Expiration date: 10/2025

The composition and form of issue:

Solution for injection. 1 ml contains:

synthetic calcitonin salmon 100 ME

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

excipients: acetic acid sodium acetate trihydrate sodium chloride water for injections 

in 1 ml ampoules in cartons of 5 ampoules.

Spray nasal dose of 1 ml:

synthetic calcitonin salmon 200 ME

excipients: benzalkonium chloride sodium chloride hydrochloric acid purified water 

in bottles with a spray in the stack cartons 1 or 2 bottles.

Description pharmaceutical form:

Solution for injection clear, colourless solution.

Nasal spray — a clear, colorless solution odorless.

Pharmacokinetics:

The bioavailability of calcitonin salmon as intramuscular and subcutaneous injection is about 70%, and in intra application — 3-5% relative to the bioavailability of the drug is used parenterally. Cmax of the drug in plasma achieved within 1 h, and when s/to the introduction — for about 23 min. the Drug Miacalcic is absorbed rapidly through the mucous membranes of the nose and its Cmax in plasma achieved within the first hour (only 10 min).

The apparent VSS is 0.15–0.3 l/kg plasma protein Binding is 30-40%. Up to 95% of calcitonin and its metabolites excreted in the urine, and only 2% in an unmodified form. T1/2 of the drug is about 1 h when the/m introduction 1-1,5 h when administered subcutaneously, and for about 20 minutes, with intra.

With repeated prescriptions indanazoline cumulation is not observed. In applying the drug in doses exceeding recommended, its concentration in the blood was higher (as evidenced by increase in AUC values), but the relative bioavailability was not increased.

Determination of the concentration of salmon calcitonin in the plasma, and the concentrations of other polypeptide hormones, is of little value, because the concentrations cannot be predicted therapeutic efficacy of the drug. Thus, the activity of the drug Miacalcin should be evaluated on clinical performance indicators.

Salmon calcitonin does not cross the placental barrier in humans.

Description pharmacological action:

A hormone produced by C cells of the thyroid gland, is an antagonist of parathyroid hormone and, together with him involved in the regulation of calcium metabolism in the body.

The structure of all calcitonin represented by a single chain of 32 amino acids and a ring of 7 amino acid residues at the N-Terminus, the sequence of which varies among different species. Since calcitonin salmon has a higher affinity to receptors (compared to calcitonine mammals), its effect was greatest both in force and duration.

Inhibiting the activity of osteoclasts by acting on specific receptors, salmon calcitonin significantly reduces the speed of bone to normal levels in States with high rate of resorption, e.g., osteoporosis. In both animals and humans have shown that the drug Miacalcin has analgesic activity for pain of bone origin, which appears to be due to direct effects on the Central nervous system.

Even after a single application of the drug Miacalcin in the form of solution for injection or nasal spray a person says clinically significant biological response, which is manifested by increased urinary excretion of calcium, phosphorus and sodium (by reducing their tubular reabsorption) and reduction of urinary excretion of hydroxyproline.

Long-term parenteral or intranasal use of the drug Miacalcin leads to a significant decrease in the level of biochemical markers of bone metabolism, such as pyridinoline, whey-telopeptide (sCTX) and skeletal isoenzymes of alkaline phosphatase.

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

The use of the drug Miacalcic nasal spray results in statistically significant increase (1-2%) bone mineral density in the lumbar vertebrae, which is determined in the first year of treatment and persisted up to 5 years. The drug Miacalcin maintains the mineral density in the femur.

The use of the drug Miacalcin nasal spray at a dose of 200 IU/day leads to a statistically and clinically significant reduction (36%) risk of developing new vertebral fractures in the group of patients receiving the drug Miacalcin (in combination therapy with vitamin D and calcium), compared to patients on placebo (in combination with the same drugs). In addition, in the group of patients treated with the drug Miacalcin (in combination therapy with vitamin D and calcium), compared to patients on placebo (in combination with the same drugs) marked a decline of 35% in the frequency of multiple vertebral fractures. Calcitonin reduces gastric and exocrine pancreatic secretion.

Indications:

For both dosage forms

• bone pain associated with osteolysis and/or osteopenia
  
• Paget's disease (osteitis deformans)
  
• neurodystrophic disorders (synonymous — algoneurodystrophy, atrophy sodeca) caused by various etiological and predisposing factors such as post-traumatic painful osteoporosis, reflex dystrophy, frozen shoulder syndrome, causalgia, drug-derived neurotrophic violations
  
• postmenopausal osteoporosis (both early and late stage).
  

