Can Zometa (zoledronic acid) be given to a patient with End-Stage Renal Disease (ESRD)?

From the Guidelines

Zometa (zoledronic acid) can be used in patients with end-stage renal disease (ESRD), but dose adjustments are necessary, as recommended by the most recent guidelines 1. For ESRD patients on dialysis, the recommended dose is typically reduced to 3-3.5 mg (rather than the standard 4 mg) with an extended infusion time of at least 30 minutes. Patients with severe renal impairment (creatinine clearance <30 mL/min) generally should not receive Zometa unless the potential benefits outweigh the risks. Close monitoring of renal function before each dose is essential, and treatment should be withheld if renal function deteriorates. Hydration is crucial before administration, though fluid volume should be carefully managed in ESRD patients. The drug works by inhibiting bone resorption, making it useful for treating hypercalcemia of malignancy, bone metastases, and other bone disorders even in ESRD patients. However, these patients are at higher risk for adverse effects including hypocalcemia, so calcium and vitamin D supplementation and regular monitoring of electrolytes are important components of management. Some key considerations for using Zometa in ESRD patients include:

• Monitoring of creatinine clearance to guide dosing 1
• Dose reduction in patients with impaired renal function (estimated creatinine clearance 30–60 mL/min) 1
• Holding Zometa for creatinine clearance <30 mL/min 1
• Risk of severe hypocalcemia and hypophosphatemia, particularly in patients with impaired renal function 1
• Importance of oral hygiene, baseline dental evaluation, and avoidance of invasive dental surgery during therapy to reduce the risk of osteonecrosis of the jaw 1

From the FDA Drug Label

Zoledronic acid injection is excreted intact primarily via the kidney, and the risk of adverse reactions, in particular renal adverse reactions, may be greater in patients with impaired renal function. Safety and pharmacokinetic data are limited in patients with severe renal impairment and the risk of renal deterioration is increased [see Adverse Reactions (6. 1)]. Preexisting renal insufficiency and multiple cycles of zoledronic acid injection and other bisphosphonates are risk factors for subsequent renal deterioration with zoledronic acid injection. Zoledronic acid injection treatment in patients with hypercalcemia of malignancy with severe renal impairment should be considered only after evaluating the risks and benefits of treatment [see Dosage and Administration (2.1)]. Zoledronic acid injection treatment is not recommended in patients with bone metastases with severe renal impairment.

Zometa (zoledronic acid) administration in ESRD patients is not recommended due to the increased risk of renal adverse reactions and limited safety and pharmacokinetic data in patients with severe renal impairment 2, 2, 2.

From the Research

Administration of Zometa in ESRD Patients

• Zometa (zoledronic acid) can be given to patients with end-stage renal disease (ESRD) with certain safety and efficacy measures in place, such as hemodialysis 24 hours after administration and intense monitoring of serum calcium levels 3.
• The use of zoledronic acid in patients with preexisting renal dysfunction may be associated with increased rates of serum creatinine elevations, but it can still be effective in treating hypercalcemia 4.
• There is no significant difference in the incidence of acute kidney injury (AKI) between zoledronic acid and pamidronate in patients with or without baseline renal dysfunction 5.

Safety and Efficacy Considerations

• Zoledronic acid has been shown to be effective in reducing skeletal-related events (SREs) in patients with multiple myeloma or bone metastases secondary to breast cancer, prostate cancer, or other solid tumors 6.
• The drug is generally well-tolerated, with common adverse events including flu-like symptoms, fatigue, gastrointestinal reactions, and anaemia 6.
• Patients with ESRD should be closely monitored for signs of protein-energy wasting and malnutrition, and clinicians should be aware of the many medical complications associated with ESRD 7.

Treatment Guidelines

• Zoledronic acid can be used to treat hypercalcemia of malignancy in patients with and without renal dysfunction, but hydration prior to administration and adherence to the manufacturer's recommended infusion rate are crucial to minimize the risk of AKI 5.
• The decision to initiate dialysis in ESRD patients should be made through shared decision-making, taking into account the patient's overall health and quality of life 7.