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  • Aclasta
    / Novartis


    Active Ingredient
    Zoledronic Acid 5 mg / 100 ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Solution for Infusion

    1 (bottle) x 100 ml

    partial basket chart 71212 1259

    Related information


    Dosage

    Patients must be appropriately hydrated prior to administration of Zoledronic acid. This is especially important for the elderly (≥65 years) and for patients receiving diuretic therapy. Adequate calcium and vitamin D intake are recommended in association with Zoledronic acid administration.
    Osteoporosis: For the treatment of post-menopausal osteoporosis, osteoporosis in men and the treatment and prevention of osteoporosis associated with long-term systemic glucocorticoid therapy, the recommended dose is a single intravenous infusion of 5 mg Zoledronic acid administered once a year. The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of Zoledronic acid on an individual patient basis, particularly after 5 or more years of use. In patients with a recent low-trauma hip fracture, it is recommended to give the Zoledronic acid infusion at least two weeks after hip fracture repair. In patients with a recent low-trauma hip fracture, a loading dose of 50 000 to 125 000 IU of vitamin D given orally or via the intramuscular route is recommended prior to the first Zoledronic acid infusion.
    Prevention of postmenopausal osteoporosis: For the prevention of postmenopausal osteoporosis, the recommended regimen is a single intravenous infusion of 5 mg Zoledronic acid. An annual assessment of the patient’s risk of fracture and clinical response to treatment should guide the decision of when re-treatment should occur.
    Paget’s disease: For the treatment of Paget’s disease, Zoledronic acid should be prescribed only by physicians with experience in the treatment of Paget’s disease of the bone. The recommended dose is a single intravenous infusion of 5 mg Zoledronic acid. In patients with Paget’s disease, it is strongly advised that adequate supplemental calcium corresponding to at least 500 mg elemental calcium twice daily is ensured for at least 10 days following Zoledronic acid administration. Re-treatment of Paget’s disease: After initial treatment with Zoledronic acid in Paget’s disease, an extended remission period is observed in responding patients. Re-treatment consists of an additional intravenous infusion of 5 mg Zoledronic acid after an interval of one year or longer from initial treatment in patients who have relapsed. Limited data on re-treatment of Paget’s disease are available.
    Special populations
    Patients with renal impairment: Aclasta is contraindicated in patients with creatinine clearance < 35 ml/min. No dose adjustment is necessary in patients with creatinine clearance ≥ 35 mL/min.
    Patients with hepatic impairment: No dose adjustment is required.
    Elderly (≥ 65 years): No dose adjustment is necessary since bioavailability, distribution and elimination were similar in elderly patients and younger subjects.
    Paediatric population: The safety and efficacy of Zoledronic acid in children and adolescents below 18 years of age have not been established. No data are available.
    Method of administration: Intravenous use. Zoledronic acid is administered via a vented infusion line and given slowly at a constant infusion rate. The infusion time must not be less than 15 minutes.


    recommended drugs

    Indications

    Treatment of Paget’s disease of the bone. Treatment of osteoporosis:  in post-menopausal women and in men at increased risk of fracture including those with a recent low-trauma hip fracture. Treatment and prevention of glucocorticoid-induced osteoporosis. Prevention of postmenopausal osteoporosis in women for whom bisphosphonate therapy is indicated.


    Contra-Indications

    HypocalcaemiaSevere renal impairment with creatinine clearance <35 mL/min; Pregnancy and breast-feeding women; Hypersensitivity to the active substance or to any of the excipients or to any bisphosphonates.


