Zolerix - Instructions For Use, Price, Reviews, Drug Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Zolerix

Zolerix: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Zolerix

ATX code: M05BA08

Active ingredient: zoledronic acid (Zoledronic acid)

Manufacturer: CJSC "Biocad" (Russia)

Description and photo update: 2019-09-07

Prices in pharmacies: from 6138 rubles.

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Zolerix is a bisphosphonate, an inhibitor of bone resorption in bone metastases.

Release form and composition

The drug is available in the form of a concentrate for the preparation of a solution for infusion: a clear, colorless liquid (5 or 6.25 ml in plastic or glass bottles, a cardboard box of 1 or 5 bottles and instructions for use of Zolerix).

1 ml of concentrate contains:

• active substance: zoledronic acid monohydrate (in terms of dry matter) - 0.8 mg;
• auxiliary components: mannitol, sodium citrate dihydrate, water for injection.

Pharmacological properties

Pharmacodynamics

Zolerix is a medication that prevents bone loss (bisphosphonate). Its active ingredient, zoledronic acid, has a selective inhibitory effect on osteoclast-mediated bone resorption. It is assumed that selective inhibition of osteoclast activity is associated with the high affinity of bisphosphonates for mineralized bone tissue. In addition, the presence of other antitumor properties in zoledronic acid provides a therapeutic effect of the drug in bone metastases.

The results of studies in vivo confirm that due to changes in the microenvironment of the bone marrow against the background of inhibition of osteoclastic resorption of bone tissue, there is a decrease in the growth of tumor cells. The drug is characterized by anti-angiogenic activity, a clinically pronounced decrease in pain, accompanying the suppression of bone resorption.

In vitro studies indicate inhibition of osteoblast proliferation, direct cytotoxic and proapoptic activity, antiadhesive or invasive action. The synergism of the cytostatic effect with antitumor agents of concomitant therapy was established.

By inhibiting proliferation and inducing apoptosis, zoledronic acid has an antitumor effect directly against human myeloma cells and breast cancers. Evidence of the antimetastatic properties of Zolerix is a decrease in the ability of breast cancer cells to overcome the extracellular matrix. In addition, zoledronic acid inhibits the proliferation of endothelial cells and causes an anti-angiogenic effect.

In tumor-related hypercalcemia, the action of zoledronic acid helps to reduce serum calcium concentration and reduce its excretion in the urine.

Pharmacokinetics

The pharmacokinetics of zoledronic acid does not depend on its dose.

After the start of intravenous (IV) administration, the maximum concentration (C _max) of zoledronic acid in plasma is reached by the end of the infusion. This is followed by a rapid decrease in its level, after 4 hours the concentration of zoledronic acid in plasma decreases by 10% and after 24 hours - by less than 1%. A consistently prolonged period of low concentrations allows maintaining the concentration of the active substance in plasma at a level of up to 0.1% of C _max until repeated infusion after 27 days.

Zoledronic acid has a low affinity for blood components. Plasma protein binding is low (the proportion of unbound fraction is 60-77%) and does not depend on the concentration of zoledronic acid.

With repeated injections with an interval of 28 days, no cumulation was observed.

Zoledronic acid does not undergo systemic metabolism. It is excreted from the systemic circulation through the kidneys unchanged in 3 stages. The first two stages pass quickly, their half-life (T _1/2) is 0.24 hours and 1.87 hours, followed by the final T _1/2 phase, which lasts 146 hours.

In the urine during the first 24 hours, an average of 39% of the administered dose is found, the rest is mainly associated with bone tissue. This is followed by a slow release of zoledronic acid from the bone tissue back into the systemic circulation, followed by excretion by the kidneys. The total plasma clearance averages 5.04 l / h.

By the end of the infusion lasting 1/4 hour, the concentration of zoledronic acid in plasma decreases by 30% from the level achieved with IV administration of Zolerix for 1/12 hour, the AUC (area under the concentration-time curve) does not change.

Up to 3% of the dose is excreted through the intestines.

The renal clearance of zoledronic acid is positively correlated with creatinine clearance (CC) and is equal to 75 ± 33% of CC, which is in the range from 22 to 143 ml / min.

