Rezoklastin, 1 piece, 6.25 ml, 5 mg/6.25 ml, concentrate for solution for infusion

Rezoklastin, 1 piece, 6.25 ml, 5 mg/6.25 ml, concentrate for solution for infusion

The drug Rezoklastin belongs to a new class of highly effective bisphosphonates that have a selective effect on bone tissue. Zoledronic acid inhibits the activity of osteoclasts and does not have undesirable effects on the formation, mineralization and mechanical properties of bone tissue. The selective action of bisphosphonates on bone tissue is based on their high affinity for mineralized bone tissue, but the exact molecular mechanism that provides inhibition of osteoclast activity remains unclear. Zoledronic acid, in addition to its inhibitory effect on bone resorption, has direct antitumor properties that ensure effectiveness in bone metastases.

In vitro, it was found that zoledronic acid, by suppressing proliferation and inducing cell apoptosis, has a direct antitumor effect on myeloma and breast cancer cells and reduces the risk of their metastasis. Inhibition of osteoclastic bone resorption leads to a decrease in tumor cell growth; antiangiogenic and analgesic activity is noted. Zoledronic acid also inhibits the proliferation of human endothelial cells. With hypercalcemia caused by a tumor, it reduces the concentration of calcium in the blood serum.

When using zoledronic acid in patients with postmenopausal osteoporosis (T-criterion values ​​for femoral neck bone mineral density less than -2.5), there was a statistically significant reduction in the risk of vertebral fractures, as well as a reduction in the risk of developing one or more new (recurrent) vertebral fractures.

When treated with zoledronic acid in patients with Paget's disease of bone, a statistically significant, rapid and long-term therapeutic response was observed, as well as normalization of the level of bone turnover and the concentration of alkaline phosphatase in the blood plasma.

The drug is also highly effective in patients previously treated with oral bisphosphonates. It has been established that in the majority of patients using zoledronic acid, the therapeutic response persists throughout the entire treatment period (about 2 years).

In patients with postmenopausal osteoporosis and Paget's disease of bone, zoledronic acid does not affect the qualitative state of normal bone, does not disrupt the processes of bone remodeling and mineralization, and promotes the preservation of normal trabecular bone architecture.

Rezoklastin FS

Rezoklastin FS

administered intravenously, over a period of at least 15 minutes.

For hypercalcemia caused by malignant tumors

(albumin-corrected calcium concentration >12 mg/dL or 3 mmol/L), the recommended dose of the drug is 4 mg, once. The infusion is carried out provided that the patient is adequately hydrated.

For metastatic bone lesions in malignant solid tumors and multiple myeloma

The recommended dose of the drug is 4 mg every 3-4 weeks. Additionally, it is recommended to prescribe oral calcium at a dose of 500 mg per day and vitamin D at a dose of 400 IU per day.

For postmenopausal and senile forms of primary osteoporosis

in order to increase bone mineral density, prevent fractures of vertebral bodies and other skeletal bones, the recommended dose of
Rezoklastin FS
is 5 mg, once a year.

For secondary osteoporosis

The recommended dose of
Rezoklastin FS
is 5 mg, once a year. If the intake of calcium and vitamin D from food is insufficient, patients with osteoporosis should be additionally prescribed calcium and vitamin D supplements. The duration of use of the drug is determined by the doctor individually depending on the patient’s condition.

For the treatment of Paget's disease of bone

A single intravenous administration of the drug at a dose of 5 mg is recommended. Since Paget's disease of bone is characterized by a high level of bone turnover, it is recommended that all patients with this disease take a daily dose of calcium and vitamin D for the first 10 days after administration of zoledronic acid.

Repeated treatment of Paget's disease of bone with zoledronic acid.

After the first administration of the drug, a long period of remission is observed. Currently, there are no specific data on re-treatment of Paget's disease of bone. However, the possibility of repeated administration of the drug can be considered if a relapse of the disease is detected in patients based on the following criteria: lack of normalization of serum alkaline phosphatase activity, an increase in its activity over time, as well as the presence of clinical signs of Paget’s bone disease, detected during a medical examination after 12 months after the first dose of zoledronic acid.

In patients with impaired renal function

Hypercalcemia due to malignant tumors:

The decision to treat patients with severe renal impairment with zoledronic acid should only be made after a careful assessment of the risk/benefit ratio. If the serum creatinine concentration is <400 µmol/L or <4.5 mg/dL, no dosage adjustment is required.

Metastatic bone lesions in malignant solid tumors and multiple myeloma:

The dose of zoledronic acid in patients with impaired renal function depends on the initial level of creatinine clearance (CC), calculated using the Cockcroft-Gault formula. In case of severe renal impairment (creatinine clearance <30 ml/min), the use of zoledronic acid is not recommended. Recommended doses for mild or moderate renal impairment (creatinine clearance values ​​30-60 ml/min) are given below.

