Zometa - Instructions For Use, Reviews, Analogues, Price

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

Zometa

Zometa: 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. Drug interactions
11. 11. Analogs
12. 12. Terms and conditions of storage
13. 13. Terms of dispensing from pharmacies
14. 14. Reviews
15. 15. Price in pharmacies

Latin name: Zometa

ATX code: M05BA08

Active ingredient: Zoledronic acid

Producer: Novartis Pharma Stein AG (Switzerland)

Description and photo update: 2019-07-08

Prices in pharmacies: from 8000 rubles.

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Zometa is an inhibitor of bone resorption in bone metastases.

Release form and composition

Dosage forms of Zometa:

• Concentrate for the preparation of solution for infusion: clear, colorless liquid (5 ml in plastic colorless bottles, 1 bottle in a cardboard box);
• Solution for infusion: colorless transparent liquid (100 ml in plastic bottles, 1 bottle in a cardboard box).

The active ingredient of Zometa is zoledronic acid:

• 1 bottle of concentrate - 4,264 mg of zoledronic acid monohydrate, which is equivalent to 4 mg of anhydrous zoledronic acid;
• 1 bottle of solution - 4 mg.

Auxiliary components:

• Concentrate: sodium citrate, mannitol, nitrogen, water for injection;
• Solution: mannitol, sodium citrate dihydrate, water for injection.

Pharmacological properties

Pharmacodynamics

Zoledronic acid, the active ingredient in Zometa, is a highly effective bisphosphonate that selectively affects bone tissue. The compound reduces bone resorption by acting on osteoclasts. The selective effect of bisphosphonates on bone tissue is explained by their high affinity for mineralized bone tissue. The exact mechanism of the process at the molecular level that provides inhibition of osteoclast activity remains unclear at the moment.

For zoledronic acid, adverse effects on bone formation, mineralization and mechanical properties are uncommon. The compound also has anti-tumor properties, making Zometa effective in the treatment of bone metastases. In vivo, the substance inhibits the resorption of bone tissue, for which osteoclasts are responsible, has antiangiogenic activity, helps to reduce the growth of tumor cells, and transforms the microenvironment of the bone marrow. A decrease in bone resorption is clinically expressed in a decrease in the intensity of pain in the patient.

In vitro, zoledronic acid is characterized by direct cytostatic, pro-apoptotic, anti-invasive and anti-adhesive activity, reduces the rate of osteoblast proliferation, and exhibits a synergistic cytostatic effect when used together with anticancer drugs.

Zoledronic acid, by suppressing proliferation and inducing apoptosis, has a direct antitumor effect on human breast cancer and myeloma cells. It also reduces the penetration of human breast cancer cells through the extracellular matrix due to its antimetastatic properties.

In oncological diseases with metastases affecting the bones, Zometa reduces the risk of fractures and compression of the spinal cord, and also prevents the development of tumor hypercalcemia and is an inhibitor of calcium excretion in the urine. This leads to a decrease in the need for radiation therapy.

Pharmacokinetics

Bisphosphonates are poorly absorbed in the gastrointestinal tract, so experts recommend using solutions for intravenous administration. The infusion causes an increase in the concentration of zoledronic acid in the blood serum, the maximum value of which is reached by the end of the infusion. After 4 hours, the level of the substance in the blood decreases by 10%, and after 24 hours - by another 1%.

Zoledronic acid binds to plasma proteins by 50%. It is excreted through the kidneys in stages, with a total elimination half-life of 146 hours. Repeated injections (after 28 days) do not cause a cumulative effect. On the first day, urine contains 40 ± 16% of the active component of Zometa from the entire administered dose. The rest of the zoledronic acid is deposited in the bone tissue and is gradually released into the systemic circulation. The compound is not metabolized and is excreted unchanged mainly through the kidneys (with feces - less than 3%).

Indications for use

• Bone metastases of malignant advanced tumors (breast cancer, prostate cancer), myeloma, including prevention of reducing the risk of spinal cord compression, pathological fractures, hypercalcemia associated with a tumor, and the need for bone surgery or radiation therapy;
• Hypercalcemia due to malignant neoplasm.

Contraindications

• The period of pregnancy and breastfeeding;
• Childhood;
• Hypersensitivity to bisphosphonates and drug components.

Zomet should be prescribed with caution in case of severe liver dysfunction.

The use of the drug for impaired renal function in patients with hypercalcemia caused by a malignant tumor is possible if the potential benefit of therapy outweighs the existing risk. It is not recommended to administer the drug to patients with severely impaired renal function: with a serum creatinine level of more than 265 μmol / L in patients with bone metastases, and more than 400 μmol / L in hypercalcemia caused by a malignant tumor.

Instructions for use of Zometa: method and dosage

The concentrate for the preparation of the solution for infusion and the solution for infusion are used by intravenous (IV) drip administration.