With mild (CC 50–80 ml / min) and moderate (CC 30–50 ml / min) degree of renal dysfunction, dose adjustment of zoledronic acid is not required.

In severe renal impairment (CC less than 30 ml / min), the use of Zoleriks is contraindicated due to the increased risk of renal failure.

There is no information on the pharmacokinetics of zoledronic acid in patients with impaired liver function. But given that zoledronic acid does not undergo biotransformation and does not inhibit the isozymes of the human cytochrome P ₄₅₀ system, a significant effect of the state of liver function on its pharmacokinetics is not expected. Therefore, dose adjustment of Zolerix is not required in patients with impaired liver function.

Indications for use

• bone metastases in breast cancer, prostate cancer and other solid malignant tumors, osteolytic foci in multiple myeloma, including in order to reduce the risk of spinal cord compression, pathological fractures, development of hypercalcemia against the background of the tumor and to reduce the need for radiation therapy or bone surgery;
• hypercalcemia due to malignant neoplasms [serum calcium concentration, adjusted for albumin, is more than 12 mg / dL (3 mmol / L)].

Contraindications

Absolute:

• severe renal dysfunction with CC less than 30 ml / min (for prescription for oncological indications);
• period of pregnancy;
• breast-feeding;
• age up to 18 years;
• established hypersensitivity to other bisphosphonates;
• individual intolerance to the components of the drug.

It is recommended to prescribe Zolerix with caution in case of mild to moderate renal dysfunction, severe liver dysfunction, concomitant therapy with aminoglycosides, diuretics, calcitonin and other drugs that can potentiate the development of hypocalcemia, as well as with the simultaneous use of drugs with nephrotoxic action and in combination with anti-angiogenic agents.

Zolerix, instructions for use: method and dosage

A ready-made solution of Zolerix concentrate is applied intravenously by drip, using a valve infusion system, which provides a constant rate of administration for at least 1/4 hour.

Compliance with the rules of asepsis is required during the preparation and administration of the infusion. To prepare an infusion solution, the contents of one vial (4 or 5 mg) or another dose of zoledronic acid should be mixed with 100 ml of 0.9% sodium chloride solution or 5% dextrose solution. It is necessary to visually make sure that the finished solution does not contain undissolved particles and does not change color. If there are no deviations, you should proceed with the introduction procedure.

The procedure should only be performed by qualified professionals with experience in the administration of bisphosphonates.

Store unused solution in the refrigerator at 2-8 ° C. Before introduction, it must be removed from the refrigerator in advance so that it can reach room temperature. The solution remains stable for 24 hours, the countdown begins from the moment the concentrate is diluted in the infusion solution and ends at the end of the procedure, including its storage in the refrigerator and the period of infusion.

The remains of the concentrate in the vial must be disposed of.

For intravenous administration of the drug, a separate infusion system should be used. Do not mix Zolerix solution with other medicines, Ringer's lactate solution or other solutions containing divalent cations (including calcium).

Before the introduction of zoledronic acid, you should make sure that the patient's body is normally hydrated, especially in patients over the age of 65 or taking diuretics. For the purpose of adequate hydration, the use of 0.9% sodium chloride solution is indicated.

Recommended dosage of Zolerix:

• bone metastases in malignant solid tumors, multiple myeloma: 4 mg with an interval between infusions of 21-28 days. Combination therapy includes the simultaneous use of calcium by mouth in a daily dose of 500 mg and vitamin D in a daily dose of 400 IU (international units);
• hypercalcemia due to malignant neoplasms: no more than 4 mg once.

The decision on the appointment of zoledronic acid for severe renal dysfunction in patients with hypercalcemia caused by malignant tumors should be made only in cases where the expected effect of therapy outweighs the existing risks. Correction of the dosage regimen is not required if the serum creatinine level is less than 400 μmol / L (4.5 mg / dL).

With mild to moderate renal impairment (CC 30-60 ml / min) in patients with metastatic bone lesions with malignant solid tumors and multiple myeloma, the dose of Zolerix is prescribed taking into account the initial CC value, which should then be determined before each next infusion.

