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Drug Products with Same Active Ingredient: Patients being treated with zoledronic acid injection should not be treated with other drugs containing zoledronic acid or other bisphosphonates concomitantly.
Hypocalcemia and Mineral Metabolism: Pre-existing hypocalcemia and disturbances of mineral metabolism (e.g., hypoparathyroidism, thyroid surgery, parathyroid surgery; malabsorption syndromes, excision of small intestine) must be effectively treated before initiating therapy with Zoledronic acid. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended for these patients.
Hypocalcemia following Zoruxa administration is a significant risk in Paget's disease. All patients should be instructed about the symptoms of hypocalcemia and the importance of calcium and vitamin D supplementation in maintaining serum calcium levels.
All osteoporosis patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels.
Renal Impairment: A single dose of Zoledronic acid should not exceed 5 mg and the duration of infusion should be no less than 15 minutes.
Zoledronic acid is contraindicated in patients with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment. If history or physical signs suggest dehydration, Zoledronic acid therapy should be withheld until normovolemic status has been achieved.
Zoledronic acid should be used with caution in patients with chronic renal impairment. Acute renal impairment, including renal failure, has been observed following the administration of zoledronic acid, especially in patients with pre-existing renal compromise, advanced age, concomitant nephrotoxic medications, concomitant diuretic therapy, or severe dehydration occurring before or after Zoledronic acid administration. Acute renal failure (ARF) has been observed in patients after a single administration. Rare reports of hospitalization and/or dialysis or fatal outcome occurred in patients with underlying moderate to severe renal impairment or with any of the risk factors described in this section. Renal impairment may lead to increased exposure of concomitant medications and/or their metabolites that are primarily renally excreted.
Creatinine clearance should be calculated based on actual body weight using Cockcroft-Gault formula before each Zoledronic acid dose. Transient increase in serum creatinine may be greater in patients with impaired renal function; interim monitoring of creatinine clearance should be performed in at risk patients. Elderly patients and those receiving diuretic therapy are at increased risk of acute renal failure. These patients should have their fluid status assessed and be appropriately hydrated prior to administration of Zoledronic acid. Zoledronic acid should be used with caution with other nephrotoxic drugs. Consider monitoring creatinine clearance in patients at-risk for ARF who are taking concomitant medications that are primarily excreted by the kidney.
Osteonecrosis of the Jaw: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates, including Zoledronic acid. Most cases have been in cancer patients treated with intravenous bisphosphonates undergoing dental procedures. Some cases have occurred in patients with postmenopausal osteoporosis treated with either oral or intravenous bisphosphonates. A routine oral examination should be performed by the prescriber prior to initiation of bisphosphonate treatment. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with a history of concomitant risk factors (e.g., cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene, pre-existing dental disease or infection, anemia, coagulopathy).
While on treatment, patients with concomitant risk factors should avoid invasive dental procedures if possible. For patients who develop ONJ 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 ONJ. The clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short obliquein orientation without evidence of commination. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates.
Atypical femur fractures most commonly occur with minimal or no trauma to the affected area.They maybe bilateral and many patients report prodromal pain in the affected area, usually presenting as dun, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g., prednisone) at the time of fracture.
Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Musculoskeletal Pain: In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including zoledronic acid. The time to onset of symptoms varied from one day to several months after starting the drug. Consider withholding future zoledronic acid treatment if severe symptoms develop. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.
Respiratory effects: While not observed in clinical trials with zoledronic acid, there have been reports of bronchoconstrictionin aspirin-sensitive patients receiving bisphosphonates. Use zoledronic acid with caution in aspirin-sensitive patients.
Important Limitations of Use: The safety and effectiveness of Zolendronic acid for the treatment of osteoporosis is based on clinical data of three years duration. The optimal duration of use has not been determined. All patients on biphosphonates therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3-5 years of use. Patients who discontinue should have their risk for fracture re-evaluated periodically.
Renal Impairment: Zoledronic acid is contraindicated in patients with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment. There is no safety or efficacy data to support the adjustment of the Zoledronic acid dose based on baseline renal function. Therefore, no dosage adjustment is required in patients with a creatinine clearance of ≥35 mL/min. Risk of acute renal failure may increase with underlying renal disease and dehydration secondary to fever, sepsis, gastrointestinal losses, diuretic therapy, advanced age, etc.
Effects on Ability to Drive and Operate Machines: Adverse reactions, such as dizziness, may affect the ability to drive or use machines, though no studies on this effect with Zoledronic acid have been performed.
Use in Pregnancy: IT SHOULD NOT BE USED DURING PREGNANCY. Zoledronic acid may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while on Zoruxa therapy (see Use in Pregnancy & Lactation).
Use in Elderly: Because of decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.
