Calcitonin

When ATH:
H05BA01

Characteristic.

Polypeptide Hormone, regulator of calcium-phosphorus metabolism.

In mammals and humans is synthesized primarily parafollicular or C cells of the thyroid glands; fish, amphibians, reptiles and birds produced in the so-called corpuscles ultimobranhialnyh, emerging from the last pair of gill arches. In human calcitonin is secreted not only in the thyroid gland, but also in the thymus and parathyroid. Developed synthetic methods for producing calcitonin. There are 8 types of calcitonin, of which the most common medical practice Synthetic salmon calcitonin, recombinant porcine calcitonin and human calcitonin. Salmon calcitonin has bólshey biological activity, than the endogenous human calcitonin, and longer duration of action.

Drug activity is expressed in U or IU, and is determined by a biological or radioimmunoassay. In determining the method for biological activity 1 ED as the amount of hormone, causing a decrease in certain experimental conditions, the calcium content in the blood 10% rats. 1 IU matches 0,2 mg pure peptide (Synthetic salmon calcitonin).

Calcitonin drugs used parenterally (due to hydrolysis in the stomach) and intranasally.

Pharmacological action.
Gipokaltsiemicheskih, inhibits bone resorption, analgesic.

Application.

Systemic diseases with the restructuring of the skeleton (Paget's disease, brittle bones, spontaneous bone resorption, quiet hip disease); osteoporosis (postmenopauzny, senile, steroidal, parathyroid et al.), fibroznaya dysplasia, traumatic injury to the bone with complicated repair process (delayed fracture healing); osteomyelitis (traumatic, radiation), zonal abnormal bone remodeling in athletes, parodontoz, complex regional pain syndrome, Family hyperphosphatemia, hypercalcemia of various origins (incl. idiopathic hypercalcemia newborns), thyrotoxicosis, Myeloma, bone metastases, гипервитаминоз D, prevention of bone disorders resulting from prolonged immobilization; ostealgias, associated with osteolysis and / or osteopenia; acute pancreatitis (in a combination therapy).

Contraindications.

Hypersensitivity, hypocalcemia, childhood (experience of calcitonin in children is limited).

Pregnancy and breast-feeding.

Application during pregnancy is possible only in case of, if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies of the safety of use in pregnant women were not conducted), Use as a spray during pregnancy was shown.

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Should not be used during breastfeeding (unknown, whether calcitonin penetrates into the breast milk of women; shows, Calcitonin inhibits lactation in animals).

Side effects.

According to the State Register of Medicinal Products, 2004

General: allergic reactions - local or generalized, including anaphylactic shock (tachycardia, low blood pressure, collapse), flushing, increased blood pressure, arthralgia, edema (person, limbs, generalized edema); bad taste in mouth.

For parenteral administration: dizziness, headache; nausea, vomiting, gastralgia, diarrhea; myalgia, pharyngitis, fatigue, dysgeusia; cough, flu-like symptoms, visual disturbances, polyuria; Local reactions - redness and soreness at the injection site.

Intranasal application: rhinitis, erosion of the nasal mucosa, dry and / or swelling of the nasal mucosa, chikhaniye, papulation nasal, sinusitis, nose bleed.

According to Physicians Desk Reference, 2005

For parenteral administration of salmon calcitonin following adverse effects were noted:

From the digestive tract: nausea with / without vomiting (approximately 10% patients), were more pronounced at the beginning of the introduction, and decreased or disappeared when its sequel.

Dermatological / hypersensitivity reactions: Local reactions - inflammation at the s / c or i / m administration (about 10%); flushing (about 2-5%), skin rash, nocturia, itchy earlobes, feeling the heat, sore eyes, decreased appetite, abdominal pain, swelling of the feet, dysgeusia; It reported several cases of severe allergic reactions (bronchospasm, swelling of the tongue or throat, anaphylactic shock), one case of death due to anaphylaxis (cm. Precautions).

When using salmon calcitonin in the form of a nasal spray in patients with postmenopausal osteoporosis observed adverse events, shown in Table.

Table

Side effects, ≥3% were observed in patients with post-menopausal osteoporosis in the long-term treatment with calcitonin (salmon)

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Normal 0 21 false false false UK X-NONE X-NONE MicrosoftInternetExplorer4

* The symptoms from the nose, incl. crusting and dryness of the nasal cavity, redness or erythema, soreness, irritation, itch, feeling seals, pale mucous, infection, Education krovotochaschyh morning, pain and discomfort around the nose.