The recommended dosage of Zolerix, taking into account the patient's CC:

• CC more than 60 ml / min: 4 mg, which corresponds to 5 ml of concentrate;
• CC 50-60 ml / min: 3.5 mg, which corresponds to 4.4 ml of concentrate;
• CC 40–49 ml / min: 3.3 mg, which corresponds to 4.1 ml of concentrate;
• CC 30–39 ml / min: 3 mg, which corresponds to 3.8 ml of concentrate.

The next administration of zoledronic acid should be postponed if the following deterioration in renal function is found:

• the creatinine level is exceeded by 0.5 mg / dl in patients with a baseline serum creatinine concentration of less than 1.4 mg / dl;
• the creatinine level is exceeded by more than 1 mg / dl in patients with a baseline serum creatinine concentration of more than 1.4 mg / dl.

After the restoration of the creatinine concentration levels within ± 10% of the initial value, drug therapy can be resumed at the dose used until the interruption of treatment.

In case of impaired liver function and in patients over the age of 65, dose adjustment of Zolerix is not required.

Side effects

Criteria for assessing the occurrence: very often - ≥ 10%; often - from ≥ 1% to <10%; infrequently - from ≥ 0.1% to <1%; rarely - from ≥ 0.01% to <0.1%; very rarely - <0.01%; frequency not established - according to the messages, it is not possible to establish the frequency of occurrence of undesirable reactions:

• from the lymphatic system and blood: often - anemia; infrequently - leukopenia, thrombocytopenia; rarely - pancytopenia;
• from the gastrointestinal tract: often - decreased appetite, nausea, constipation, vomiting; infrequently - dry mouth, stomatitis, diarrhea, dyspepsia, abdominal pain;
• from the immune system: infrequently - hypersensitivity reactions; rarely - angioedema; frequency not established - anaphylactic reaction, shock;
• from the nervous system: often - paresthesia, headache; infrequently - dysgeusia, hyperesthesia, hypesthesia, tremor, dizziness; very rarely - convulsions, against the background of hypocalcemia - tetany and hypoesthesia; frequency not established - drowsiness;
• from the side of the vessels: often - increased blood pressure (BP); infrequently - lowering blood pressure; the frequency has not been established - a decrease in blood pressure, leading to fainting or circulatory collapse (more often occurs in patients with risk factors);
• from the side of the heart: rarely - bradycardia; frequency not established - atrial fibrillation;
• on the part of the organ of vision: often - conjunctivitis; infrequently - blurred vision; rarely - uveitis; frequency not established - scleritis, episcleritis, inflammatory diseases of the orbit;
• from the respiratory system, chest and mediastinal organs: infrequently - cough, shortness of breath; rarely - interstitial lung disease; frequency not established - bronchospasm;
• from the musculoskeletal system and connective tissue: often - joint stiffness, myalgia, arthralgia, bone pain, generalized pain; infrequently - muscle cramps, lower jaw necrosis; very rarely - osteonecrosis of the external auditory canal; frequency not established - pain in bones, joints and / or muscles, limiting the ability to work, sudden significant limitation of joint mobility, atypical diaphyseal and subtrochanteric fractures of the femur;
• from the urinary system: often - renal dysfunction; infrequently - hematuria, proteinuria, acute renal failure;
• mental disorders: often - sleep disturbance; infrequently - anxiety; rarely - confusion of consciousness;
• dermatological reactions: often - increased sweating; infrequently - itching, skin rash (including erythematous, macular); frequency not established - urticaria;
• general disorders: often - fever, acute phase reaction, flu-like condition (including general malaise, chills, hot flashes), asthenia, peripheral edema; infrequently - weight gain, chest pain;
• local reactions: infrequently - reactions at the injection site (irritation, pain, swelling, redness, induration);
• laboratory parameters: very often - hypophosphatemia; often - hypocalcemia, an increase in the level of creatinine and urea in the blood; infrequently - hypokalemia, hypomagnesemia; rarely - hypernatremia, hyperkalemia.

