Zometa

Zometa slows down bone resorption processes and corrects metabolic processes in bone tissue.

Indications Zometa

It is used in case of such violations:

• secondary bone tissue damage (metastases) in tumors of a widespread nature (prostate or breast carcinoma);
• multiple myeloma;
• hypercalcemia of tumor origin or hyperparathyroidism;
• prevention of the occurrence of pathological fractures;
• prevention of spinal cord compression;
• in surgical procedures involving bones;
• prevention of osteoporosis during therapy for breast carcinoma using aromatase inhibitors.

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Release form

The substance is released in the form of an infusion liquid, in vials with a capacity of 4 mg/0.1 l, and also in the form of a concentrate in vials with a capacity of 4 mg/5 ml.

Pharmacodynamics

Zoledronic acid is a bisphosphonate with high therapeutic efficacy. It inhibits bone resorption by affecting osteoclasts that destroy bone tissue.

The selective effect on bone tissues is associated with a significant affinity for them. Osteoclasts absorb bisphosphonates exclusively in areas of bone change, and then the effect on bone tissues slows down, and the process of their destruction stops. But individual details of the principle of the drug's effect have not yet been finally determined.

The drug has a powerful anti-resorption effect. Use in women with osteoporosis associated with postmenopause led to a reliable decrease in the likelihood of vertebral fractures and their recurrence. During therapy in people with Paget's disease, a reliable and long-term therapeutic response is noted, stabilization of alkaline phosphatase indicators and bone metabolism values. In people with such pathologies, the drug does not affect the condition of healthy bone, helps to preserve its architecture and does not destroy mineralization.

At the same time, the drug, by inhibiting cell proliferation, causes an antitumor effect in the case of myeloma or breast tumor. It has antimetastatic activity, due to which it can be used for bone metastases, as well as for their prevention. Slowing down bone resorption significantly reduces pain.

In the case of carcinoma with metastases affecting the bones, the drug prevents the occurrence of fractures, as well as spinal cord compression, reduces tumor-related hypercalcemia and urinary Ca excretion. The need for radiation therapy is often reduced.

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Pharmacokinetics

Bisphosphonates have poor absorption in the gastrointestinal tract, which is why it is more advisable to use a medicinal liquid for intravenous injections. Infusion increases the indicators in the serum and they reach a maximum by its end. After 4 hours, a decrease in values by 10% is noted, and then by another 1% after the next 24 hours. Intraplasmic protein synthesis is 50%.

The drug is excreted through the kidneys in several phases; the final half-life is 146 hours. In the case of repeated injections (after a 28-day interval), the drug does not accumulate. During the first day, approximately 40±16% of the dose is recorded in the urine. The remainder is deposited in bone tissue, after which it is released into the circulatory system at a low rate. The substance does not participate in metabolic processes, excreting through the kidneys unchanged (less than 3% is excreted with feces).

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Dosing and administration

The medicinal concentrate (4 mg/5 ml) is dissolved in dextrose solution or NaCl (0.1 l). The finished substance should be used immediately. The infusion procedure lasts 15 minutes. The finished liquid can be stored for 24 hours at a temperature of 2-8°C. It is prohibited to mix the medicine with other agents, and its administration should be performed through a separate infusion system.

In case of bone metastases in tumors of a widespread nature and myelomas, 4 mg of the drug is used 1 time over a 3-4 week period.

To prevent osteoporosis with pathological fractures due to breast carcinoma during therapy with aromatase inhibitors during postmenopause, 4 mg of the drug should be used once every six months.

It is important to take into account that during therapy, blood urea, creatinine and mineral values should be monitored regularly. Creatinine values are checked before each injection.

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Use Zometa during pregnancy

It is prohibited to prescribe to pregnant or lactating women.

Contraindications

Main contraindications:

• severe sensitivity to bisphosphonates, as well as zoledronic acid;
• severe renal failure (CC values ≤30 ml/minute).

Caution is required when used in individuals with renal impairment, liver failure, and aspirin-type bronchial asthma.

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Side effects Zometa

Often, when using the medication, the following side effects are noted:

• flu-like syndrome and fever, as well as headaches;
• anemia;
• conjunctivitis;
• loss of appetite, vomiting with nausea;
• pain in the area of joints and bones;
• renal dysfunction;
• hypocalcemia or hypophosphatemia, as well as an increase in the values of urea and creatinine.

Occasionally the following symptoms appear:

• feelings of confusion or anxiety, dizziness, sleep disturbances, and tremors;
• pancyto- or leukopenia;
• uveitis or blurred vision;
• stomatitis, constipation, pain in the abdominal area, diarrhea and dryness affecting the oral mucosa;
• cough or dyspnea;
• rashes and itching;
• cramps affecting muscles;
• decrease or increase in blood pressure, as well as bradycardia;
• proteinuria or hematuria, and in addition, acute renal failure;
• swelling, asthenia and weight gain;
• hypokalemia or -magnesemia, as well as hypernatremia.

Urticaria, anaphylaxis, bronchial spasm, drowsiness and atrial fibrillation were recorded in isolated cases.

Overdose

In acute poisoning with Zometa, kidney function is disrupted (even acute renal failure may occur), and in addition, the electrolyte structure of the blood changes (calcium with phosphates and magnesium).

In case of development of clinically significant hypocalcemia, it is necessary to perform infusions with the introduction of calcium gluconate.

Interactions with other drugs

The combination of the drug with aminoglycosides increases the likelihood of hypocalcemia.

It is prohibited to combine the drug with agents that have a nephrotoxic effect.

The combination of drugs with thalidomide increases the likelihood of developing renal dysfunction and acute renal failure in individuals with multiple myeloma.

Zometa is not chemically compatible with Ringer's solution.

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Storage conditions

Zometa should be stored at temperatures not exceeding 30°C.

Shelf life

Zometa can be used within a 3-year period from the date of manufacture of the drug.

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Application for children

Zometa should not be used in pediatrics.

Analogues

Analogues of the substance are the drugs Rezoscan, Zoledrex, Blastera and Zoledronic-Rus 4, as well as Zolerix, Aclasta, Veroclast with Zoledronic acid, Resorba with Rezoklastin FS and Zoledronate-Teva.

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Reviews

Zometa is often commented on for the negative symptoms it causes. Intravenous bisphosphonates have been associated with muscle pain, fever, flu-like symptoms, and general malaise with the first injection, but these have not occurred with subsequent injections.

Reviews also mention a single development of jaw osteonecrosis with recent tooth extractions in individuals who received high doses of bisphosphonates through infusion.