Studies to assess the interaction of drugs with salmon calcitonin is not carried out. Cases of drug interactions with salmon calcitonin have been reported. In the treatment of hypercalcemia of simultaneous use of calcium-containing drugs or of vitamin D can counteract the effect of calcitonin; to treat other conditions calcium-containing preparations may be administered through 4 hours after calcitonin.

Overdose.

Symptoms: signs of hypocalcemia (paresthesia, muscle twitching and others.). When s / to a calcitonin (salmon) dose 1000 IU observed only nausea and vomiting. At doses up to 32 IU / kg / day registered during 1-2 days of additional adverse effects. These long-term application of high doses are insufficient to assess toxicity.

Intranasal application of overdoses and serious side effects, associated with the use of high doses of, not observed. There are reports that a single application of a nasal spray salmon calcitonin at a dose of 1600 ME and applied at a dose 800 IU / day for 3 days, with serious side effects were noted. On the development of hypocalcemic tetany when using a nasal spray has not been reported.

Treatment: symptomatic. Parenteral administration of calcium gluconate.

B /, / m, n / a, intranasally. Dose, mode and route of administration chosen individually, taking into account the evidence and the severity of the patient's condition.

Caution should be exercised when administered to patients, prone to allergic reactions, Considering the structure of the peptide drug. Several cases of severe allergic reactions and a lethal outcome when applying injection form of salmon calcitonin (cm. Side effects). For emergency assistance in the event of such reactions, you must have the appropriate software. Allergic reactions should be differentiated from generalized tides and hypotension. In clinical trials and market research in the form of salmon calcitonin nasal spray, serious allergic-type reactions were noted.

Before the treatment is carried out a skin test, especially in cases of suspected hypersensitivity of the patient to calcitonin, and determining the content of calcium in the blood. Patients with low calcium levels (less 10 mg%) or severe skin reaction to calcitonin (эritema, swelling) no treatment. An increase in blood pressure, flushing should take a break in treatment for 2-3 days, and in case of repeated reactions - stop the drug.

The first introduction of calcitonin (or more of the initial introductions) may develop hypocalcaemia, sometimes accompanied by tetany, however for emergency assistance should be available calcium preparation (kalytsiya gluconate) for parenteral administration.

With prolonged use of salmon calcitonin, which is alien to the human body protein, possible formation of antibodies. With short-term use (2 year or less) appearance of antibodies was observed in 30-60% of patients, but only 5-15% as a result of drug resistance emerged. Carrying a long-term treatment is possible only in those patients, which is not observed the formation of antibodies. Since the synthetic human calcitonin is identical to the natural, antibodies is rare, which allows for a long course treatment, does not lead to the development of resistance.

With Paget's disease, and other chronic conditions, characterized by increased bone exchange, during treatment with calcitonin significantly reduced levels of serum alkaline phosphatase (reflecting a decrease of osteogenesis) and decreases hydroxyproline excretion in the urine (reflecting a decrease in bone resorption, in particular, cleavage of collagen). The most pronounced decline in these indicators, reflecting the positive effects of therapy, It observed after 6-24 months of treatment. It should monitor the level of alkaline phosphatase in serum and the daily urinary excretion of hydroxyproline before treatment, regularly in the first 3 months of treatment and every 3-6 months during long-term treatment.

In the treatment of patients with hypercalcemia systematic control calcium levels in the blood.

When long-term therapy is recommended periodic examination of urine sediment. It has been reported about the appearance of urinary cylinders (granular cylinders and cylinders, containing epithelial cells of renal tubules) in healthy young volunteers, It is on bed rest (used injectable form of salmon calcitonin in the study of immobilization osteoporosis). After stopping calcitonin any renal disorders were observed and urine sediment became normal.

In the treatment of osteoporosis with calcitonin, simultaneously ensure adequate intake of calcium and vitamin D (to prevent the progressive loss of bone mass).

When using a nasal spray before treatment and periodically during the inspection of a therapy with visualization of the nasal mucosa, turbinates, septa, blood vessels of the nasal mucosa.

All postmenopausal patients, ispolyzovavshih spray, In most cases, there are side Nasal reatsiya, as rhinitis (12%), nose bleed (3,5%) E sinusitis (2,3%). Smoking did not affect the expression of nasal adverse reactions. One patient (0,3%) in treating in a dose spray 400 IU daily had a small nasal wound. In clinical trials, Paget's disease in 2,8% patients developed nasal ulcerations.

If there is marked ulceration of the nasal mucosa (more 1,5 mm in diameter) or penetrating the mucous, or associated with severe bleeding, Use spray should be discontinued. Although small ulcers often heal without withdrawal of the drug, should temporarily discontinue treatment before their healing.

Intranasal administration requires caution in patients with chronic rhinitis.

It is recommended to be very careful when driving vehicles and operating machinery.