Overdose

Symptoms: there is limited evidence that with an acute overdose of Zolerix, renal dysfunction may occur, including changes in the electrolyte composition (including a decrease in the content of phosphates, calcium, magnesium in the blood plasma), renal failure.

Treatment: with the appearance of clinical manifestations of hypocalcemia - numbness, tingling sensations (especially in the mouth), muscle spasms - it is necessary to prescribe intravenous administration of solutions containing magnesium, calcium and phosphate ions. The patient's condition should be closely monitored.

special instructions

Initiate zoledronic acid infusion when adequate patient hydration is confirmed. If necessary, the introduction of 0.9% sodium chloride solution is indicated before, simultaneously or after the introduction of Zoleriks. Overhydration of the patient should not be allowed due to the risk of complications from the cardiovascular system.

After Zolerix infusion, regular monitoring of serum creatinine, calcium, phosphorus and magnesium levels is required. If a patient develops hypocalcemia, hypophosphatemia, or hypomagnesemia, short-term additional administration of appropriate agents is indicated. In untreated hypercalcemia, kidney function should be monitored regularly.

When prescribing Zolerix to patients with bone metastases in order to reduce the risk of pathological fractures, compression of the spinal cord caused by a tumor of hypercalcemia, or the need for surgical interventions on bones or radiation therapy, it should be borne in mind that the clinical effect after starting treatment with zoledronic acid occurs only after 2-3 months …

Against the background of the use of bisphosphonates, there is a risk of impaired renal function with repeated or rapid administration of them, dehydration, with previous renal failure, with concomitant therapy with nephrotoxic drugs. The likelihood of impaired renal function persists if zoledronic acid is administered at a dose of 4 mg for at least 1/4 hour. Cases of impaired renal function and progression of renal failure (including with the emergence of the need for hemodialysis) are known with a single or first administration of zoledronic acid. In some patients, an increase in serum creatinine levels was observed with long-term use of Zolerix at recommended doses. When prescribing zoledronic acid to patients with hypercalcemia caused by a malignant tumor,and concomitant renal impairment, an assessment of the patient's clinical condition should be given and the expected potential benefits of therapy and the possible risks should be compared.

The results of clinical observations indicate that osteonecrosis of the jaw most often occurs in advanced breast cancer and myeloma, if the patient has dental pathologies (including tooth extraction, periodontal disease, poor fixation of dentures). Known risk factors for the development of osteonecrosis of the jaw include: cancer, concomitant use of glucocorticosteroids, antiangiogenic drugs, chemotherapy or radiation therapy, the patient has a previous oral disease, anemia, coagulopathy, infection.

The use of bisphosphonates for cancer can only be started after a dental examination and all the necessary preventive procedures. During the period of treatment with zoledronic acid, it is recommended to strictly observe oral hygiene and avoid dental operations.

Osteonecrosis of the external auditory canal often occurs against the background of prolonged use of Zolerix. The risk of its development increases with chemotherapy, taking glucocorticosteroids, infections, local injuries, and the presence of chronic ear infections in patients.

With prolonged use of bisphosphonates for osteoporosis, atypical subtrochanteric and diaphyseal fractures of the femur may occur. Placement of transverse or short oblique fractures is possible on any part of the femur from the supracondylar fossa to the lesser trochanter, they are characterized by spontaneous appearance or occurrence against the background of minimal trauma and slow healing. Before a complete (complete) hip fracture, the patient may experience pain in the hip or groin for several months, which in most cases is accompanied by visual symptoms of stress fractures. In this regard, patients should be warned about the need to immediately consult a doctor for any pain in the hip or groin area in order to establish their cause. The fracture often occurs on both sides,therefore, if a fracture of one femur occurs, an examination of the contralateral femur is necessary. A causal relationship between zoledronic acid therapy and such fractures has not been established. Therefore, if an atypical femoral fracture is suspected, discontinuation of Zolerix should be considered based on an individual assessment of the risk / benefit ratio of treatment.

Against the background of a single injection of zoledronic acid or its use for several months, severe pain in the joints, muscles and bones may occur. In most cases, canceling Zolerix resulted in their termination.

