Veroclast, 4 mg/5 ml, concentrate for solution for infusion, 1 pc.
Before infusing zoledronic acid, ensure that the patient is adequately hydrated. If necessary, administration of 0.9% sodium chloride solution is recommended before, during or after the infusion of zoledronic acid. Overhydration of the patient should be avoided due to the risk of cardiovascular complications.
After administration of zoledronic acid, 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 additional administration of the corresponding substances may be necessary. Patients with untreated hypercalcemia usually have impaired renal function, so careful monitoring of renal function in this category of patients is necessary.
When deciding whether to treat patients with bone metastases with zoledronic acid, it should be taken into account that the therapeutic effect occurs 2-3 months after the start of treatment with zoledronic acid.
There are isolated reports of renal dysfunction associated with the use of bisphosphonates. Risk factors for 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. Although the risk of the above-described complications is reduced when zoledronic acid is administered at a dose of 4 mg over at least 15 minutes, the possibility of renal dysfunction remains. There have been cases of deterioration in renal function, progression of renal failure and the need for hemodialysis with the first or single use of zoledronic acid.
Increases in serum creatinine concentrations have also been observed in some patients with long-term use of zoledronic acid at recommended doses, although less frequently.
Since there are limited clinical data on the use of the drug in patients with severe liver failure, it is not possible to make specific recommendations for this category of patients.
When deciding on the use of zoledronic acid in patients with hypercalcemia caused by 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 administering the drug outweighs the possible risk.
Serum creatinine concentrations should be determined before each administration of zoledronic acid. At the beginning of treatment with the drug in patients with bone metastases and with mild to moderate renal dysfunction, it is recommended to use zoledronic acid in reduced doses. In patients who develop renal impairment during therapy with zoledronic acid, therapy with the drug can be continued only after the serum creatinine concentration returns to values that are within 10% of the initial value.
Cases of osteonecrosis of the jaw in cancer patients during treatment with bisphosphonates, including zoledronic acid, have been described. Many patients had signs of a local infectious and inflammatory process, including osteomyelitis.
In clinical practice, the development of osteonecrosis of the jaw was most often observed in patients with advanced breast cancer and multiple myeloma, as well as in the presence of dental diseases (after tooth extraction, periodontal diseases, unsatisfactory fixation of dentures). Known risk factors for the development of osteonecrosis of the jaw are cancer, concomitant treatment (chemotherapy, radiation therapy, treatment with glucocorticosteroids), concomitant diseases (anemia, coagulopathy, infection, previous oral disease).
Before prescribing bisphosphonates, patients should undergo a dental examination and necessary preventive procedures, and should be advised to maintain strict oral hygiene. Dental surgery should be avoided if possible during treatment of these patients. There is no evidence that interrupting bisphosphonate treatment before dental procedures reduces the risk of developing 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, rare cases 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. Symptoms resolved in most patients after treatment was stopped. In several patients, symptoms recurred when therapy was restarted or another bisphosphonate was prescribed.
The effectiveness and safety of zoledronic acid in pediatric practice have not yet been established.
Impact on the ability to drive vehicles and other mechanisms
There is no information on the effect of zoledronic acid on the ability to drive vehicles and other mechanisms.
Release form and composition
Veroclast is available in the following forms:
- concentrate for preparing a solution for infusion (5 ml in plastic bottles, 1 bottle in a cardboard box or in cardboard boxes of 50 or 80 bottles);
- lyophilisate for preparing a solution for infusion (4 mg in dark glass bottles, 1 bottle in a cardboard box).
1 bottle of concentrate for the preparation of solution for infusion contains 4 mg of zoledronic acid.
1 bottle of lyophilisate for preparing a solution for infusion contains 4 mg of zoledronic acid.
Drug interactions
Veroclast is used with caution simultaneously with aminoglycosides and drugs that can potentially cause nephrotoxicity.
In patients with multiple myeloma, simultaneous intravenous administration of bisphosphonates and thalidomide may increase the likelihood of renal dysfunction.
Zoledronic acid solution should not be mixed with solutions or preparations containing calcium or any other divalent cations. To administer the drug, you must use a separate infusion system.
Contraindications
Absolute:
- severe renal dysfunction (creatinine clearance less than 30 ml/min);
- children and adolescents under 18 years of age (since the effectiveness and safety of the drug have not been studied);
- period of pregnancy and lactation;
- hypersensitivity to the drug and other bisphosphonates.
Relative (Veroclast is used with caution):
- mild to moderate renal dysfunction;
- bronchial asthma in patients sensitive to acetylsalicylic acid.