Serum creatinine concentrations should be determined before each dose of the drug. If renal dysfunction is detected, the next administration of zoledronic acid should be postponed. Renal dysfunction is determined by the following parameters:

• for patients with normal initial creatinine values
  ​​(<1.4 mg/dl) - an increase in serum creatinine by 0.5 mg/dl;
• for patients with deviations in baseline creatinine levels
  (>1.4 mg/dL) - an increase in serum creatinine concentration by 1 mg/dL.

Therapy with zoledronic acid is resumed only after the creatinine concentration reaches values ​​exceeding the initial value by no more than 10%, at the same dose that was used before interruption of treatment.

Instructions for preparing the solution

The solution is prepared under aseptic conditions. Before administration, the drug is diluted (the contents of 1 bottle is 4 mg / -5 ml or 5 mg / 6.25 ml, depending on the recommended dose) in 100 ml of solution for infusion that does not contain calcium (0.9 %

sodium chloride solution or 5
%
dextrose solution). It is advisable to use the prepared solution of Rezoklastin FS immediately after preparation. Unused solution can be stored in the refrigerator at a temperature of 2 to 8 ° C for no more than 24 hours. Before administration, the solution should be kept indoors until it reaches room temperature. The prepared zoledronic acid solution must be administered using a separate IV infusion system.

Rezoclastin conc for preparation of solution inf 4mg/5ml

Active substance.

Zoledronic acid

Dosage form.

Concentrate for the preparation of solution for infusion.

Compound.

1 ml of concentrate contains: active substance: Zoledronic acid monohydrate - 0.85 mg (corresponds to anhydrous zoledronic acid) 0.80 mg; excipients: D-Mannitol - 44.0 mg, Sodium citrate dihydrate - 5.5 mg (corresponding to anhydrous sodium citrate) 4.8 mg, Water for injection up to 1.0 ml

1 bottle contains 5 ml (4 mg of zoledronic acid) or 6.25 ml (5 mg of zoledronic acid) concentrate.

Description.

The drug "Rezoklastin FS" belongs to a new class of highly effective bisphosphonates that have a selective effect on bone tissue. Zoledronic acid inhibits the activity of osteoclasts and does not have undesirable effects on the formation, mineralization and mechanical properties of bone tissue. The selective action of bisphosphonates on bone tissue is based on their high affinity for mineralized bone tissue, but the exact molecular mechanism that provides inhibition of osteoclast activity remains unclear. Zoledronic acid, in addition to its inhibitory effect on bone resorption, has direct antitumor properties that ensure effectiveness in bone metastases.

In vitro, it was found that zoledronic acid, by suppressing proliferation and inducing cell apoptosis, has a direct antitumor effect on myeloma and breast cancer cells and reduces the risk of their metastasis. Inhibition of osteoclastic bone resorption leads to a decrease in tumor cell growth; antiangiogenic and analgesic activity is noted. Zoledronic acid also inhibits the proliferation of human endothelial cells. With hypercalcemia caused by a tumor, it reduces the concentration of calcium in the blood serum.

When using zoledronic acid in patients with postmenopausal osteoporosis (T-criterion values ​​for femoral neck bone mineral density less than 2.5), there was a statistically significant reduction in the risk of vertebral fractures, as well as a reduction in the risk of developing one or more new (recurrent) vertebral fractures. When treated with zoledronic acid in patients with Paget's disease of bone, a statistically significant, rapid and long-term therapeutic response, normalization of the level of bone turnover and the concentration of alkaline phosphatase in the blood plasma were observed.

The drug is also highly effective in patients previously treated with oral bisphosphonates. It has been established that in the majority of patients using zoledronic acid, the therapeutic response persists throughout the entire treatment period (about 2 years).

In patients with postmenopausal osteoporosis and Paget's disease of bone, zoledronic acid does not affect the qualitative state of normal bone, does not disrupt the processes of bone remodeling and mineralization, and promotes the preservation of normal trabecular bone architecture.

Indications.

• Hypercalcemia (albumin-corrected serum calcium concentration >12 mg/dL or 3 mmol/L) induced by malignant tumors.
• Metastatic bone disease from malignant solid tumors and myeloma (to reduce the risk of pathological fractures, spinal cord compression, tumor-related hypercalcemia, and reduce the need for radiation therapy).
• Postmenopausal form of primary osteoporosis.
• Senile form of primary osteoporosis.
• Secondary osteoporosis.
• Paget's disease of bone.