    Special Precautions

    Renal function: The use of Zoledronic acid in patients with severe renal impairment (creatinine clearance <35 mL/min) is contraindicated due to an increased risk of renal failure in this population. Renal impairment has been observed following the administration of Zoledronic acid, especially in patients with pre-existing renal dysfunction or other risk factors including advanced age, concomitant nephrotoxic medicinal products, concomitant diuretic therapy, or dehydration occurring after Zoledronic acid administration. Renal impairment has been observed in patients after a single administration. Renal failure requiring dialysis or with a fatal outcome has rarely occurred in patients with underlying renal impairment or with any of the risk factors described above.
    The following precautions should be taken into account to minimise the risk of renal adverse reactions: Creatinine clearance should be calculated based on actual body weight using the Cockcroft-Gault formula before each Zoledronic acid dose. Transient increase in serum creatinine may be greater in patients with underlying impaired renal function. Monitoring of serum creatinine should be considered in at-risk patients. Zoledronic acid should be used with caution when concomitantly used with other medicinal products that could impact renal function. Patients, especially elderly patients and those receiving diuretic therapy, should be appropriately hydrated prior to administration of Zoledronic acid. A single dose of Zoledronic acid should not exceed 5 mg and the duration of infusion should be at least than 15 minutes.
    Hypocalcaemia: Pre-existing hypocalcaemia must be treated by adequate intake of calcium and vitamin D before initiating therapy with Zoledronic acid.  Other disturbances of mineral metabolism must also be effectively treated (e.g. diminished parathyroid reserve, intestinal calcium malabsorption). Physicians should consider clinical monitoring for these patients. Elevated bone turnover is a characteristic of Paget’s disease of the bone. Due to the rapid onset of effect of zoledronic acid on bone turnover, transient hypocalcaemia, sometimes symptomatic, may develop and is usually maximal within the first 10 days after infusion of Zoledronic acid. Adequate vitamin D intake is recommended in association with Zoledronic acid administration. In addition, in patients with Paget’s disease, it is strongly advised that adequate supplemental calcium corresponding to at least 500 mg elemental calcium twice daily is ensured for at least 10 days following Zoledronic acid administration. Patients should be informed about symptoms of hypocalcaemia and receive adequate clinical monitoring during the period of risk. Measurement of serum calcium before infusion of Zoledronic acid is recommended for patients with Paget´s disease. Severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including zoledronic acid.
    Osteonecrosis of the Jaw (ONJ): ONJ has been reported in the post-marketing setting in patients receiving zoledronic acid for osteoporosis. The start of treatment or of a new course of treatment should be delayed in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment with Zoledronic acid in patients with concomitant risk factors. The following should be considered when evaluating a patient’s risk of developing ONJ:
    – Potency of the medicinal product that inhibits bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration) and cumulative dose of bone resorption therapy.
    – Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking.
    – Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck.
    – Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures, e.g. tooth extractions.
    All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, non-healing of sores or discharge during treatment with zoledronic acid. While on treatment, invasive dental procedures should be performed with caution and avoided in close proximity to zoledronic acid treatment. The management plan for patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary interruption of zoledronic acid treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible.
    Osteonecrosis of other bones: Cases of osteonecrosis of other bones (including femur, hip, knee and humerus) have also been reported; however, causality has not been determined in the population treated with Zoledronic acid.
    Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.
    Atypical fractures of the femur: Atypical subtrochanteric and diaphyseal femoral fractures have been reported with 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 bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate 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. During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for possible femur fracture.
    General: The incidence of post-dose symptoms occurring within the first three days after administration of Zoledronic acid can be reduced with the administration of paracetamol or ibuprofen shortly following Zoledronic acid a administration. Other products containing zoledronic acid as an active substance are available for oncology indications. Patients being treated with Zoledronic acid  should not be treated with such products or any other bisphosphonate concomitantly, since the combined effects of these agents are unknown. This medicinal product contains less than 1 mmol sodium (23 mg) per 100 ml vial of Zoledronic acid, i.e. essentially “sodium free”.
    See prescribing information for full details.


    Side Effects

    Very common: Pyrexia, Pain, chills, Myalgia.
    Common:
    Hypocalcemia, Headache, dizziness, Ocular hyperaemia, Atrial fibrillation, Nausea, vomiting, diarrhoea, Myalgia, arthralgia, bone pain, back pain, pain in extremity. Influenza-like illness, chills, fatigue, asthenia, pain, malaise, infusion site reaction. C-reactive protein increased. Decreased appetite, Tremor, lethargy. Conjunctivitis, eye pain, iritis, Abdominal pain, abdominal pain upper, constipation, Night sweats, Musculoskeletal pain, muscle spasms, musculoskeletal chest pain, pain in jaw, neck pain, Oedema peripheral, non cardiac chest pain.
    See prescribing information for full details.


    Drug interactions

    No interaction studies with other medicinal products have been performed. Zoledronic acid is not systemically metabolised and does not affect human cytochrome P450 enzymes in vitro. Zoledronic acid is not highly bound to plasma proteins (approximately 43-55% bound) and interactions resulting from displacement of highly protein-bound medicinal products are therefore unlikely.
    Zoledronic acid is eliminated by renal excretion. Caution is indicated when zoledronic acid is administered in conjunction with medicinal products that can significantly impact renal function (e.g. aminoglycosides or diuretics that may cause dehydration).
    In patients with renal impairment, the systemic exposure to concomitant medicinal products that are primarily excreted via the kidney may increase.


    Pregnancy and Lactation

    Pregnancy: This product is contraindicated during pregnancy. There are no data on the use of zoledronic acid in pregnant women. The potential risk in humans is unknown.
    Lactation: This product is contraindicated in breast-feeding women.
    See prescribing information for full details.


    Overdose

    Clinical experience with acute overdosage is limited. Patients who have received doses higher than those recommended should be carefully monitored. In the event of overdose leading to clinically significant hypocalcaemia, reversal may be achieved with supplemental oral calcium and/or an infusion of calcium gluconate.


    Important notes

    Incompatibilities: This medicinal product must not be allowed to come into contact with any calcium-containing solutions. Aclasta must not be mixed or given intravenously with any other medicinal products.
    Shelf-life: After opening, the solution is chemically and physically stable for at least 24 hours at 2 to 8°C.
    Storage: The unopened bottle should be stored below 30⁰C.
    See prescribing information for full details.


    Manufacturer
    Fresenius Kabi
    Licence holder
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