The dilution solution for the concentrate must be free of calcium! The solution for infusion is prepared in accordance with the rules of asepsis. Immediately before administration, the contents of 1 vial of the concentrate should be diluted in 100 ml of 0.9% sodium chloride solution or 5% dextrose solution. The unused solution can be stored for no more than 24 hours from the moment of preparation at a temperature of 2-8 ° C, and before administration it should be brought to room temperature after taking it out of the refrigerator.

According to the instructions, Zometa cannot be mixed with solutions containing calcium or any bivalent cations (Ringer's lactate solution) and with other drugs, therefore, a separate infusion system must be used to administer zoledronic acid solution.

Intravenous drip should last at least 15 minutes.

Recommended dosage:

• Bone metastases of common malignant tumors and myeloma: 4 mg 1 time in 3-4 weeks. The drug should be administered with the simultaneous ingestion of 500 mg of calcium and 400 international units (IU) of vitamin D per day;
• Hypercalcemia due to malignant tumor (calcium level corrected for albumin concentration more than 12 mg / dL or 3 mmol / L): 4 mg;
• Treatment of bone metastases in patients with mild or moderate renal impairment (creatinine clearance (CC) 30-60 ml / min): with CC: 30-39 ml / min - 3 mg, 40-49 ml / min - 3.3 mg, 50-60 ml / min - 3.5 mg of zoledronic acid.

Before the introduction of Zometa, in parallel or after it, the patient should be prescribed the introduction of saline to ensure adequate hydration.

Before each administration of the drug, the concentration of serum creatinine should be determined; in case of impaired renal function, the administration of the next dose should be postponed. Renal dysfunction parameters:

• Patients with normal (less than 1.4 mg / dl) baseline creatinine values - with an increase in serum creatinine concentration by 0.5 mg / dl;
• Patients with a baseline creatinine level of more than 1.4 mg / dL - with an increase in serum creatinine by 1 mg / dL.

Treatment can be resumed at the previous dose only after the creatinine concentration is restored to the initial (plus or minus 10%) level.

Side effects

• Hematopoietic organs: often - anemia; sometimes - leukopenia, thrombocytopenia; rarely - pancytopenia;
• Urinary system: often - renal dysfunction; sometimes - hematuria, acute renal failure, proteinuria;
• Nervous system: often - headache; sometimes - disturbances in taste, dizziness, hypoesthesia, paresthesia, hyperesthesia, sleep disorders, anxiety, tremor; rarely - confusion of consciousness;
• Digestive system: often - anorexia, nausea, vomiting; sometimes - dry mouth, abdominal pain, diarrhea, constipation, stomatitis, dyspepsia;
• Organ of vision: often - conjunctivitis; sometimes - "blurred" vision; very rarely - episcleritis, uveitis;
• Musculoskeletal system: often - myalgia, bone pain, generalized pain, arthralgia; sometimes - muscle cramps;
• Respiratory system: sometimes - cough, shortness of breath;
• Cardiovascular system: sometimes - a marked decrease or increase in blood pressure (BP); rarely - bradycardia;
• Immune system: sometimes - hypersensitivity reactions; rarely - angioedema;
• Dermatological reactions: sometimes - pruritus, excessive sweating, rash (including erythematous and macular);
• Laboratory indicators: very often - hypophosphatemia; often - hypocalcemia, increased concentration of creatinine and urea in the blood serum; sometimes - hypokalemia, hypomagnesemia; rarely - hypernatremia, hyperkalemia;
• Others: often - flu-like syndrome (chills, general malaise, fever, painful condition), fever; sometimes - chest pain, peripheral edema, asthenia, weight gain; very rarely - a decrease in blood pressure, causing fainting or circulatory collapse (mainly in patients with risk factors), bronchoconstriction, the development of drowsiness, atrial fibrillation, anaphylactic reactions or shock, urticaria;
• Local reactions: irritation, pain, swelling, at the injection site - the formation of an infiltrate.

Overdose

In acute overdose of Zometa, renal dysfunction, including renal failure, and changes in the electrolyte composition, including a decrease in the level of magnesium, calcium and phosphate in the blood, are observed.

If the recommended dose is significantly exceeded, the patient should remain under constant medical supervision. With the development of hypocalcemia, accompanied by clinical symptoms, an infusion of calcium gluconate is recommended.

special instructions

When Zometa is prescribed for impaired renal function in patients with hypercalcemia due to malignant neoplasm, the main criterion for assessing the feasibility of therapy is the excess of the benefits of using the drug over the potential risk.

Before each administration of the solution, it is required to determine the level of creatinine in the blood serum.

For bone metastases in patients with mild and moderate renal impairment, treatment should be started with lower doses. If a functional kidney disorder occurs during the treatment period, therapy can be continued only after recovery to the initial (plus / minus 10%) creatinine concentration level.

Due to the risk of complications from the cardiovascular system against the background of overhydration of the patient, administration of the drug should be started only after assessing the state of hydration of the body. In case of violations, the patient should be injected with saline before, during or after the infusion of the drug.

The use of Zometa must be accompanied by constant monitoring of the level of creatinine, phosphorus, calcium, magnesium in the blood serum. With the development of hypophosphatemia, hypocalcemia or hypomagnesemia, the patient is additionally prescribed the introduction of appropriate funds.

