Zola

Zolta is a medicine that affects the processes of bone mineralization and their structure. Included in the category of bisphosphonates.

Indications Zola

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

Assign to prevent manifestations that develop with the destruction of bone tissue associated with fractures of a pathological nature, compression affecting the vertebral trunk, complications associated with surgical procedures, the negative effects of radiation therapy, and in addition with hypercalcemia caused by the progression of malignant tumors.

However, the drug is used in the treatment of people with malignant tumors in a severe degree.

[1], [2]

Release form

The release of a therapeutic drug is realized in the form of a concentrate, inside a bottle with a capacity of 5 ml.

Pharmacodynamics

Zoledronic acid is a bisphosphonate that specifically affects the activity of bone tissue. It slows down the activity of osteoclasts during bone resorption.

The selective effect exerted by bisphosphonates on bones develops due to their high affinity for bone tissues of mineralized character. At the moment, it was not possible to determine the molecular principle of action, which slows down the activity of osteoclasts. Animal tests have demonstrated that the substance slows down bone resorption, without having a negative effect on the formation, mineralization, and mechanical parameters of the bones.

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

• in vivo - slowing down osteoclasts of bone resorption, acting in relation to the structure of microcrystalline bone matrix; interferes with the growth of a neoplasm and has an antiangiogenic effect (it affects the vessels, which causes a decrease in the tumor blood supply) and an analgesic effect;
• in vitro - slowing down osteoblastic reproduction, direct cytostatic effect, pro-apoptostatic effect on tumor cells, cytostatic and synergistic interaction with other anti-tumor drugs, and with it anti-invasive and anti-adhesion activity.

[3], [4], [5],

Pharmacokinetics

Information regarding pharmacokinetic characteristics in case of bone metastases was obtained after performing 1-time and repeated 5 or 15-minute infusion injections of 2, 4, and 8 and 16 mg of the drug to 64 people. It is revealed that the properties of drugs are not tied to the size of the dosage.

Since the beginning of the infusion, the values of drugs inside the plasma quickly increase, reaching a maximum at the end of the infusion procedure. After that, the indicators quickly decline to <10% of Cmax after 4 hours and <1% of Cmax after 24 hours, with successively extended periods of low rates not exceeding 0.1% of Cmax, until the moment of application infusion, which is carried out on the 28th day.

Used in / in the way of zolendronic acid is excreted through the kidneys, the process is carried out in 3 phases. First, at high speed, there is a 2-phase excretion of drugs from the general circulation with a half-life-α equal to 0.24 hours, as well as –β, which is 1.87 hours. After this, a long elimination stage is carried out, the final half-life of γ is 146 hours.

Accumulation of the drug component inside the plasma in the case of repeated infusions conducted at 28-day intervals does not occur.

The active element of the drug does not participate in metabolic processes and is excreted through the kidneys in an unchanged state. During the initial 24 hours, approximately 39 ± 16% of the used batch is recorded inside the urine. The rest of the substance is synthesized with bone tissue, after which it is released back at a low speed from there to the circulatory system and excreted by the kidneys.

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

Experimental tests on animals showed that less than 3% of the substance is excreted in the faeces, on the basis of which it can be assumed that the state of the liver activity does not affect the pharmacokinetic parameters of the drug.

The clearance of the drug inside the kidney correlates with the indicators of QC; inside the kidney, it is approximately 75 ± 33% of the mean QC values, which were 84 ± 29 ml / minute (limits of 22-143 ml / minute) in 64 people with oncology who participated in the testing. The analysis revealed that in patients with CC 20 ml / minute (acute kidney failure), as well as 50 ml / minute (moderate form of the disease), the relative clearance of drugs was 37%, respectively, and 72%. It must be borne in mind that information on patients with a CC level <30 ml / minute is limited.

Zolta has a weak affinity for cellular blood elements. Intraplasmic protein synthesis is rather low (about 56%); it is not tied to the indicators of zoledronic acid inside the body.

[6], [7], [8], [9]

Dosing and administration

The medicine should be administered exclusively by a doctor who has experience treatment with bisphosphonates. Before starting the procedure, you need to make sure that the patient has a sufficient level of hydration.

The drug (5 ml) is dissolved using a 0.5% glucose solution or 0.9% NaCl (0.1 L). The finished substance is administered intravenously, through an IV. Apply Zolta 1 time for a 3-4 week interval. Therapy should last approximately 2–3 months. The minimum interval between use of the drug should be no more than 7 days.

Persons undergoing treatment procedures, should every day use 0.5 g of calcium and 400 IU of calciferol.

[16], [17], [18]

Use Zola during pregnancy

Reliable data on the safety of the drug in pregnant women are missing, which is why it is not used during this segment.

Contraindications

The drug should not be administered to people with severe intolerance towards zoledronic acid or other bisphosphonates. You also need to control the possibility of the development of hyperhydria in individuals with a high risk of HF.

It is forbidden to combine Zolta with other medicines that contain zometa or other substances containing bisphosphonates.

[10], [11], [12], [13], [14],

Side effects Zola

When using the medication, disorders of the hematopoietic system or taste receptors, headaches, dyspepsia, pain in the muscles, dizziness, convulsions and peripheral edema can appear. In addition, epilepsy attacks, conjunctivitis, anorexia, impaired kidney activity, hand or foot tremor, arrhythmia, allergy symptoms, and flu-like conditions.

[15]

Overdose

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

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

Interactions with other drugs

It is required to carefully combine bisphosphonates with aminoglycosides, because they can have an additive effect, due to which serum calcium levels may be reduced for a longer period than necessary.

The drug is carefully used in combination with other substances with potential nephrotoxicity. It is necessary to consider the likelihood of hypomagnesemia during therapy.

There is evidence that individuals who used Zolta along with anti-angiogenic drugs may develop jaw osteonecrosis.

[19]

Storage conditions

Zolta should be kept in a dark place, closed from the penetration of small children.

Shelf life

Zolta can be used for a 36-month period from the time the pharmaceutical substance is manufactured.

Application for children

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

Analogs

Analogues of the medication are the drugs Destron, Zoledo, Aklast and Zoltsid with Blaster, and in addition Zoldriya and Blaster-N, Zoledronate, Zoleum, Zolendronic acid with Zoltero, Zolemeda with Monteron, Zolendran with Zomet and Resorba with Zolotonar, Newzolen and Metacos.

[20]