Rezorba
Rezorba: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Rezorba
ATX code: M05BA08
Active ingredient: triamcinolone acetonide (triamcinolone acetonide)
Producer: JSC "Pharm-Sintez", LLC "Diamed", LLC "Company" DEKO "(Russia)
Description and photo updated: 20.11.2018
Prices in pharmacies: from 4734 rubles.
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Resorba is a bisphosphonate that inhibits bone resorption.
Release form and composition
Resorba is produced in the form of a lyophilisate for preparing a solution for infusion: a porous mass (powder) of almost white or white color [4 mg each in dark glass vials with a capacity of 10 ml, in a blister strip packaging 1 bottle complete with 1 ampoule of solvent (water for injection - 5 ml), in a cardboard box 1 package complete with 1 container (100 ml) of solvent - sodium chloride 0.9% solution for infusion or without it].
1 bottle contains:
- active substance: zoledronic acid monohydrate - 4.26 mg, which is equivalent to the content of 4 mg of anhydrous zoledronic acid;
- auxiliary components: sodium citrate dihydrate, D-mannitol.
Solvents - colorless, odorless transparent liquids: in an ampoule - water for injection (5 ml), in a container - 0.9% sodium chloride solution for infusion (100 ml).
Pharmacological properties
Pharmacodynamics
Zoledronic acid is a highly effective bisphosphonate that has a selective effect on bone tissue, inhibiting its resorption and affecting osteoclasts. The selectivity of the action of bisphosphonates on bone tissue is due to their high similarity with mineralized bone tissue. The mechanism by which osteoclast activity is inhibited at the molecular level has not been established.
Zoledronic acid does not have undesirable effects on bone mechanical properties, mineralization or formation.
Resorba has antitumor properties, their effectiveness is used in the treatment of bone metastases. The results of in vivo studies confirm the inhibitory effect of the drug on bone resorption by osteoclasts, changes in the microenvironment of the bone marrow, a decrease in the growth of tumor cells, and the manifestation of the antiangiogenic activity of bisphosphonate. Suppression of bone resorption is accompanied by a marked decrease in pain and other clinical signs.
In vitro zoledronic acid inhibits the proliferation of osteoblasts, has a direct proapoptotic and cytostatic effect, exhibits antiadhesive and anti-invasive activity. The synergism of antitumor activity with other cytostatics allows, when zoledronic acid is combined with chemotherapy or hormonal therapy, to suppress proliferation and induce apoptosis, to exert an antitumor effect directly against breast cancer and human myeloma cells. The antimetastatic properties of the active substance are confirmed by a decrease in the number of human breast cancer cells penetrating through the extracellular matrix. Zoledronic acid has an antiangiogenic effect, inhibits the proliferation of mammalian endothelial cells.
In the treatment of solid tumors with metastatic bone lesions, including breast and prostate cancer, zoledronic acid helps prevent the development of pathological fractures in patients, compression of the spinal cord, decrease tumor hypercalcemia, and reduce the need for surgical interventions and radiation therapy. Resorba inhibits the progression of pain syndrome. The therapeutic effect of the drug is more pronounced in patients with osteolytic foci than with osteoblastic ones.
In multiple myeloma and breast cancer with at least one bone focus, the effectiveness of using zoledronic acid at a dose of 4 mg corresponds to the action of pamidronic acid at a dose of 90 mg.
With tumor hypercalcemia, the action of Resorba promotes the excretion of calcium by the kidneys and a decrease in the level of calcium in the blood serum. Normalization of calcium levels occurs on average after 4 days, in 87–88% of patients - by the 10th day. The period before relapse (serum calcium level, corrected for albumin, not less than 2.9 mmol / l) is on average 30-40 days.
Studies have shown that in the treatment of bone metastases and hypercalcemia, the frequency and severity of adverse effects observed in patients with the use of zoledronic acid (4 and 8 mg), pamidronic acid (90 mg) or placebo is comparable.
Pharmacokinetics
Absorption and distribution of Resorba are independent of dose. The serum zoledronic acid level rapidly increases after the start of the infusion and reaches the maximum concentration (Cmax) in the blood by the end of the infusion. Then comes a period of rapid decrease in its concentration. After 4 hours, the level decreases by 10%, after 24 hours - by less than 1% of Cmax, during the period before repeated infusion, the concentration level does not exceed 0.1% of Cmax.
Plasma protein binding is about 56%.
Zoledronic acid is not metabolized and is excreted unchanged through the kidneys.
Removal occurs in 3 stages. Two phases T1 / 2 (half-life) from the systemic circulation are 0.24 hours and 1.87 hours, the third phase is 146 hours. With repeated administration every 28 days, no accumulation of the drug was noted.
In the urine during the first 24 hours, up to 39% of the administered dose is found, the rest of the drug binds to the bone tissue, followed by slow release into the systemic circulation. The total plasma clearance of the drug does not depend on the dose, age, sex, weight or race of the patient and is 5.04–2.5 l / h. An increase in the duration of the infusion from 5 to 15 minutes causes a 30% decrease in the concentration of zoledronic acid at the end of the infusion, but does not affect its total plasma concentration (AUC).