Content

• Characteristics of rezoclastin (concentrated solution for inf. 5 mg/6.25 ml bottle No. 1)

Composition: 1 ml of solution contains: zoledronic acid 800 mcg.

Pharmacological action: Bone resorption inhibitor, bisphosphonate.

Has a selective effect on bone.

It has an inhibitory effect on bone resorption mediated by osteoclasts.

The selective effect of bisphosphonates on bone tissue is based on a high affinity for mineralized bone tissue, but the exact molecular mechanism that provides inhibition of osteoclast activity remains unclear.

In addition to its inhibitory effect on bone resorption, zoledronic acid has other antitumor properties that provide therapeutic efficacy in bone metastases.

In vivo: inhibition of osteoclastic bone resorption, changing the microenvironment of the bone marrow, leading to a decrease in the growth of tumor cells; antiangiogenic activity.

Suppression of bone resorption is clinically accompanied by a pronounced decrease in pain.

In vitro: inhibition of osteoblast proliferation, direct cytotoxic and proapoptotic activity, synergistic cytostatic effect with antitumor drugs; anti-adhesive/invasive activity.

Zoledronic acid, by inhibiting proliferation and inducing apoptosis, has a direct antitumor effect against human myeloma cells and breast cancer, and also reduces the penetration of breast cancer cells through the extracellular matrix, which indicates the presence of antimetastatic properties.

In addition, zoledronic acid inhibits the proliferation of human endothelial cells and causes an antiangiogenic effect in animals.

In patients with tumor-induced hypercalcemia, zoledronic acid has been shown to act by decreasing serum calcium concentrations and decreasing urinary calcium excretion.

Indications for Use: Osteolytic, osteoblastic and mixed bone metastases of solid tumors and osteolytic lesions in multiple myeloma, as part of combination therapy; hypercalcemia caused by a malignant tumor.

Method of Administration: Administer intravenously over 15 minutes.

The recommended dose is 4-8 mg.

The frequency of administration depends on the indications, the treatment regimen used, and therapeutic effectiveness.

Interaction: When bisphosphonates and aminoglycosides are used concomitantly, serum calcium levels may remain depressed for longer than required because additive effects on serum calcium concentrations are possible.

When used simultaneously with drugs that potentially have nephrotoxic effects, the risk of deterioration of renal function increases.

Side Effects: From the hematopoietic system: infrequently - thrombocytopenia, anemia, leukopenia; rarely - pancytopenia.

From the nervous system: often - headache; infrequently - weakness, paresthesia, disturbance of taste, hypoesthesia, hyperesthesia, tremor, anxiety, sleep disorders; rarely - confusion.

From the organ of vision: often - conjunctivitis; infrequently - blurred vision.

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

From the respiratory system: infrequently - dyspnea, cough.

Dermatological reactions: uncommon - itching, rash (including erythematous and macular), increased sweating.

From the musculoskeletal system: often - bone pain, myalgia, arthralgia; infrequently - muscle cramps.

From the cardiovascular system: rarely - bradycardia.

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

Allergic reactions: infrequently - hypersensitivity reactions; rarely - angioedema.

From the side of metabolism: very often - hypophosphatemia; often - increased levels of creatinine and urea in the blood serum, hypocalcemia; uncommon - hypomagnesemia, weight gain; rarely - hyperkalemia, hypokalemia, hypernatremia.

From the body as a whole: often - fever, flu-like syndrome, manifested by fever, chills, pain in the bones and/or muscles; uncommon - asthenia, peripheral edema, chest pain.

Contraindications: Pregnancy; lactation (breastfeeding); hypersensitivity to zoledronic acid and other bisphosphonates.

Special Instructions: When repeated use, the concentration of creatinine in the blood serum should be determined before each administration.

If the data obtained indicate a deterioration in renal function, it is necessary to evaluate the risks and benefits of the therapy.

It is not recommended for use in patients with severely impaired renal function (serum creatinine concentration ≥400 µmol/l or ≥4.

5 mg/dL) unless the expected benefit of therapy outweighs the potential risk.

Before infusion, the patient should be excluded from dehydration.

To ensure adequate hydration, administration of saline before, during, or after the zoledronic acid infusion is recommended.

Overhydration of the patient should be avoided due to the risk of cardiovascular complications.

After administration of zoledronova, constant monitoring of the concentrations of calcium, phosphorus, magnesium and creatinine in the blood serum is necessary.

If hypocalcemia, hypophosphatemia, or hypomagnesemia develops, short-term maintenance therapy is necessary.

There are isolated reports of renal dysfunction associated with the use of bisphosphonates.

Risk factors for the development of such complications include previous renal failure and long-term use of zoledronic acid in high doses (8 mg), reducing infusion time.

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