Zolendronovaya acid | Zolerix vial, 4 mg

Release form

Concentrate for solution for infusion

Packaging

Bottle 5 ml.

Pharmacological action

Zoledronic acid is a highly effective bisphosphonate with a selective effect on bone tissue. The drug inhibits bone resorption by acting on osteoclasts. The selective effect of bisphosphonates on bone is due to their high affinity for mineralized bone, however, their exact molecular mechanism of action is still unclear. Zoledronic acid inhibits the activity of osteoclasts without exerting an undesirable effect on the formation, mineralization and mechanical properties of bone tissue.

In addition to the inhibitory effect on bone resorption, zoledronic acid has various antitumor properties that can contribute to the overall effect in the treatment of bone metastatic process. Preclinical studies have shown that zoledronic acid:

- In vivo: inhibits bone resorption by osteoclasts, changes the bone marrow microenvironment, and leads to a decrease in the growth of tumor cells and exhibits anti-angiogenic activity.

Suppression of bone resorption is clinically accompanied by a marked reduction in pain.

- In vitro: inhibits the proliferation of osteoblasts, exhibits direct cytostatic and proapoptotic activity, a synergistic cytostatic effect with antitumor drugs, anti-adhesive and anti-invasive activity.

In patients with prostate cancer and other solid tumors with metastatic bone damage, zoledronic acid prevents the development of pathological fractures, spinal cord compression, reduces the need for radiation therapy and surgical interventions, and reduces tumor hypercalcemia. The drug is able to inhibit the progression of pain. The therapeutic effect is less pronounced in patients with osteoblastic foci than with osteolytic ones.

In patients with tumor hypercalcemia, the effect of zoledronic acid is characterized by a decrease in serum calcium concentration and calcium excretion by the kidneys. The average time to normalize calcium concentration is about 4 days. By the 10th day, the concentration of calcium is normalized in 87-88% of patients. The average time to relapse (albumin-adjusted serum calcium concentration of at least 2.9 mmol / L) is 30-40 days. Significant differences between the effectiveness of zoledronic acid in doses of 4 and 8 mg in the treatment of hypercalcemia are not observed.

Contraindications

Hypersensitivity to zoledronic acid, other bisphosphonates or any other components,

component of the initial severe renal impairment (creatinine clearance 30 ml / min)

pregnancy and lactation period

for children and adolescents (safety and efficacy have not been studied).

With caution: When deciding on the use of zoledronic acid in patients with malignant hypercalcemia due to impaired renal function, it is necessary to assess the patient's condition and conclude whether the potential benefit of the drug is more likely to prevail. Caution should be observed when prescribing zoledronic acid to patients with bronchial asthma caused by acetylsalicylic acid (when using other bisphosphonates, there have been cases of bronchospasm).

Special instructions

Ensure that the patient is adequately hydrated before zoledronic acid infusion. If necessary, the introduction of a 0.9% sodium chloride solution is recommended before, in parallel, or after infusion of zoledronic acid. Overhydration of the patient should be avoided due to the risk of complications from the cardiovascular system.

After administration of zoledronic acid, constant monitoring of the concentration of calcium, phosphorus, magnesium and creatinine in the blood serum is necessary. With the development of hypocalcemia, hypophosphatemia or hypomagnesemia, there may be a need for a short additional administration of the appropriate substances. Patients with untreated hypercalcemia, as a rule, have impaired renal function, therefore, careful monitoring of renal function in this category of patients is necessary.

When deciding on the treatment of zoledronic acid in patients with bone metastases, it should be taken into account that the therapeutic effect occurs 2-3 months after the start of treatment with zoledronic acid.

There are some reports of impaired renal function with the use of bisphosphonates. Risk factors for the occurrence of such complications include dehydration, previous renal failure, repeated administration of zoledronic acid or other bisphosphonates, as well as the use of nephrotoxic drugs, and too rapid administration of the drug. Despite the fact that the risk of the above complications is reduced if zoledronic acid is administered at a dose of 4 mg for at least 15 minutes, the possibility of impaired renal function remains. Cases of impaired renal function, progression of renal failure, and the need for hemodialysis with the first or single use of zoledronic acid have been noted.

An increase in serum creatinine concentrations is also observed in some patients with prolonged use of zoledronic acid in recommended doses, although less frequently.

Since there is limited clinical data on the use of the drug in patients with severe hepatic impairment, it is not possible to give specific recommendations for this category of patients.

When deciding on the use of zoledronic acid in patients with hypercalcemia due to a malignant tumor, against the background of impaired renal function, it is necessary to assess the patient's condition and conclude whether the potential benefit of the drug is more likely to prevail.

Serum creatinine concentration should be determined before each administration of zoledronic acid. At the beginning of drug treatment for patients with bone metastases with impaired renal function of mild to moderate severity, it is recommended to use zoledronic acid in low doses. In patients in whom renal dysfunction appeared during therapy with zoledronic acid, drug therapy can be continued only after the serum creatinine concentration returns to values ​​that are within 10% of the initial value.

Cases of jaw osteonecrosis in cancer patients treated with bisphosphonates, including zoledronic acid, are described. Many patients had signs of a local infectious and inflammatory process, including osteomyelitis.

