Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Inhibitor of bone resorption, bisphosphonate. Has a selective effect on the bone. Has an inhibitory effect on bone resorption, mediated by osteoclasts.
Selective action of bisphosphonates on bone tissue is based on a high affinity for mineralized bone tissue, but the exact molecular mechanism providing inhibition of osteoclast activity is still unclear.
In addition to the inhibitory effect on the resorption of bone tissue, zolendronic acid has other antitumor properties that provide therapeutic efficacy in bone metastases.
In vivo: inhibition of osteoclastic bone resorption, altering 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 marked decrease in pain.
In vitro: inhibition of osteoblast proliferation, direct cytotoxic and pro-apoptotic activity, synergistic cytotoxic effect with antitumor drugs; anti-adhesive / invasive activity.
Zoledronic acid, suppressing 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 that it has antimetastatic properties. In addition, zoledronic acid inhibits the proliferation of human endothelial cells and in animals causes an anti-angiogenic effect.
In patients with hypercalcemia caused by a tumor, it was shown that the effect of zoledronic acid is characterized by a decrease in serum calcium concentration and a decrease in its excretion in the urine.
PHARMACOKINETICS
After the start of the infusion, the concentration of zoledronic acid in the plasma rapidly increases, reaching C max at the end of the infusion, followed by a rapid decrease in concentration by 10% after 4 hours and by less than 1% after 24 hours with a successively prolonged period of low concentrations not exceeding 0.1% from C max to repeated infusion on the 28th day.
Zoledronic acid, injected iv, is excreted by the kidneys in 3 stages: a rapid two-phase elimination from the system circulation with T 1/2 0.24 h and 1.87 h and a long phase with a finite T 1/2 of 146 h. No cumulation was observed with repeated administrations every 28 days.
Zoledronic acid is not subject to systemic metabolism and is excreted by the kidneys unchanged. During the first 24 hours, 39 В± 16% of the administered dose is detected in the urine. The remaining amount is mainly associated with bone tissue. Then slowly the reverse release of zoledronic acid from the bone tissue into the systemic blood flow and its excretion by the kidneys. The total plasma clearance is 5.04 В± 2.5 l / h. Increasing the infusion time from 5 to 15 minutes results in a 30% reduction in zoledronic acid at the end of the infusion, but does not affect the AUC.
With feces less than 3% is excreted.
Renal clearance of zoledronic acid positively correlates with QC.
Low affinity of zoledronic acid for blood components is shown. Binding to plasma proteins is low (about 50%) and does not depend on the concentration of zoledronic acid.
INDICATIONS
Osteolytic, osteoblastic and mixed bone metastases of solid tumors and osteolytic foci with multiple myeloma, as part of combination therapy; hypercalcemia caused by a malignant tumor.
DOSING MODE
Enter in / in the drip for 15 minutes. The recommended dose is 4-8 mg. The frequency of administration depends on the indications, the treatment regimen used, the therapeutic effectiveness.
SIDE EFFECT
From the hemopoietic system: infrequently - thrombocytopenia, anemia, leukopenia; rarely - pancytopenia.
From the nervous system: often - headache; infrequently - weakness, paresthesia, taste disorders, hypoesthesia, hyperesthesia, tremor, anxiety, sleep disorders; rarely confusion.
From the side of the organ of vision: often - conjunctivitis; infrequent - blurring of vision.
From the side of the digestive system: often - nausea, vomiting, anorexia; infrequently - diarrhea, constipation, abdominal pain, dyspepsia, stomatitis, dry mouth.
From the respiratory system: infrequently - dyspnoea, cough.
Dermatological reactions: infrequent - itching, rash (including erythematous and macular), increased sweating.
From the osteomuscular system: often - pain in the bones, myalgia, arthralgia; infrequently - muscle cramps.
From the cardiovascular system: rarely - bradycardia.
From the urinary system: often - a violation of kidney function; infrequently - acute renal failure, hematuria, proteinuria.
Allergic reactions: infrequently - reactions of increased sensitivity; rarely - angioedema.
From the side of metabolism: very often - hypophosphatemia; often - increasing the level of creatinine and urea in the blood serum, hypocalcemia; infrequently - hypomagnesemia, weight gain; rarely - hyperkalemia, hypokalemia, hypernatremia.
On the part of the body as a whole: often - fever, flu-like syndrome, manifested by fever, chills, pain in the bones and / or muscles; infrequently - asthenia, peripheral edema, pain in the chest.
CONTRAINDICATIONS
Pregnancy; lactation (breastfeeding); increased sensitivity to zoledronic acid, other bisphosphonates.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
It is not recommended for patients with severe renal dysfunction (serum creatinine concentration is 400 Ојmol / L or? 4.5 mg / dl), except when the expected benefit of therapy prevails over the potential risk.
There are some reports of a violation of kidney function against the background of bisphosphonates. The risk factors for such complications include previous renal failure and long-term use of zoledronic acid in high doses (8 mg), reduction in infusion time.
APPLICATION FOR CHILDREN
The effectiveness and safety of zoledronic acid in pediatric practice have not been established.
SPECIAL INSTRUCTIONS
At repeated application before each introduction it is necessary to define concentration of a creatinin in blood serum. If the findings indicate a worsening of kidney function, it is necessary to assess the risk and benefit of the therapy.
It is not recommended for patients with severe renal dysfunction (serum creatinine concentration is 400 Ојmol / L or? 4.5 mg / dl), except when the expected benefit of therapy prevails over the potential risk.
Before the infusion, dehydration in the patient should be avoided. To ensure adequate hydration, the administration of saline is recommended before, during or after the infusion of zoledronic acid. It is necessary to avoid hyperhydration of the patient because of the risk of complications from the cardiovascular system.
After the introduction of zoledronic, continuous monitoring of the concentration of calcium, phosphorus, magnesium and creatinine in the blood serum is necessary.
If hypocalcemia, hypophosphatemia, or hypomagnesemia develops, short-term maintenance therapy is needed.
There are some reports of a violation of kidney function against the background of bisphosphonates. The risk factors for such complications include previous renal failure and long-term use of zoledronic acid in high doses (8 mg), reduction in infusion time.
The effectiveness and safety of zoledronic acid in pediatric practice have not been established.
DRUG INTERACTION
With the simultaneous use of bisphosphonates and aminoglycosides, the serum calcium level may remain lowered longer than is required, since an additive effect on serum calcium concentration is possible.
With simultaneous use with drugs potentially having a nephrotoxic effect, the risk of impaired renal function increases.