Less than 3% of the administered dose of Resorba is excreted through the intestines.
In humans, zoledronic acid does not inhibit cytochrome P450 isozymes and does not undergo biotransformation. Since pharmacokinetic studies in patients with liver failure and hypercalcemia have not been carried out, the assumption that there is no significant effect of liver function on the pharmacokinetics of zoledronic acid is based on in vitro results.
Renal clearance of zoledronic acid positively correlates with creatinine clearance (CC). With severe renal failure (CC less than 20 ml / min), the calculated clearance of zoledronic acid from the zoledronate clearance indicators in patients with CC more than 84 ml / min is 37%, with moderate renal failure (CC 20-50 ml / min) it corresponds to 72% …
Indications for use
- myeloma and metastatic bone lesions against the background of malignant solid tumors - to reduce the risk of tumor-related hypercalcemia, pathological fractures, spinal cord compression, and reduce the need for radiation therapy;
- hypercalcemia (concentration of serum calcium corrected for albumin, 3 mmol / L or 12 mg / dL and above) caused by malignant tumors.
Contraindications
- severe renal failure, CC less than 30 ml / min;
- period of pregnancy;
- breast-feeding;
- children and adolescence;
- established hypersensitivity to other bisphosphonates;
- individual intolerance to the components of the drug.
Care must be taken when prescribing Resorba to patients with impaired renal function, bronchial asthma (with increased sensitivity to acetylsalicylic acid), severe hepatic failure.
Instructions for use of Resorba: method and dosage
The finished solution is used by drip IV injection.
The solution for infusion is prepared under aseptic conditions before direct administration.
To dissolve the lyophilisate, 5 ml of water for injection should be added to the contents of the vial (4 mg), then it should be gently shaken to completely dissolve. The resulting solution is required to be diluted in 100 ml of 0.9% sodium chloride solution or 5% dextrose solution.
Do not use solutions containing calcium!
If necessary, the prepared solution can be stored in the refrigerator for no more than 24 hours at a temperature of 2–8 ° C. The ready-made solution for infusion stored in the refrigerator should be pre-warmed to room temperature.
The duration of the infusion should be at least 15 minutes.
Recommended dosage of Resorba:
- bone metastases, osteolytic foci in multiple myeloma: 4 mg with an interval of 21-28 days. Treatment is accompanied by the additional appointment of daily intake of calcium in a dose of 500 mg and vitamin D - 400 IU;
- hypercalcemia caused by malignant tumors: a single dose of 4 mg.
Infusion can only be performed if the patient is adequately hydrated.
It is not recommended to use Resorba in severely impaired renal function with CC less than 30 ml / min.
In patients with hypercalcemia caused by malignant tumors, with impaired renal function with a serum creatinine concentration of less than 400 μmol / l or 4.5 mg / dl, the dose is not changed. In case of severe renal impairment when prescribing the drug, it is necessary to carefully assess the risk-benefit ratio of the proposed therapy.
The dose of Resorba for bone metastases of common malignant tumors and myeloma is prescribed taking into account the initial CC level, which is calculated using the Cockcroft-Gault formula.
Recommended doses of Resorba for patients with mild to moderate renal impairment, taking into account the baseline CC:
- more than 60 ml / min: 4 mg;
- 50-60 ml / min: 3.5 mg;
- 40-49 ml / min: 3.3 mg;
- 30-39 ml / min: 3 mg.
The serum creatinine level should be determined before each administration of zoledronic acid.
The introduction of the next dose of Resorba needs to be postponed if the following renal dysfunction is detected:
- patients with baseline creatinine values less than 1.4 mg / dl: increase in serum creatinine by 0.5 mg / dl;
- Patients with baseline creatinine levels greater than 1.4 mg / dL: Increase in serum creatinine by 1 mg / dL.
The use of Resora at the same dose can be resumed only after the creatinine level exceeds the initial value by no more than 10%.
Side effects
- on the part of the hematopoietic organs: often - anemia; sometimes - leukopenia, thrombocytopenia; rarely - pancytopenia;
- on the part of the cardiovascular system: sometimes - a pronounced decrease or increase in blood pressure (blood pressure); rarely - bradycardia;
- from the gastrointestinal tract: often - nausea, vomiting, anorexia; sometimes - dry mouth, abdominal pain, diarrhea, dyspepsia, constipation, stomatitis;
- from the nervous system: often - headache; sometimes - disturbances in taste, dizziness, hypesthesia, hyperesthesia, paresthesia, sleep disorders, anxiety, tremor, rarely - confusion;
- from the respiratory system: sometimes - cough, shortness of breath;
- from the musculoskeletal system: often - myalgia, bone pain, generalized pain, arthralgia; sometimes - muscle cramps;
- from the urinary system: often - renal dysfunction; sometimes - hematuria, proteinuria, acute renal failure;
- from the immune system: sometimes - hypersensitivity reactions; rarely - angioedema;
- from the side of the organs of vision: often - conjunctivitis; sometimes - "blurring" of visual perception; very rarely - episcleritis, uveitis;
- dermatological reactions: sometimes - increased sweating, skin itching, rash (including erythematous, macular);
- local reactions: irritation, pain, swelling, infiltration at the injection site;
- laboratory parameters: very often - hypophosphatemia; often - hypocalcemia, increased serum urea and creatinine levels; sometimes - hypokalemia, hypomagnesemia; rarely - hypernatremia, hyperkalemia;
- others: often - flu-like syndrome (in the form of general malaise, high body temperature, chills, painful condition), fever; sometimes - peripheral edema, asthenia, chest pain, increased body weight, against the background of dental intervention (including tooth extraction) - the development of osteonecrosis of the jaw; very rarely - a significant decrease in blood pressure, causing fainting, circulatory collapse.