When administering the drug for the prevention of reducing the risk of spinal cord compression, pathological fractures, hypercalcemia caused by a tumor, reducing the need for bone surgery or radiation therapy, it should be borne in mind that the therapeutic effect occurs after 2-3 months of treatment.

Risk factors influencing the development of renal dysfunction include: previous renal failure, dehydration, repeated administration of bisphosphonates, the use of nephrotoxic agents, too rapid administration of Zometa's solution.

During the period of treatment, it is not recommended to carry out any dental manipulations, therefore, before prescribing the drug, the patient must undergo a dental examination, cure problem teeth and receive recommendations on the need for strict adherence to the rules of oral hygiene.

Cancer patients have a risk of osteomyelitis, infectious and inflammatory pathologies of the oral cavity, osteonecrosis of the jaw against the background of anticancer therapy.

Risk factors for osteonecrosis of the jaw include: cancer and concomitant treatment (use of corticosteroids, chemotherapy, radiation therapy), concomitant pathologies (including anemia, previous oral disease, coagulopathy, infections).

Against the background of the use of zoledronic acid, the development of severe transient pain in the joints, muscles and bones is possible.

The simultaneous use of Aklasta, the active ingredient of which is zoledronic acid, is contraindicated.

The influence of Zometa on the patient's ability to drive vehicles and mechanisms has not been established.

Application during pregnancy and lactation

The appointment of Zometa during pregnancy is prohibited. The drug can negatively affect the fetus. Studies carried out on animals have revealed a toxic effect on the reproductive function of the latter. There is no reliable information on the use of Zometa during pregnancy in humans.

Conception while on bisphosphonate treatment increases the risk of fetal abnormalities (eg, skeletal growth disorders and other malformations). The relationship between the risk and the amount of time elapsed between the cancellation of Zometa and fertilization is unknown. Patients of reproductive age should be warned about the need to use reliable contraceptive methods throughout treatment.

It is not known whether the active ingredient of Zometa penetrates into breast milk, therefore, the administration of the drug is contraindicated during lactation.

Drug interactions

There was no clinically significant interaction when Zometa was combined with anticancer drugs, diuretics, antibiotics, analgesics and other anticancer therapy.

It was found that zoledronic acid does not inhibit the enzymes of the cytochrome P _{450 system} and does not have significant binding to plasma proteins.

Caution should be exercised when used in combination with aminoglycosides (because due to the simultaneous action of drugs, the risk of an increase in the level of calcium concentration in the blood plasma increases) and drugs with a pronounced nephrotoxic effect.

In multiple myeloma, the combination with thalidomide increases the risk of renal dysfunction.

The drug is pharmaceutically incompatible with infusion calcium-containing solutions, including Ringer's solution.

For the introduction of Zometa, it is allowed to use glass vials, infusion systems, polyvinyl chloride, polyethylene and polypropylene bags with 0.9% sodium chloride solution or 5% dextrose solution.

Analogs

The analogues of Zometa are: Rezoscan, Zolendronic-Rus 4, Aklasta, Blaztera, Zoledronic acid, Zolerix, Zoledrex, Zoledronate-Teva, Rezoklastin FS, Rezorba, Veroclast.

Terms and conditions of storage

Store at temperatures up to 30 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Zometa

Despite the high cost, reviews of Zometa confirm the effectiveness of the drug. Today, zoledronic acid is considered a bisphosphonate with the most powerful effect on the body, therefore the drug is often prescribed for osteoporosis in the postmenopausal period.

When using Zometa throughout the year (1 mg 4 times a year, 2 mg 2 times a year or 4 mg once), an increase in the density of the femoral neck and lumbar vertebrae is observed. It is also suitable for the treatment of secondary osteoporosis caused by a metastatic process.

Clinical trials have confirmed the effectiveness of the drug in the treatment of cancer, therefore it is widely used in the practice of oncologists. Experts believe that inhibition of bone resorption can positively affect the progression of cancer in general and prolong the period of remission of breast cancer after surgery or radiation therapy.

Quite often, patients note the presence of side effects associated with taking Zometa. IV zoledronic acid for the first time may cause fever, malaise, muscle pain, and flu-like symptoms, but these symptoms disappear with subsequent infusions. In this case, the pain sensations decrease, and the calcium level is normalized.

In isolated cases, after a recent tooth extraction, the patient had osteonecrosis of the jaw.

The price of Zomet in pharmacies

You can buy a bottle of concentrate for the preparation of a solution for infusion of 4 mg / 5 ml in pharmacies for about 10,700-12,000 rubles. The price of Zometa in the form of a solution for infusion of 4 mg / 100 ml is on average 11,900-13,500 rubles (per bottle).

Zometa: prices in online pharmacies

Drug name Price Pharmacy

Zometa 4 mg / 5 ml concentrate for preparation of solution for infusion 5 ml 1 pc. RUB 8,000 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!