Zoleriks – an inhibitor of bone resorption, a bisphosphonate. It has a selective effect on bone. Has an inhibitory effect on bone resorption mediated by osteoclasts.
The selective action of bisphosphonates on bone is based on a high affinity for mineralized bone, but the precise molecular mechanism for the inhibition of osteoclastic activity is still unclear.
In addition to inhibitory effect on bone resorption, zolendronovaya acid has other antitumor properties providing therapeutic efficacy for bone metastases.
In vivo: inhibition of osteoclastic bone resorption modifying bone marrow microenvironment, leading to reduce tumor cell growth; antiangiogenic activity. Suppression of bone resorption is also accompanied by a clinically pronounced decrease in pain.
In vitro: Inhibition of osteoblast proliferation, direct cytotoxic and proapoptotic activity, synergistic cytostatic effect with anti-cancer drugs; anti-adhesive / invasive activity.
Zoledronic acid by inhibiting proliferation and inducing apoptosis, has direct anti-tumor effect against the human myeloma cells and cancerous breast tumors, and also reduces the penetration of tumor cells of breast cancer through the extracellular matrix that indicates the presence of Her antimetastatic properties. Also, zoledronic acid inhibits proliferation of human endothelial cells and in animals causes antiangiogenic effect.
Patients with hypercalcemia induced by tumor, it was shown that the effect of zoledronic acid is characterized by a decrease in calcium concentration in serum and decrease in its excretion in the urine.
After initiation of the infusion, serum concentrations increased rapidly, reaching a peak at the end of infusion, followed by a rapid decrease in concentration by 10% after 4 hours and to less than 1% – after 24 hours successively prolonged period of low concentrations not exceeding 0.1% of maximum to re-infusion on day 28.
Zoledronic acid introduced in / in, kidneys displayed in three phases: rapid biphasic elimination of the drug from the systemic circulation with a T1 / 2 0.24 h and 1.87 h and continuous phase with a finite T1 / 2 was 146 hr Not observed cumulation at. repeated administration every 28 days.
Zoledronic acid is not metabolised systemically and excreted by the kidneys unchanged. During the first 24 hours in the urine is detected 39 ± 16% of the administered dose. The remaining amount is mainly associated with the bone tissue. Then the reverse release of zoledronic acid are fast enough from the bone tissue into the systemic circulation and its excretion by the kidneys. Total plasma clearance was 5.04 ± 2.5 l / h. Increasing the infusion time from 5 to 15 min results in a decrease of zoledronic acid concentration of 30% at the end of infusion, but does not affect the AUC.
On feces output less than 3%.
The renal clearance of zoledronic acid was positively correlated with CC.
is shown zoledronic acid poor affinity to blood components. Binding to plasma proteins is low (about 50%) and does not depend on the concentration of zoledronic acid.
Active substance: zoledronic acid monohydrate (on dry basis) – 0.8 mg;
Excipients: Mannitol – 44 mg Sodium citrate dihydrate (calculated as sodium citrate) – 4.8 mg Water for injection – up to 1 ml
Osteolytic, and mixed osteoblastic bone metastasis of solid tumors and osteolytic lesions in multiple myeloma, in a combination therapy; hypercalcemia due to malignancy.
Pregnancy; lactation (breast feeding); hypersensitivity to zoledronic acid, other bisphosphonates.
From the side of hematopoiesis: rarely – thrombocytopenia, anemia, leucopenia; rarely – pancytopenia
Part of the central and peripheral nervous system: often – headache; sometimes – fatigue, paresthesia, dysgeusia, hypoesthesia, hyperesthesia, tremor
On the part of the psyche: sometimes – anxiety, sleep disorders; rarely – confusion
From a sight organ: common – conjunctivitis; sometimes – blurred vision
From the digestive system: often – nausea, vomiting, anorexia; sometimes – diarrhea, constipation, abdominal pain, dyspepsia, stomatitis, dry mouth
With the respiratory system: sometimes – dyspnoea, cough
Dermatological reactions: sometimes – itching, rash (including erythematous and macular), increased sweating
From the musculoskeletal system: often – bone pain, myalgia, arthralgia; sometimes – muscle cramps
Since the cardiovascular system: rarely – bradycardia
From the kidneys: often – impaired renal function; sometimes – acute renal failure, hematuria, proteinuria
Allergic reactions: sometimes – hypersensitivity reaction; rarely – angioedema
On the part of the body as a whole: often – fever, flu-like syndrome, which is manifested by fever, chills, bone pain and / or muscle; sometimes – asthenia, peripheral edema, chest pain, weight gain
Local reactions: sometimes – pain, irritation, swelling, and the formation of infiltration at the injection site
From the laboratory parameters: often – hypophosphatemia; often – increased creatinine and urea in serum, hypocalcemia; sometimes – hypomagnesemia; rarely – hyperkalemia, hypokalemia, hypernatremia
How to accept, acceptance rate and dosage
Enter intravenous infusion over 15 minutes. The recommended dosage is 4-8 mg. The frequency of administration depends on the indication, the treatment scheme employed, the therapeutic efficacy.
At a temperature of not higher than 30 ° C
In an application of bisphosphonates and aminoglycosides serum calcium levels may remain reduced over a long time than is required, because it is possible additive effects on serum calcium concentration.
While the use of drugs having potentially nephrotoxic effect increases the risk of deterioration of renal function.
Pregnancy and lactation
Zoleriks drug is contraindicated in pregnancy and lactation