In clinical practice, the development of jaw osteonecrosis was most often observed in patients with advanced breast cancer and myeloma, as well as in the presence of dental diseases (after tooth extraction, periodontal disease, poor fixation of dentures). Known risk factors for jaw osteonecrosis are cancer, concomitant treatment (chemotherapy, radiation therapy, glucocorticosteroid treatment), concomitant diseases (anemia, coagulopathy, infection, previous oral disease).

Before prescribing bisphosphonates, patients should undergo a dental examination and perform the necessary preventive procedures, as well as recommend strict adherence to oral hygiene. During treatment of these patients, dental surgery should be avoided whenever possible. There is no evidence that interruption of treatment with bisphosphonates before dental interventions reduces the risk of osteonecrosis of the jaw. The treatment plan for a particular patient should be based on an individual assessment of the risk / benefit ratio.

In clinical practice, infrequent cases of the development of severe and, in some cases, disabling pain in bones, joints and muscles have been reported with the use of bisphosphonates, which include zoledronic acid. These symptoms developed over a period of one day to several months after the start of treatment. After discontinuation of treatment, the symptoms disappeared in most patients. In several patients, symptoms recurred when therapy was resumed or another bisphosphonate was prescribed.

The efficacy and safety of zoledronic acid in pediatric practice have not yet been established.

Composition of

In 1 ml of concentrate contains: active substance: zoledronic acid monohydrate (in terms of dry matter) - 0.8 mg

excipients: mannitol - 44 mg, sodium citrate dihydrate (in terms of sodium citrate) - 4, 8 mg, water for injection - up to 1 ml.

Side effects

Adverse reactions associated with the use of zoledronic acid, usually mild. Criteria for the frequency of adverse reactions: very often (? 1/10), often (? 1/100,

From the hemopoietic organs: often anemia, sometimes thrombocytopenia, leukopenia rarely pancytopenia.

From the nervous system: often - headache sometimes - dizziness, paresthesia, taste disturbances, hypesthesia, hyperesthesia, tremor, anxiety, sleep disturbance rarely - confusion.

From the side of the organ of vision: often - conjunctivitis sometimes - blurred vision, very rarely - uveitis, episcleritis.

From the digestive system: often - nausea, vomiting, anorexia, sometimes - diarrhea, constipation, abdominal pain, dyspepsia, stomatitis, dry mouth.

From the respiratory system: sometimes - shortness of breath, cough.

From the side of the skin and skin appendages: sometimes - itching, rash (including erythematous and macular), excessive sweating.

From the musculoskeletal system: often - bone pain, myalgia, arthralgia, generalized pain, sometimes - muscle cramps.

From the cardiovascular system: sometimes - a pronounced increase in blood pressure rarely - bradycardia.

From the urinary system: often - impaired renal function, sometimes - acute renal failure, hematuria, proteinuria.

On the part of the immune system: sometimes - allergic reactions rarely - angioedema.

Other: often - fever, flu-like condition (including chills, malaise, fever), sometimes - asthenia, peripheral edema, chest pain, weight gain.

Local reactions: pain, irritation, swelling, formation of infiltrate at the injection site.

On the part of laboratory indicators: very often - hypophosphatemia often - increased concentrations of creatinine and urea in the blood, sometimes hypocalcemia - hypomagnesemia, rarely - hyperkalemia, hypokalemia, hypernatremia.

During therapy with zoledronic acid, the following adverse events were observed in clinical practice, regardless of the presence of a causal relationship with the use of the drug:

In the treatment of patients with bisphosphonates, including zoledronic acid, cases of development of jaw osteonecrosis were sometimes noted (usually after extraction of a tooth or other dental intervention).

In very rare cases, with the use of zoledronic acid, a decrease in blood pressure was observed, leading to fainting or circulatory collapse, mainly in patients with risk factors, the development of drowsiness, bronchoconstriction and atrial fibrillation.

Drug Interactions

With the simultaneous use of other commonly used drugs (antitumor agents, diuretics, antibiotics, analgesics) with zoledronic acid, no clinically significant interactions were noted.

According to in vitro studies, zoledronic acid weakly binds to plasma proteins and does not inhibit isoenzymes of the P450 cytochrome system.

Caution is advised when using bisphosphonates and aminoglycosides at the same time, since the concomitant use of these drugs causes a more prolonged decrease in plasma calcium concentration.

Caution is necessary while using zoledronic acid with drugs that potentially have nephrotoxic effects.

In patients with multiple myeloma, an increased risk of developing renal dysfunction with the intravenous administration of bisphosphonates such as zoledronic acid in combination with thalidomide is possible.

Pharmaceutical interactions

The diluted zoledronic acid solution cannot be mixed with infusion solutions containing calcium ions (for example, Ringer's solution).

Overdose

Symptoms: Acute overdose of zoledronic acid (limited data) showed impaired renal function, including renal failure, changes in electrolyte composition, including the concentration of calcium, phosphates and magnesium in blood plasma.

Treatment: A patient who has received a dose exceeding the recommended dose should be monitored continuously. In the case of hypocalcemia, accompanied by clinical manifestations, Conducted infusion of calcium gluconate.

Storage conditions

Do not store above 30 РC.

Expiration

2 years.

Terms leave through pharmacies

In retseptu

dosage form

infusion solution