Additionally, the drug for Miacalcin parenteral administration

• primary osteoporosis senile osteoporosis in women and men
  
• secondary osteoporosis, in particular caused by glucocorticoid therapy or immobilization.
  
• hypercalcemia and hypercalcemic crisis due to the following factors
  
• osteolysis caused by malignant tumors (carcinoma of the breast, lung, kidney, multiple myeloma, etc.)
  
• hyperparathyroidism
  
• immobilization
  
• intoxication with vitamin D
  
• relief emergency and long-term treatment of chronic hypercalcemia — as long as no manifest effect specific therapy of the underlying disease
  
• acute pancreatitis (in a combination therapy).
  

Contraindications:

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

Application of pregnancy and breast-feeding:

In experimental studies the drug Miacalcin did not render embryotoxic and teratogenic effects and did not penetrate through the placental barrier.

However, clinical data on the safety of the drug Miacalcin during pregnancy are not available. In this regard, the drug should not be used in women during pregnancy.

Unknown, do penetrates salmon calcitonin in breast milk in humans, so the period of drug therapy is recommended to abandon breastfeeding.

Side effects:

For both dosage forms

It was reported such unwanted effects as nausea, vomiting, dizziness, slight rush of blood to the face accompanied by feeling of warmth, arthralgia. Nausea, vomiting, dizziness and hot flashes are dose dependent and occur more frequently in the intravenous than by intramuscular or subcutaneous injection. On the background of the drug Miacalcin may develop polyuria and chills, which usually disappear on their own, and only in some cases require temporary reduction of the dose. The incidence of adverse events possibly related to use of the drug, is evaluated as follows: very common (&ge1/10) frequently (&GE. 1/100, <1/10), sometimes (&ge1/1000, <1/100) rare (&ge1/10000, <1/1000), including individual messages.

The immune system: rarely — hypersensitivity very rare — anaphylactic or anaphylactoid reactions, anaphylactic shock.

From the nervous system: often — headache, dizziness.

From the sensory organs: often — violation of taste and sometimes visual disturbances.

Of the cardiovascular system: often- hot flashes sometimes — arterial hypertension.

From the digestive tract: often — nausea, abdominal pain, diarrhea and sometimes vomiting.

The skin and subcutaneous tissue: rare — generalized rash.

On the part of the musculoskeletal system and connective tissue: often — arthralgia and sometimes pain in bones and muscles

From the urinary system: rarely — polyuria.

From the body in General and local reactions: often — fatigue and sometimes flu-like symptoms, swelling of the face, peripheral and generalized edema rarely vomiting, reactions at the injection site, itching.

Additionally, the drug Miacalcin nasal

From the respiratory tract: very often — pain in the nasal cavity, congestion, swelling of nasal mucosa, sneezing, rhinitis, dry in the nasal cavity, allergic rhinitis, erythema of the nasal mucosa, irritation, unpleasant odor, the formation of excoriation in the nasal cavity often — nasal bleeding, sinusitis, ulcerative rhinitis, pharyngitis, and sometimes a cough.

Drug interactions:

When using calcitonin along with the drug lithium may reduce the plasma concentrations of lithium. Thus, while the appointment of the drug miacalcin and drugs lithium may need a dose adjustment of the latter.

Method of application and dose:

P/to, in/m, in/in.

Osteoporosis. The drug is injected p/to or/m in a daily dose of 50 or 100 ME every day or two (depending on the severity of the disease). To prevent progressive bone loss from use of the drug Miacalcin recommended the appointment of adequate doses of calcium and vitamin D.

Bone pain associated with osteolysis and/or osteopenia. The daily dose is 100-200 ME daily. The drug is administered in/in, drip (saline) or p/or/m in a few introductions to achieve a satisfactory clinical effect. The dose should be corrected taking into account the patient's response to treatment.

To achieve the full analgesic effect may take several days. When conducting long-term therapy, the initial daily dose usually reduce and/or increase the interval between wvedeniami.

Paget's Disease. P/to or/m in a daily dose of 100 ME 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 based on patient response to treatment.

Gipercalziemia. Emergency treatment of hypercalcemic crisis. As in/in infusion is the most effective way of administration, it and preference should be given to emergency treatment and other serious conditions.

The drug Miacalcic injected in/in drip for at least 6 h, in a daily dose of 5-10 IU/kg in 500 ml saline. It is also possible/jet slow introduction in which the daily dose should be divided into 2-4 during the day.

