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  • Zoledronic Acid Taro 4 mg / 5 ml
    / Taro


    Active Ingredient
    Zoledronic Acid 4 mg / 5 ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    5 ml

    not in the basket chart 11452

    Related information


    Dosage

    The 4 mg/5 mL concentrate should be further diluted with 100 mL 0.9% w/v sodium chloride or 5% w/v glucose solution before infusion. The final solution for infusion should be given as an intravenous infusion of no less than 15 minutes.
    Treatment of hypercalcaemia of malignancy (HCM): Hypercalcaemia of malignancy is defined as albumin corrected serum calcium ≥12 mg/dL [3.0 mmol/L]). In adult and elderly patients the recommended dose is a single 4 mg infusion. Patients must be maintained well hydrated prior to and following administration.
    Multiple myeloma and bone metastases from solid tumors: In adult and elderly patients the recommended dose is a 4 mg infusion given every 3 to 4 weeks. Patients should also be administered an oral calcium supplement of 500 mg and 400 IU vitamin D daily.
    Treatment of patients with renal impairment: Patients with hypercalcaemia of malignancy (HCM): This treatment in adult patients with hypercalcaemia of malignancy (HCM) who also have severe renal impairment should be considered only after evaluating the risks and benefits of treatment. In the clinical studies, patients with serum creatinine >400 micromol/L or >4.5 mg/dL were excluded. No dose adjustment is necessary in HCM patients with serum creatinine <400 micromol/L or <4.5 mg/dL.
    Multiple myeloma and bone metastases of solid tumors: When initiating treatment, serum creatinine levels and creatinine clearance (CLcr) should be determined. CLcr is calculated from serum creatinine levels using the Cockcroft-Gault formula. This product is not recommended for patients presenting with severe renal impairment prior to initiation of therapy, which is defined for this population as CLcr <30 mL/min. In clinical trials with this product, patients with serum creatinine ≥265 micromol/L or ≥3.0 mg/dL were excluded.
    In all patients except patients with HCM presenting with mild to moderate renal impairment prior to initiation of therapy, which is defined for these populations as CLcr 30 to 60 mL/min, the following this dose is recommended.
    Following initiation of therapy, serum creatinine should be measured prior to each dose and treatment should be withheld if renal function has deteriorated. In the clinical trials, renal deterioration was defined as follows:
    For patients with normal baseline serum creatinine (<1.4 mg/dL), an increase of ≥0.5 mg/dL.
    For patients with an abnormal baseline creatinine (>1.4 mg/dL), an increase of ≥1.0 mg/dL.
    In the clinical studies, this treatment was resumed only when the creatinine level returned to within 10% of the baseline value. This product should be resumed at the same dose as that prior to treatment interruption.
    Please refer to the license holder for further details.


    Indications

    Treatment of hypercalcaemia of malignancy. Treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy.


    Contra-Indications

    Hypersensitivity to zoledronic acid or other bisphosphonates or any of the excipients in the formulation of this product. Breast-feeding.


