Can Zometa (zoledronic acid) be given to a 27-year-old male with impaired renal function (creatinine level of 4) and hypercalcemia (calcium level of 17)?

From the Guidelines

Zoledronic acid (Zometa) should not be given to this 27-year-old male with severe renal impairment (creatinine level of 4) and hypercalcemia (calcium level of 17). According to the most recent guidelines, patients with creatinine clearance less than 30 mL/min should not receive zoledronic acid due to the risk of further kidney damage 1. This patient's creatinine level of 4 indicates severe renal dysfunction, making Zometa unsafe. The European Myeloma Network guidelines recommend that pamidronate and zoledronic acid should not be given in patients with CrCl less than 30 mL/min 1. The NCCN Guidelines for MM also recommend denosumab as a preferred option in patients with renal disease 1. Alternative treatments for hypercalcemia should be considered, including aggressive IV fluid hydration with normal saline, loop diuretics after adequate hydration, calcitonin, or dialysis in severe cases. The underlying cause of hypercalcemia should also be investigated and treated.

Some key points to consider in this patient's management include:

• Monitoring renal function closely, as renal deterioration can progress to renal failure and dialysis 1
• Considering alternative treatments for hypercalcemia, such as denosumab, which has been shown to have lower rates of renal toxicity compared to zoledronic acid 1
• Investigating and treating the underlying cause of hypercalcemia
• Providing supportive care to manage symptoms and improve quality of life

It is essential to prioritize the patient's renal function and overall health when making treatment decisions, and to choose alternatives that minimize the risk of further kidney damage. The patient's severe hypercalcemia requires urgent treatment, but safer alternatives must be used given his renal status.

From the FDA Drug Label

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)]. In the clinical studies, patients with serum creatinine greater than 400 μmol/L or greater than 4. 5 mg/dL were excluded.

The patient has a creatinine level of 4, which is close to the excluded range in the clinical studies.

• Renal Impairment: 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.
• Dose Adjustment: The dose of zoledronic acid should be reduced in patients with renal impairment. Given the patient's severe renal impairment and the lack of clear guidance on dose adjustment for a creatinine level of 4, zoledronic acid should be used with caution. The benefits and risks of treatment should be carefully evaluated, and the patient's renal function should be closely monitored. 2 2 2

From the Research

Zometa Administration in Patients with Impaired Renal Function and Hypercalcemia

• The use of Zometa (zoledronic acid) in patients with impaired renal function and hypercalcemia requires careful consideration of the potential risks and benefits.
• According to a study published in 2004 3, zoledronic acid is generally well tolerated, but deterioration of renal function has occasionally been reported in patients receiving the treatment, highlighting the need for monitoring serum creatinine during treatment.
• A 2021 study 4 notes that intravenous zoledronic acid is currently the first-line treatment for hypercalcemia of malignancy, but subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure.
• The safety of zoledronic acid in patients with preexisting kidney impairment is a concern, as reported in a 2024 study 5, which describes cases of acute kidney impairment requiring dialysis after a single administration of intravenous zoledronic acid in patients without a history of cancer.
• A 2003 study 6 reports the first clinical-pathologic study of nephrotoxicity associated with zoledronic acid, which found that all six patients developed renal failure with a rise in serum creatinine after receiving the treatment.
• However, a 2005 study 7 found that zoledronic acid was well tolerated and effective for hypercalcemia of malignancy in Japanese patients, with no serious adverse events associated with renal toxicity reported.

Considerations for Administration in a 27-Year-Old Male with Creatinine of 4 and Calcium Level of 17

• Given the patient's impaired renal function (creatinine level of 4) and hypercalcemia (calcium level of 17), careful consideration of the potential risks and benefits of zoledronic acid treatment is necessary.
• The patient's age and underlying health conditions should also be taken into account when deciding on the appropriate treatment.
• Monitoring of serum creatinine and calcium levels is crucial during treatment with zoledronic acid to minimize the risk of adverse events.
• Alternative treatments, such as subcutaneous denosumab, may be considered in patients with renal failure or bisphosphonate-refractory hypercalcemia 4.