Long-term treatment in chronic hypercalcemia. Daily p/to or/m in a daily dose of 5-10 IU/kg once or in 2 introduction. The dosage regimen may have to be corrected taking into account the dynamics of the patient's clinical condition and biochemical parameters. If the amount of the required dose of the drug Miacalcin exceeds 2 ml, preferably in the/m injection, which should be carried out in different places.

Neurodystrophic diseases. Extremely important early diagnosis. Treatment should begin immediately after confirmation of the diagnosis. P/to or/m in a daily dose of 100 ME in the next 2-4 weeks. It is possible to continue treatment with the introduction of 100 ME a day for up to 6 weeks depending on the dynamics of the patient.

Acute pancreatitis. The drug Miacalcin is used in the combined conservative treatment. Give/drip in the dose of 300 ME (in saline) for 24 h to 6 days in a row.

The intranasal route. The introduction of the nasal spray Miacalcin recommended alternately in one and then in the other nostril.

For the treatment of osteoporosis the recommended dose is 200 IU/day. To prevent progressive bone loss from use of the drug Miacalcin the nasal spray is recommended the appointment of adequate doses of calcium and vitamin D. Treatment should be for a long time.

Bone pain associated with osteolysis and/or osteopenia. The daily dose is 200-400 ME daily. Daily dose, component 200 ME, may be introduced for the 1st time. Higher doses should be divided into several injections. The dose should be adjusted to the individual needs of the patient.

To achieve the full analgesic effect may take several days. When conducting long-term therapy, the initial daily dose usually reduce and/or increase the interval between wvedeniami.

Paget's Disease. The drug is prescribed in daily daily dose of 200 ME. In some cases, early treatment may require a dose of 400 IU/day designated in several injections. 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. Paget's disease of duration of treatment Miacalcin should be from several months to several years. On the background of treatment noted a significant decrease in the concentration of alkaline phosphatase in the blood and in the excretion of hydroxyproline with urine, sometimes to normal values. However, in some cases, after the initial decline, these figures may again rise. In these cases, the doctor, guided by the clinical picture, must decide whether to cancel treatment and when you can resume.

Through one or more months after discontinuation of treatment of disorders of bone metabolism may occur again in this case, it will require a new course.

Neurodystrophic diseases. Extremely important early diagnosis. Treatment should begin immediately after confirmation of the diagnosis. Appoint 200 IU/day (an injection) daily for 2-4 weeks. Perhaps an additional purpose for ME 200 a day for up to 6 weeks depending on the dynamics of the patient.

The use in children. The experience of the drug Miacalcic solution for parenteral administration and nasal spray in children is limited, therefore it is not possible to give recommendations for this age group.

Use in elderly patients and groups of patients. Extensive experience with the drug Miacalcic solution for parenteral administration and nasal spray in elderly patients suggests that this age group is not marked worsening tolerability or the need to change the dosing regimen. The same applies to patients with reduced renal function or liver disease, although studies specifically for these groups of patients was carried out.

Device nasal spray and instruction manual

Device nasal spray

1. Protective cap prevents contamination of the tip (nozzle) and clogging the exhaust hole. After the drug is introduced, be sure to wear protective cap.

2. The outlet is a small opening through which vybrazhivaet the solution of the drug.

3. The tip device (tube) that is inserted into the nasal passage.

4. Piston — the part of the bottle, a press which operates the device to spray.

5. The dose counter is a window that shows doses. Even unused spray the box red. When starts the use of the drug in the box will be other color characters (see more below).

6. Tube — inside the tube bottle is used to dispense the drug after clicking on the pump.

7. The vial contains the drug in solution in an amount sufficient for at least 14 injections.

The method of preparation of nasal spray for use

You should never shake the bottle because this can lead to the formation of air bubbles inside the bottle that can result in incorrect dosing of the drug.

Unused nazalnam the spray window of the dose counter is red. You must first remove the protective cap.

The first application while holding the device with one or two hands vertically, push down on the plunger 3 times, which will allow air to exit the tube. It has to be done only once to bring the device to a working state. Don't worry if along with the air will be spraying small amounts of solution (it is provided by and does not affect the subsequent number of doses).

It is necessary to note, that after each successive presses on the piston, the color of the window of the dose counter will change.

After the third pressing the window should turn green, which means the device is ready to work.

Thus, the nasal spray is ready to use.