    Special Precautions

    All patients, including patients with mild to moderate renal impairment, must be assessed prior to administration to assure that they are adequately hydrated. Overhydration should be avoided in patients at risk of cardiac failure. Standard hypercalcaemia-related metabolic parameters, such as albumin-corrected serum levels of calcium, phosphate and magnesium as well as serum creatinine should be carefully monitored after initiating therapy. If hypocalcaemia, hypophosphatemia, or hypomagnesaemia occur, short-term supplemental therapy may be necessary. Untreated hypercalcaemia patients generally have some degree of renal function impairment; therefore, careful renal function monitoring should be considered. This product contains the same active ingredient as in Aclasta® (zoledronic acid). Patients being treated with this product should not be treated with Aclasta concomitantly.
    This product should also not be given together with other bisphosphonates since the combined effects of these agents are unknown.
    While not observed in clinical trials with this product, there have been reports of bronchoconstriction in acetylsalicylic acid sensitive asthmatic patients receiving bisphosphonates.
    Renal impairment: Adult patients with HCM and evidence of impairment in renal function should be appropriately evaluated with consideration given as to whether the potential benefit of treatment with this product outweighs the possible risk. The decision to treat patients with bone metastases for the prevention of skeletal related events should consider that the onset of treatment effect is 2 to 3 months. Bisphosphonates have been associated with reports of renal function deterioration. Factors that may increase the potential for deterioration in renal function include dehydration, pre-existing renal impairment, multiple cycles of this product or other bisphosphonates as well as use of nephrotoxic drugs or using a shorter infusion time than currently recommended. While the risk is reduced with a dose of this product 4 mg administered over no less than 15 minutes, deterioration in renal function may still occur. Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose. Increases in serum creatinine also occur in some patients with chronic administration at recommended doses for prevention of skeletal related events, although less frequently. Serum creatinine levels should be measured before each dose. In patients with mild to moderate renal impairment at the initiation of treatment, lower doses are recommended in all adult patients except patients with HCM. In patients who show evidence of renal deterioration during treatment, this product should only be resumed when creatinine level returns to within 10% of baseline value. The use of this product is not recommended in patients with severe renal impairment because there are limited clinical safety and pharmacokinetic data in this population, and there is a risk of renal function deterioration in patients treated with bisphosphonates, including this product. In clinical trials, patients with severe renal impairment were defined as those with baseline serum creatinine ≥400 micromol/L or ≥4.5 mg/dL for patients with HCM and ≥265 micromol/L or ≥3.0 mg/dL for all other patients, respectively. In pharmacokinetic studies, patients with severe renal impairment were defined as those with baseline creatinine clearance <30 mL/min.
    Hepatic impairment: As only limited clinical data are available in patients with severe hepatic impairment, no specific recommendations can be given for this patient population.
    Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ) has been reported predominantly in adult cancer patients treated with bisphosphonates, including this product. Many of these patients were also receiving chemotherapy and corticosteroids. Many had signs of local infection including osteomyelitis. Post-marketing experience and the literature suggest a greater frequency of reports of ONJ based on tumor type (advanced breast cancer, multiple myeloma), and dental status (dental extraction, periodontal disease, local trauma including poorly fitting dentures). Patients should maintain good oral hygiene and should have a dental examination with preventive dentistry prior to treatment with bisphosphonates. While on treatment with bisphosphonates, patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
    Atypical fractures of the femur: Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore, the contralateral femur should be examined in treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of this therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit/risk assessment. Reports of atypical femoral fracture have been received in patients treated with this product; however, causality with this therapy has not been established. During this treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.
    Musculoskeletal pain: In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain have been reported in patients taking bisphosphonates, including this product. The time to onset of symptoms varied from one day to several months after starting treatment. Most patients had relief of symptoms after stopping treatment. A subset had recurrence of symptoms when re-challenged with the same drug or another bisphosphonate.
    Hypocalcaemia: Hypocalcaemia has been reported in patients treated with this product. Cardiac arrhythmias and neurologic adverse events (seizures, tetany, and numbness) have been reported secondary to cases of severe hypocalcaemia. In some instances, the hypocalcaemia may be life-threatening. Caution is advised when this product is administered with other hypocalcaemia causing drugs, as they may have synergistic effect resulting in severe hypocalcaemia. Serum calcium should be measured and hypocalcaemia must be corrected before initiating therapy. Patients should be adequately supplemented with calcium and vitamin D.
    Please refer to the license holder for further details.


    Side Effects

    Bone pain, fever, fatigue, arthralgia, myalgia, rigors and arthritis with subsequent joint swelling.
    Please refer to the license holder for further details.


    Drug interactions

    Caution is advised when bisphosphonates are administered with aminoglycosides, calcitonin or loop diuretics, since these agents may have an additive effect, resulting in a lower serum calcium level for longer periods than required.
    Caution is indicated when zoledronic acid is used with other potentially nephrotoxic medicinal products. Attention should also be paid to the possibility of hypomagnesaemia developing during treatment.
    In multiple myeloma patients, the risk of renal dysfunction may be increased when zoledronic acid is used in combination with thalidomide.
    Caution is advised when zoledronic acid is administered with anti-angiogenic medicinal products, as an increase in the incidence of osteonecrosis of the jaw has been observed in patients treated concomitantly with these medicinal products.
    Please refer to the license holder for further details.


    Pregnancy and Lactation

    Pregnancy: The potential risk in humans is unknown. It should not be used during pregnancy.
    LactationIt is not known whether zoledronic acid is excreted into human milk. This product should not be used by breast-feeding women.
    Please refer to the license holder for further details.


    Overdose

    Clinical experience with acute overdosage of this product is limited. Patients who have received doses higher than those recommended should be carefully monitored, since renal function impairment (including renal failure) and serum electrolyte (including calcium, phosphorus and magnesium) abnormalities have been observed. In the event of hypocalcaemia, calcium gluconate infusions should be administered as clinically indicated.


    Manufacturer
    SUN Pharmaceutical Industries LTD., India
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