The development of severe hypocalcemia in patients receiving zoledronic acid can be life-threatening and be accompanied by the appearance of such adverse events from the nervous system as convulsions, numbness, tetany, and cardiac arrhythmia.

Before starting the use of Zolerix, you should determine the level of calcium in the blood plasma and, if necessary, correct hypocalcemia by prescribing treatment with calcium and vitamin D.

If the patient has disorders of mineral metabolism, their therapy should be carried out.

It is recommended to use Zolerix with caution in patients with aspirin bronchial asthma due to the risk of bronchoconstriction.

The simultaneous use of the drug with other bisphosphonates is contraindicated.

Influence on the ability to drive vehicles and complex mechanisms

The effect of zoledronic acid on the patient's ability to drive vehicles or work with complex mechanisms has not been established, therefore, due to the existing risk of side effects in the form of dizziness or drowsiness, it is recommended to be careful when performing those activities that require concentration of attention and high speed of psychomotor reactions …

Application during pregnancy and lactation

The use of Zolerix is contraindicated during gestation and breastfeeding.

During the period of treatment, women of reproductive age must use reliable methods of contraception. Conception during therapy with zoledronic acid can cause intrauterine fetal malformations.

Pregnancy planning after bisphosphonate therapy should be discussed with a specialist.

The effect of zoledronic acid on fertility has not been established.

Pediatric use

There is no information on the efficacy and safety of the use of zoledronic acid in pediatric practice, therefore, the appointment of the drug Zolerix is contraindicated in patients under 18 years of age.

With impaired renal function

The use of Zolerix is contraindicated for the treatment of patients with oncological pathologies in the presence of severe renal dysfunction (CC less than 30 ml / min).

The dose of Zolerix for mild and moderate renal impairment is prescribed taking into account the QC, which is determined before each infusion.

For violations of liver function

It is recommended to use Zolerix with caution in severe liver dysfunction; dose adjustment is not required.

Use in the elderly

When Zolerix is prescribed to patients over the age of 65, dose adjustment is not required.

Drug interactions

The simultaneous use of Zolerix with aminoglycosides, loop diuretics, calcitonin increases the risk of a more prolonged decrease in the level of calcium concentration in the blood plasma and the occurrence of hypocalcemia. Therefore, if necessary, this combination must be used with caution.

In case of impaired renal function, the combination of zoledronic acid with drugs that are excreted mainly by the kidneys can increase their systemic effect. With caution, it is necessary to use zoledronic acid with drugs that have a potentially nephrotoxic effect.

There is a risk of developing osteonecrosis of the lower jaw with joint therapy with angiogenesis inhibitors.

With the simultaneous use of Zoleriks with antitumor, antibacterial and / or analgesic agents, not loop diuretics, no clinically significant interaction has been established.

Combined therapy of multiple myeloma with zoledronic acid and thalidomide (in a daily dose of 100-200 mg) in patients with normal renal function does not significantly affect the pharmacokinetics of the drug and creatinine clearance. Dose adjustment of zoledronic acid may be required for mild to moderate renal impairment.

Analogs

Zoledronic acid, Zoledrex, Zolendronic-Rus 4, Aklasta, Zoledronate-Teva, Zometa, Rezorba, Blaztera, Veroclast, Rezoklastin are analogs of Zoledronic acid.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 30 ° C, do not freeze.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Zolerix

Reviews about Zolerix are rare. There are reports that the appearance of severe weakness, chills, dizziness, headache, shortness of breath after infusion of zoledronic acid is the reason for some patients to refuse repeated procedures. In those who continue drug therapy, despite the side effects, there is an improvement in their condition.

Price for Zolerix in pharmacies

The approximate price for Zolerix for a package containing 1 bottle of 5 ml concentrate can be 2200–3500 rubles, 1 bottle of concentrate of 6.25 ml - 8200–9900 rubles, 5 bottles of 5 ml concentrate - 3500–8200 rubles.

Zolerix: prices in online pharmacies

Drug name Price Pharmacy

Zolerix 0.8 mg / ml concentrate for preparation of solution for infusion 5 ml 1 pc. RUB 6138 Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!