Zoledronovy acid

General characteristics. Structure:

Active ingredient: 4 mg of zoledronovy acid.

Pharmacological properties:

Pharmacodynamics. Belongs to the new class of the highly effective bisfosfonat possessing selective selection effect on a bone tissue. The selection action is caused by high affinity to the mineralized bone tissue, however, the exact molecular mechanism providing inhibition of activity of osteoclasts still remains obscure. Zoledronovy acid inhibits a resorption of a bone tissue, without making at the same time undesirable impact on formation, a mineralization and mechanical properties of a bone. The inhibition of an osteoklastny resorption of a bone tissue changing a marrow microenvironment leads to decrease in growth of tumor cells; antiangiogenic and analgetic activity is noted. Zoledronovy acid suppresses also proliferation of cells of an endothelium of the person. At the hypercalcemia caused by a tumor reduces concentration of Ca2 + in blood serum.

Indications to use:

- the osteolytic, osteosclerotic and mixed bone metastasises of solid tumors;

- the osteolytic centers at a multiple myeloma (as a part of a combination therapy);

- the hypercalcemia caused by a malignant tumor.

Route of administration and doses:

In/in kapelno, within 15 minutes. At bone metastasises and the osteolytic centers at a multiple myeloma as a part of a combination therapy the recommended dose - 4 mg. Frequency rate of introduction - each 3-4 weeks.

At the hypercalcemia caused by a malignant tumor: at concentration of Ca2 +-1,2 mg/ml, or 3 mmol/l on concentration of albumine the recommended dose - 4 mg. Infusion is carried out on condition of adequate hydration of the patient. Repeated administration of drug is shown in case of an aggravation of symptoms after clear effect (i.e. achievements of concentration of Ca2 + in blood serum of 2,7 mmol/l and below) or in case of a refrakternost to the first introduction. It is repeatedly entered in a dose of 8 mg within 15 min. The interval between the first and repeated introduction has to be not less than 1 week for effect assessment. Usually reached effect of decrease in Ca2 + in blood remains within 30 days after introduction of 4 mg and within 40 days after introduction of 8 mg.

Correction of the mode of dosing is not required from patients with a weak or moderate renal failure. In need of repeated introduction it is necessary to define concentration of creatinine of blood serum before each infusion.

Preparation of injection solution: solution is prepared in aseptic conditions - 4 mg dissolve in 5 ml of water for injections (8 mg - in 10 ml respectively), carefully stir up before full dissolution. The received solution with a necessary dose dissolve 0.9% of NaCl solution or 5% of solution of a dextrose in 50 ml.

Not to use the solutions containing Ca2+. To use solution of medicine right after preparation.

Features of use:

To use only freshly cooked solutions. As solvents it is impossible to use the solutions containing Ca2+, in particular Ringer's solution.

Due to a possibility of clinically significant deterioration in function of kidneys up to a renal failure, the single dose should not exceed 4 mg and duration of infusion has to make not less than 15 min.

It is not necessary to mix solution of zoledronovy acid in one syringe with other medicines.

Side effects:

From water and electrolytic exchange: hypophosphatemia, hypocalcemia, hypomagnesiemia; disturbance of exchange of K+ (both hyperpotassemia, and hypopotassemia), hypernatremia.

From bodies of a hemopoiesis: thrombocytopenia, anemia, leukopenia, pancytopenia. From the alimentary system: nausea, vomiting, a loss of appetite, locks or diarrhea, an abdominal pain, dyspepsia, stomatitis, dryness in a mouth.

From a nervous system: a headache, weakness, paresthesias, a hypesthesia, a hyperesthesia, a tremor, uneasiness, frustration of a dream, the confused consciousness.

From sense bodys: disturbance of flavoring feelings, conjunctivitis, sight "misting".

From an urinary system: renal failure (increase in serumal concentration of creatinine and urea), acute renal failure, hamaturia, proteinuria.

From respiratory system: диспноэ, cough.

From integuments: an itch, rash (including erythematic and macular), the increased sweating.

From a musculoskeletal system: ostealgias, mialgiya, arthralgia, myotonia.

Allergic reactions: extremely seldom - skin rash, an itch, a Quincke's disease. Local reactions: pain, irritation, a swelling, formation of infiltrate in an injection site.

Others: heat, grippopodobny syndrome (fever, fever, ostealgia and/or muscles); adynamy, peripheral hypostases, increase in body weight, thorax pain, bradycardia.

Interaction with other medicines:

At simultaneous use with antineoplastic medicines, antibiotics, analgetics of clinically significant interactions it is noted.

With care appoint in combination with loopback diuretics (the risk of a hypocalcemia increases), other potentially nefrotoksichny medicines.

Aminoglycosides exert the unidirectional impact on concentration of Ca2 + in blood serum therefore at their co-administration the risk of development of a hypocalcemia and hypomagnesiemia increases.

At patients with a multiple myeloma increase in risk of a renal failure at simultaneous use of a thalidomide is possible.

Contraindications:

Hypersensitivity (including to other biphosphonates), pregnancy, the lactation period, children's and teenage age.

With care: heavy renal (concentration of creatinine in blood serum not less than 400 µmol/l or 4.5 mg/dl) or a liver failure, "aspirinovy" bronchial asthma.

Overdose:

Symptoms: strengthening of symptoms of a hypocalcemia, hypophosphatemia, hypomagnesiemia.

Treatment: intravenous administration of calcium of a gluconate, sodium/potassium of phosphate, sulfate magnesium.

Issue conditions:

According to the recipe

Packaging:

The powder lyophilized for preparation of solution for infusions of 4 mg in bottles in packaging No. 1, No. 40.