Золедрэкс

General characteristics. Structure:

Active ingredient: 4 mg of zoledronovy acid.

Pharmacological properties:

Pharmacodynamics. Inhibitor of a resorption of a bone tissue, бисфосфонат. Possesses selective effect on a bone. Has an inhibiting effect on the resorption of a bone tissue mediated by osteoclasts.

The selection action of bisfosfonat on a bone tissue is based on high affinity to the mineralized bone tissue, but the exact molecular mechanism providing inhibition of activity of osteoclasts still remains obscure.

In addition to an inhibiting effect on a resorption of a bone tissue, zolendronovy acid has other antineoplastic properties providing a therapeutic effectiveness at bone metastasises.

In vivo: the inhibition of an osteoklastichesky resorption of a bone tissue changing a marrow microenvironment, leading to decrease in growth of tumor cells; antiangiogenic activity. Suppression of a bone resorption clinically is followed by also expressed decrease in pain.

In vitro: inhibition of proliferation of osteoblasts, direct cytotoxic and proapoptichesky activity, synergy cytostatic effect with antineoplastic drugs; abhesive/invasive activity.

Zoledronovy acid, suppressing proliferation and inducing apoptosis, has direct antineoplastic effect concerning cells of a myeloma of the person and a cancer tumor of a mammary gland, and also reduces penetration of cells of a cancer tumor of a mammary gland through an extracellular matrix that demonstrates existence at it anti-metastatic properties. Besides, zoledronovy acid inhibits proliferation of cells of an endothelium of the person and causes antiangiogenic action in animals.

At patients with the hypercalcemia caused by a tumor it was shown that effect of zoledronovy acid is characterized by decrease in concentration of calcium in serum and reduction of its removal with urine.

Indications to use:

- The hypercalcemia (concentration of the serumal calcium corrected on albumine ≥ 12 mg/dl or 3 mmol/l) induced by malignant tumors.
- Metastatic damage of bones at malignant solid tumors and a multiple myeloma (for decrease in risk of pathological changes, a compression of a spinal cord, the hypercalcemia caused by a tumor and decrease in need for performing radiation therapy).

Route of administration and doses:

Золедрэкс® apply intravenously kapelno, within not less than 15 min.

Hypercalcemia at malignant new growths. At concentration of the serumal calcium corrected on albumine ≥ 12 mg/dl or 3 mmol/l the maximum recommended dose makes 4 mg. Before infusion it is necessary to check concentration of creatinine in blood serum.

Repeated administration of drug in a dose of 4 mg 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. Repeatedly Zoledreks® is entered in a dose of 8 mg within 15 min. The interval before repeated introduction has to make not less than 7 days, it is necessary for implementation of full clinical effect of an initial dose.

Multiple myeloma and metastatic damage of bones at solid tumors. The dose of the drug Zoledreks® depends on initial clearance of the creatinine calculated by Kokrofta-Gault's formula.

After the beginning of therapy concentration of creatinine should be measured in blood serum before each introduction. If function of kidneys worsens, the next administration of drug should be postponed.

To patients it is necessary to appoint zoledronovy acid in addition to therapy calcium inside in a dose of 500 mg a day and vitamin D inside in a dose 400 ME in days.

Features of use:

At repeated use before each introduction it is necessary to define concentration of creatinine in blood serum. If the obtained data confirm deterioration in function of kidneys, it is necessary to estimate risk and advantage of the carried-out therapy.

It is not recommended to apply at patients with heavy renal failures (concentration of serumal creatinine of ≥400 µmol/l or ≥4.5 mg/dl) except for cases when the expected advantage of therapy prevails over potential risk.

Before infusion it is necessary to exclude existence of dehydration at the patient. For ensuring adequate hydration introduction of normal saline solution to, in time or after infusion of zoledronovy acid is recommended. It is necessary to avoid an overhydratation of the patient because of risk of emergence of complications from cardiovascular system.

After introduction of zoledronovy constant control behind concentration of calcium, phosphorus, magnesium and creatinine in blood serum is necessary.

If the hypocalcemia, a hypophosphatemia or a hypomagnesiemia develops, the short-term maintenance therapy is necessary.

There are separate messages on a renal failure against the background of use of bisfosfonat. Treat the previous renal failure and prolonged use of zoledronovy acid in high doses (8 mg) risk factors of development of such complications, reduction of time of infusion.

Efficiency and safety of use of zoledronovy acid in pediatric practice are not established.

Side effects:

Often – pain, irritation, puffiness, formation of infiltrate in a drug injection site; anemia, headache; conjunctivitis; nausea, vomiting, anorexia; ostealgia, mialgiya, arthralgia, generalized pains; renal failures; fever, grippopodobny states.

Other observed undesirable phenomena: thrombocytopenia, leukopenia; dizziness, paresthesias, taste disturbances, hypesthesia, hyperesthesia, tremor, alarm, sleep disorder; sight illegibility; diarrhea, a lock, abdominal pain, dyspepsia, stomatitis, dryness in a mouth; short wind, cough; an itch, rash (including erythematic and makulezny), the increased perspiration; muscular spasms; the expressed increase in arterial pressure; acute renal failure, hamaturia, proteinuria. allergic reactions; adynamy, peripheral hypostasis, thorax pain, increase in body weight; seldom – a pancytopenia; confusion of consciousness; bradycardia; Quincke's disease.

Interaction with other medicines:

At simultaneous use of bisfosfonat and aminoglycosides calcium level in serum can remain reduced is longer, than it is required as the perhaps additive influence on concentration of calcium in blood serum.

At simultaneous use with the drugs which are potentially possessing nephrotoxic action the risk of deterioration in function of kidneys increases.

Contraindications:

• Hypersensitivity to the zoledronovy acid, other bisfosfonata or any other components which are a part of drug;
• initial heavy renal failure (clearance of creatinine of ≤30 ml/min.);
• pregnancy and period of feeding by a breast;
• children's and teenage age (safety and efficiency of use were not studied).

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Bottle from dark glass on 4 mg of lyophilisate in a cardboard pack.