Zolta

Zolta is a drug that affects bone mineralization processes and their structure. It belongs to the category of bisphosphonates.

Indications Zolta

It is used in people with an increased risk of bone tissue resorption.

It is prescribed to prevent manifestations that develop during the destruction of bone tissue associated with pathological fractures, compression affecting the spinal column, complications associated with surgical procedures, negative consequences of radiation therapy, and in addition with hypercalcemia caused by the progression of malignant neoplasms.

Along with this, the drug is used in the treatment of people with severe malignant tumors.

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Release form

The therapeutic drug is released in the form of a concentrate, inside 5 ml vials.

Pharmacodynamics

Zoledronic acid is a bisphosphonate that specifically affects bone tissue activity. It inhibits osteoclast activity during bone resorption.

The selective effect of bisphosphonates on bone is due to their high affinity for mineralized bone tissue. The molecular mechanism of action that inhibits osteoclast activity has not yet been determined. Animal tests have shown that the substance inhibits bone resorption without adversely affecting bone formation, mineralization, or mechanical parameters.

In addition to slowing down the activity of osteoclasts in bone resorption, the drug has a direct antitumor effect that can enhance systemic efficacy during therapy for bone metastases. Preclinical testing has shown the following results:

• in vivo – slowing down of osteoclast bone resorption, acting on the structure of the microcrystalline bone matrix; prevents tumor growth and has an antiangiogenic (acts on blood vessels, due to which the tumor blood supply is weakened) and analgesic effect;
• in vitro – slowing down of osteoblastic proliferation, direct cytostatic effect, proapoptostatic effect on tumor cells, cytostatic and synergistic interaction with other antitumor drugs, and along with this antiinvasive and antiadhesive activity.

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Pharmacokinetics

Information on pharmacokinetic characteristics in bone metastases was obtained after performing single and repeated 5- or 15-minute infusions of 2, 4, and 8 and 16 mg of the drug in 64 people. It was found that the properties of the drug are not tied to the dosage size.

From the start of the infusion, plasma LS values increase rapidly, reaching a maximum at the end of the infusion procedure. After this, the values quickly decrease to <10% of Cmax after 4 hours and <1% of Cmax after 24 hours, with a consistently prolonged period of low values, not exceeding 0.1% of Cmax, until the moment of the new infusion, which is carried out on the 28th day.

Zoledronic acid administered intravenously is excreted through the kidneys, a process that occurs in 3 phases. First, a 2-phase excretion of the drug from the general circulation occurs at a high rate with a half-life of 0.24 hours, as well as -β, which is 1.87 hours. This is followed by a prolonged elimination phase, the final half-life of which is 146 hours.

There is no accumulation of the medicinal component in the plasma in the case of repeated infusions carried out at 28-day intervals.

The active element of the drug does not participate in metabolic processes and is excreted through the kidneys unchanged. During the initial 24 hours, approximately 39±16% of the used portion is recorded in the urine. The remainder of the substance is synthesized with bone tissue, after which it is released back into the circulatory system at a low rate and excreted by the kidneys.

Overall clearance values are approximately 5.04±2.5 L/h. Prolonging the infusion time from 5 to 15 minutes reduces drug values by the end of the procedure by 30%, but does not affect plasma AUC values.

Experimental tests on animals have shown that less than 3% of the substance is excreted in the feces, which suggests that the state of liver function does not affect the pharmacokinetic parameters of the drug.

Renal clearance of the drug correlates with the CC values; in the kidneys it is approximately 75±33% of the mean CC values, which were 84±29 ml/minute (range 22-143 ml/minute) in 64 people with oncology who participated in the testing. The analysis showed that in people with CC of 20 ml/minute (acute renal failure) and 50 ml/minute (moderate form of the disease), the relative clearance values were equal to 37% and 72%, respectively. It should be taken into account that information on patients with CC levels <30 ml/minute is limited.

Zolta has a low affinity for cellular blood elements. Intraplasmic protein synthesis is quite low (approximately 56%); it is not related to the intra-organism levels of zoledronic acid.

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Dosing and administration

The drug should only be administered by a doctor experienced in treating with bisphosphonates. Before starting the procedure, make sure the patient is adequately hydrated.

The medicine (5 ml) is dissolved using a 0.5% glucose solution or 0.9% NaCl (0.1 l). The finished substance is administered intravenously through a dropper. Zolt should be used once every 3-4 weeks. The therapy should last approximately 2-3 months. The minimum interval between uses of the medicine should not exceed 7 days.

People undergoing medical procedures should consume 0.5 g of calcium supplements and 400 IU of calciferol daily.

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Use Zolta during pregnancy

There is no reliable data regarding the safety of the drug in pregnant women, which is why it is not used during this period.

Contraindications

The drug should not be prescribed to people with severe intolerance to zoledronic acid or other bisphosphonates. The possibility of hyperhydria in people with a high risk of developing heart failure should also be monitored.

It is prohibited to combine Zolta with other medications that contain zometa or other substances containing bisphosphonates.

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Side effects Zolta

When using the medicine, disorders of the hematopoietic system or taste buds, headaches, dyspepsia, muscle pain, dizziness, cramps and peripheral edema may occur. In addition, epileptic seizures, conjunctivitis, anorexia, kidney dysfunction, tremors of the hands or feet, arrhythmia, allergy symptoms and flu-like conditions may occur.

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Overdose

The use of large doses of the drug can lead to the destruction of the electrolyte structure of the blood serum or to the emergence of problems in the functioning of the kidneys.

If the patient develops symptoms of hypocalcemia, calcium gluconate should be administered intravenously.

Interactions with other drugs

Bisphosphonates should be combined with aminoglycosides with caution because they may have additive effects, which may result in serum calcium levels being lowered for a longer period than necessary.

The drug is used with caution in combination with other substances that have potential nephrotoxicity. It is also necessary to consider the possibility of hypomagnesemia during therapy.

There is evidence that individuals who used Zolta together with antiangiogenic drugs may develop jaw osteonecrosis.

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Storage conditions

Zolta should be stored in a dark place, out of the reach of small children.

Shelf life

Zolta can be used for a period of 36 months from the date of manufacture of the pharmaceutical substance.

Application for children

It is not known whether Zolta is safe to use in children under 17 years of age; there is also no information regarding the effectiveness of the drug in this category of patients.

Analogues

Analogues of the drug are the drugs Deztron, Zoledo, Aclasta and Zolcid with Blazter, and in addition to this, Zoldria and Blazter-N, Zoledronate, Zoleum, Zoledronic acid with Zoltero, Zolemeda with Monteron, Zolendran with Zometa and Resorba with Zolonar, Newzolen and Metakos.

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