Overdose
Symptoms: impaired renal function, including electrolyte disturbances (including plasma levels of calcium, magnesium, phosphates), renal failure.
Treatment: constant medical supervision, with clinical manifestations of hypocalcemia, drip intravenous administration of calcium gluconate is shown.
special instructions
Resorba should be infused only when the patient is adequately hydrated. If there is a lack of fluid in the body, the introduction of saline is indicated before the infusion, in parallel or after it. At the same time, overhydration of the patient should not be allowed, since this can increase the risk of developing complications from the cardiovascular system.
After the administration of zoledronic acid, it is necessary to regularly monitor the level of concentration in serum of creatinine, calcium, magnesium and phosphorus.
Treatment must be accompanied by careful monitoring of renal function. Risk factors for the development of renal dysfunction are dehydration, the presence of renal failure, a high rate of infusion, repeated administration of zoledronic acid and other bisphosphonates, or the use of nephrotoxic agents. If renal function worsens or renal failure progresses during the first or single administration of Resorba, the need for hemodialysis should be considered.
In patients with bronchial asthma who are sensitive to acetylsalicylic acid, cases of bronchospasm have not been recorded against the background of the use of zoledronic acid. However, since they occur with other bisphosphonates, caution is advised.
Before using bisphosphonates, patients should undergo a dental examination and, if necessary, carry out all therapeutic procedures in the oral cavity. It should be borne in mind that risk factors for the development of osteonecrosis in cancer patients include diseases or poor oral hygiene, infections, anemia, coagulopathy, concomitant chemotherapy or radiation therapy, and the use of corticosteroids. During the treatment period, it is not recommended to carry out dental surgery.
When treating bone metastases with zoledronic acid, the onset of a therapeutic effect should be expected only after 2–3 months of therapy.
Patients with hypocalcemia, hypomagnesemia or hypophosphatemia, if necessary, may be given short-term administration of appropriate drugs.
Influence on the ability to drive vehicles and complex mechanisms
It is necessary to take into account the possibility of developing side effects from the nervous system. In the event of symptoms of malaise, patients need to stop performing work that requires a high reaction rate and increased attention, including driving.
Application during pregnancy and lactation
According to the instructions, Rezorba is contraindicated during the period of gestation and breastfeeding.
Pediatric use
Due to the lack of information on the safety and efficacy of using zoledronic acid in childhood and adolescence, the appointment of the drug in this category of patients is contraindicated.
With impaired renal function
With caution, Rezorba should be prescribed to patients with impaired renal function.
For violations of liver function
It is recommended to prescribe with caution bisphosphonate in severe hepatic insufficiency, since there is no clinical experience with its use.
Drug interactions
When used simultaneously with Resorba:
- antibiotics, other antineoplastic agents, analgesics, diuretics: do not cause clinically significant interactions;
- aminoglycosides: promote an increase in serum calcium concentration and the risk of hypocalcemia, hypomagnesemia;
- drugs with nephrotoxic effects: should be used with caution;
- thalidomide: increases the risk of renal dysfunction in patients with multiple myeloma.
It is forbidden to mix the ready-made solution of lyophilisate with other drugs.
Ringer's solution and other calcium-containing solutions cannot be used as a solvent.
Analogs
The analogues of Rezorba are Zoledronic acid, Veroclast, Aklasta, Blaztera, Zometa, Zolendronic-Rus 4, Zolerix, Zoledronate-Teva, Zoledrex, Rezoklastin FS, Rezoscan.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 25 ° C, protected from moisture and light.
Shelf life: lyophilisate - 3 years, solvent - 5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Rezorba
The few reviews about Rezorbe allow us to imagine the patient's condition after the first infusion. They indicate the development of severe symptoms of a flu-like condition, a significant increase in body temperature. But when repeated infusions are carried out, the development of severe adverse events is not noted. The procedures are much better, conjunctivitis may develop. The effectiveness of Resorba is confirmed by the results of the therapy, in which there is a normalization of the calcium level and a significant reduction in pain.
Price for Rezorba in pharmacies
The price for Rezorba can be: for a package containing 1 bottle of lyophilisate and 1 ampoule of solvent - from 5974 rubles; for a set consisting of 1 bottle of lyophilisate, 1 ampoule of solvent and 100 ml of sodium chloride - from 6142 rubles.
Rezorba: prices in online pharmacies
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Drug name Price Pharmacy |
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Resorba 4 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 4734 Buy |
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Rezorba lyoph. for prig solution for inf. 4mg RUB 5866 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