Directions for use and dosage
Veroclast is administered intravenously by drip for at least 15 minutes.
For hypercalcemia induced by malignant neoplasms (serum calcium concentration more than 3 mmol/l or 12 mg/dl), the maximum recommended dose of the drug is 4 mg.
Before administering Veroclast, it is necessary to check the serum creatinine concentration. For mild or moderate renal failure, no dosage adjustment is required. The infusion is carried out provided that the patient is adequately hydrated. To do this, a 0.9% sodium chloride solution is administered before, simultaneously with, or after the infusion. Repeated administration of Veroclast at a dose of 4 mg is indicated if the condition worsens after the therapeutic effect has been achieved or in case of resistance to the first administration. There should be an interval of at least one week between the first and repeated infusions to adequately assess the effect. The serum creatinine concentration must be determined before each administration of the drug.
For multiple myeloma and bone metastases, the recommended dose for normal renal function is 4 mg every 3–4 weeks. For mild or moderate renal impairment, the dose of Veroclast is reduced depending on creatinine clearance. Before each dose, the serum creatinine concentration is determined. If renal dysfunction is detected, the next dose of the drug should be postponed. To determine renal dysfunction, the following parameters are used:
- patients with normal baseline creatinine levels – increase in serum creatinine concentration by 0.5 mg/dl;
- patients with deviations in baseline creatinine levels - an increase in serum creatinine concentration by 1 mg/dl.
Treatment is resumed only after reaching a creatinine concentration level within 10% of the initial value.
In addition to Veroclast therapy, oral calcium (500 mg per day) and oral vitamin D (400 IU per day) are prescribed.
Before administering the drug, it is necessary to prepare a solution for infusion. The contents of one bottle of concentrate are diluted in 100 ml of solution for infusion. A 5% dextrose solution or a 0.9% sodium chloride solution can be used as a solvent. It is advisable to use the finished solution immediately after dilution. The prepared infusion solution can be stored at a temperature of +2… +8 °C, but not more than 24 hours. Before administration, it should be brought to room temperature by keeping it indoors for some time.
special instructions
After administration of Veroclast, it is necessary to constantly monitor the concentrations of creatinine, phosphorus, calcium and magnesium in the serum. In patients with untreated hypercalcemia, renal function should be monitored particularly carefully.
Before prescribing bisphosphonates, a complete dental examination and preventative procedures should be performed. Strict oral hygiene is also recommended. During the treatment period, it is advisable to avoid dental operations.
There is no information on the effect of Veroclast on the patient’s ability to drive a car, other vehicles and potentially dangerous machinery.
Side effects
- digestive system: often – anorexia, vomiting and nausea; uncommon – dyspeptic disorders, dry mouth, abdominal pain, stomatitis, diarrhea or constipation;
- cardiovascular system: infrequently - a pronounced increase in blood pressure; rarely – bradycardia;
- respiratory system: infrequently – cough, shortness of breath;
- hematopoietic system: often – anemia; uncommon – leukopenia, thrombocytopenia; rarely - pancytopenia;
- nervous system: often – headaches; uncommon – disturbance of taste, anxiety, paresthesia, hyperesthesia, hypoesthesia, sleep disorders, dizziness, tremor; rarely – confusion;
- sense organs: often – conjunctivitis; infrequently – blurred visual perception; very rarely – episcleritis, uveitis;
- musculoskeletal system: often - muscle and joint pain, generalized pain, bone pain; infrequently – convulsions;
- urinary system: often - renal dysfunction; uncommon – hematuria, acute renal failure, proteinuria;
- skin and skin appendages: uncommon – increased sweating, itching, rash;
- laboratory indicators: very often – decrease in the level of phosphates in the blood; often - decreased calcium levels in the blood, increased concentrations of urea and creatinine in the serum; uncommon – decreased levels of potassium and magnesium in the blood; rarely - increased levels of sodium and potassium in the blood;
- immune system: uncommon – hypersensitivity reactions; rarely - Quincke's edema;
- other reactions: often – flu-like syndrome, fever; uncommon – peripheral edema, weight gain, asthenia, chest pain;
- local reactions: swelling, irritation, formation of infiltrate and pain at the injection site.
Bisphosphonates, including zoledronic acid, can cause osteonecrosis of the jaw (a few such cases have been reported, usually occurring after tooth extraction or other dental surgery).
Very rarely, the following reactions have been observed with the use of zoledronic acid: a marked decrease in blood pressure, which led to circulatory collapse or fainting (more often in patients with risk factors), atrial fibrillation, bronchoconstriction and drowsiness.
