possible to obtain 2 additional doses.

When the number 16 appears in the window, it will mean that the drug has ended.

At the bottom of the vial, you can see a very small residual solution; It is not usable, it is provided.

Additional warnings

Never try to enlarge the nozzle opening with a needle or other sharp objects. This will lead to a complete malfunction of the device. Do not disassemble the pump. If there is any doubt about the operation of the device, you should consult the place where you purchased the drug. To ensure proper metering of doses, store and transfer the bottle in an upright position. Do not shake the bottle. Avoid sudden temperature changes. The vial should be stored at room temperature. It is suitable for a maximum of 4 weeks

Overdose

Symptoms: with parenteral use of the drug Miacalcic®, nausea, vomiting, hot flashes and dizziness are dose-dependent. Therefore, with an overdose of Miacalcic®, applied intranasally, we can expect similar phenomena. However, there are reports of cases when the Miacalcic® preparation in the form of a nasal spray was applied at a dose of up to 1600 IU once and at a dose of 800 IU per day for 3 days, with no serious adverse events noted. There are reports of individual cases of overdose. With an overdose, it is possible to develop hypocalcemia with symptoms such as paresthesia, muscle twitching.

Treatment: symptomatic; With the development of hypocalcemia - the appointment of calcium gluconate.

special instructions

A doctor or nurse should instruct the patients in detail who independently make themselves hypodermic injections of the drug.

Before applying Miacalcic®, you should visually check the condition of the ampoule and solution. The ampoule of the preparation should not be damaged, the solution should be transparent, colorless and without foreign inclusions. After a single application of Miacalcic®, the unused solution of the drug remaining in the ampoule should be disposed of. Before subcutaneous or intramuscular injection, the solution of Miacalcic® should be heated to room temperature. With prolonged use of the drug Miacalcic ® in patients can form antibodies to calcitonin; However, this phenomenon usually does not affect clinical efficacy. The phenomenon of "slippage", observed mainly in patients with Paget's disease, receiving the preparation Miacalcic® for a long time, is probably due to saturation of binding sites, rather than the formation of antibodies. After a break in treatment, the therapeutic effect of Miacalcic® is restored. In Paget's disease, as well as in other chronic diseases with an increased level of bone turnover, the duration of treatment with Miacalcic® should be from several months to several years. Against the background of treatment, the concentration of alkaline phosphor in the blood and the excretion of hydroxyproline in the urine are reduced, and often normalized. However, it should be borne in mind that in some cases, after the initial decline, the values of these indicators may again rise. In these cases, when deciding whether to cancel the treatment or the time of its resumption, the doctor should be guided by the clinical picture. One or several months after discontinuation of treatment, bone metabolism disorders may occur again, in which case a new course of treatment with Miacalcic® will be required.

Since salmon calcitonin is a peptide, there is a possibility of systemic allergic reactions. There have been reports of allergic reactions, including isolated cases of anaphylactic shock that occurred in patients receiving Miacalcic®. If susceptibility to a patient's sensitivity to salmon calcitonin is suspected, skin tests should be performed prior to treatment, using a diluted sterile solution of Miacalcic®.

The drug Miacalcic®, solution for injection, practically does not contain sodium (less than 23 mg).

Influence on the ability to drive vehicles and work with mechanisms. The effect of Miacalcic® on the ability to drive vehicles and work with mechanisms has not been studied. Some of the side effects of the drug, such as dizziness and visual disturbances, can adversely affect the ability to drive and perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

Note. With prolonged therapy, the formation of antibodies to calcitonin is possible, however, this is usually not affected by clinical efficacy. The phenomenon of addiction, which is observed mainly in patients with Paget's disease receiving long-term therapy, may be the result of saturation of binding sites and obviously has nothing to do with the formation of antibodies. The therapeutic effect of Miacalcic® is restored after a break in treatment.

Terms of leave from pharmacies

On prescription.

Storage conditions

At a temperature of 2-8 ° C.

Keep out of the reach of children.

Shelf life

Injection for 100 IU / ml - 5 years.

Spray nasal dosed 200 IU / dose - 3 years.

Do not use after the expiry date printed on the package.