There is a well-known risk of deterioration in renal function with intravenous bisphosphonates administered at a rapid infusion rate.
ADRAC ( Adverse Drug Reactions Advisory Committee ) has received few reports of renal impairment or failure with Pamidronate ( Aredia ) and the oral bisphosphonates Risedronate ( Actonel ) and Alendronate ( Fosamax ), but there is a significant number with Zoledronic acid ( 31 from a total of 268 reports for this drug ). While the deterioration in renal function with Zoledronic acid ( Zometa ) was usually acute, in many cases it did not appear to be related to a rapid infusion rate.

The 31 reports in association with Zoledronic acid describe either renal failure ( 16 ) or renal impairment ( 15 ). It was the only suspected drug in 20 of the 31 reports. Interstitial nephritis was described in 3 of the reports. Ages ranged from 44 to 88 years ( median 63 years ). Time to onset in about two thirds of the reports was between 1 and 3 months after starting zoledronic acid. Recovery was mostly unknown or unspecified.

Zoledronic acid was being used for a variety of indications with multiple myeloma ( 13 cases ) the most common but also breast cancer ( 5 ), prostate cancer ( 4 ), plasmacytoma, malignant melanoma, osteoporosis, bone metastases and osteomyelitis ( 1 case each ). Only 4 reports did not specify the reason for use.

The Zometa product information, under Precautions, includes comprehensive information on the need to monitor renal function and use in patients with pre-existing renal impairment. It also provides detailed information on risk factors for renal adverse events which include dehydration, pre-existing renal impairment, multiple cycles of bisphosphonates, as well as the use of other nephrotoxic drugs, or using an infusion time shorter than 15 minutes. Renal impairment and renal failure are both mentioned under Adverse Reactions as common ( 1-10% ) and uncommon ( 0.1-1% ), respectively.

Reports to ADRAC suggest renal impairment and renal failure may occur more commonly with Zoledronic acid than with other bisphosphonates.

In several cases, the delayed onset of renal toxicity suggests the impairment was unrelated to the infusion rate; although the conditions in which Zoledronic acid is used may predispose patients to renal impairment. Many of the reports described patients with pre-existing renal impairment, and the use of Zoledronic acid in multiple myeloma is also a confounding factor.

Source: Australian Adverse Drug Reactions Bulletin, 2007

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