The method of using the nasal spray

Slightly tilt the head forward and insert the tip into the nostril. Make sure the tip is on a line with the bow stroke, to provide a more uniform distribution of the solution.

Push the plunger 1 time.

Remove the tip of the nose and to make a few vigorous breaths nose to prevent leakage of the drug.

You should not clean the nose immediately after administration of the drug.

If the doctor prescribed 2 of the introduction, the second introduction should be done in the other nostril.

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

Checking account doses

Before and after using the spray you should check number in the window of the dose counter. After each use of nasal spray the figure in the window will change. If at a time 1 dose is entered, the previous value is incremented by 1. Nasal spray contains 14 full doses. As always, provided the remainder of the solution in the vial, it is possible to receive 2 additional doses.

When the window appears figure 16, this would mean that the drug is over.

At the bottom of the bottle you may notice a very slight remnant of a solution it is not usable, it is provided.

Additional warnings

You should never attempt to enlarge the hole of the atomizer with a needle or other sharp objects. This will lead to a complete malfunction of the device. Do not disassemble the pump. If you have any doubts it should consult the place where you purchased the product. To assure proper measuring of dose to store and carry the bottle in an upright position. Do not shake the bottle. To avoid sudden changes in temperature. Open the vial should be stored at room temperature. It is suitable for use for a maximum period of 4 weeks.

Overdose:

Symptoms: when parenteral use of the drug Miacalcin nausea, vomiting, flushing and dizziness are dose-dependent nature. Therefore, when an overdose of the drug Miacalcin, applied intranasally, it is possible to expect similar phenomena. However, there are reports of cases where the drug Miacalcin the nasal spray was applied at a dose of 1600 IU at a time and in a dose of 800 ME per day for 3 days, while there were no serious adverse events. There are reports of individual cases of overdose. In case of overdose may develop hypocalcemia with symptoms such as paresthesia, muscle twitching.

Treatment: symptomatic with the development of hypocalcemia — appointment of calcium gluconate.

Special instructions:

The doctor or nurse should thoroughly instruct patients who self-do yourself a subcutaneous injection of the drug.

Before using the product Miacalcic should visually check the condition of the vial and solution. Ampoule the drug should not be damaged, the solution should be clear, colorless and free from inclusions. After a single application of the drug Miacalcic left in the ampoule unused solution of the drug should be disposed of. Before subcutaneous or intramuscular introduction of the drug solution Miacalcic should be heated to room temperature. Long-term use of the drug Miacalcin patients can form antibodies to calcitonin however, this phenomenon usually does not affect clinical efficacy. The phenomenon of "escape", observed mainly in patients with Paget's disease receiving the drug Miacalcin for a long time, was probably due to the saturation of the bonding, not the formation of antibodies. After a break in treatment the therapeutic effect of the drug Miacalcic is restored. In Paget's disease, and other chronic diseases with elevated bone duration of treatment Miacalcin should be from several months to several years. On the background of treatment the concentration of alkaline phosphatase in the blood and the excretion of hydroxyproline with urine is reduced and often normalized. However, it should be borne in mind that in some cases, after the initial decline, these figures may again rise. In these cases, solving the question of cancellation of treatment or about the time of renewal, the physician must be guided by the clinical picture. Through one or more months after discontinuation of treatment of metabolic disorders of bone tissue can occur again, in this case, it will require a new course of treatment Miacalcin.

Since calcitonin salmon is a peptide, there is a likelihood of systemic allergic reactions. There are reports of allergic reactions including isolated cases of anaphylactic shock, which occurred in patients receiving Miacalcic. If you suspect a hypersensitivity of the patient to calcitonin salmon before treatment should conduct a skin test using the diluted sterile solution of the drug Miacalcin.

The drug Miacalcic solution for injection, contains almost no sodium (less than 23 mg).

Effects on ability to drive vehicles and operate machinery. The influence of the drug Miacalcic on the ability to drive vehicles and operate machinery has not been studied. Some of the side effects of the drug, such as dizziness and visual disturbances may adversely affect the ability to drive and perform potentially hazardous activities, require high concentration and psychomotor speed reactions.

Note. With long-term therapy, the formation of antibodies to calcitonin, however, clinical efficacy is usually not affected. The phenomenon of habituation, which occurs mainly in patients with Paget's disease receiving long-term treatment, may be due to saturation of bonding and obviously has nothing to do with the formation of antibodies. The therapeutic effect of the drug Miacalcic is restored after interruption of treatment.