Article date: April 2010
Zoledronic acid 5 mg for infusion (Aclasta▼) is used for the once-yearly treatment of osteoporosis in patients at increased risk of fracture, and as a single dose for the treatment of Paget’s disease of the bone.
Zoledronic acid 4 mg for infusion (Zometa) is given every 3–4 weeks for the reduction of bone damage in advanced malignancies involving bone, and as a single dose for tumour-induced hypercalcaemia.
Zoledronic acid is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction or other risk factors. The product information for Zometa already contains strong warnings and precautions regarding renal impairment and renal failure.
Warnings in the product information for Aclasta▼ are being strengthened following reports of renal failure or renal impairment with its use. There have been 139 worldwide suspected reports (14 fatal) of renal impairment or renal failure up to 14 August 2009, and six UK suspected reports (one fatal) of renal impairment or renal failure up to 5 March 2010, following the administration of Aclasta▼. The majority of cases were associated with the first dose, and generally occurred in patients with pre-existing renal dysfunction or other risk factors, including: advanced age; use of concomitant nephrotoxic drugs or diuretic therapy; or dehydration. Renal failure requiring dialysis or resulting in death has occurred in some at-risk patients.
A letter was sent to healthcare professionals in March 2010, regarding the updated product information for Aclasta▼.
Advice for healthcare professionals
The following precautions should be taken into account to minimise the risk of renal adverse reactions with zoledronic acid:
for all patients receiving zoledronic acid:
- renal function should be measured before each infusion of zoledronic acid
- patients, especially elderly patients and those receiving diuretic therapy, should be appropriately hydrated before administration of zoledronic acid
- the duration of infusion of zoledronic acid should be at least 15 minutes
- monitoring of renal function after zoledronic acid infusion should be considered, particularly in at-risk patients such as: those with pre-existing renal dysfunction; those of advanced age; those using concomitant nephrotoxic drugs or diuretic therapy; or those who are dehydrated
- zoledronic acid should be used with caution when used concomitantly with medicines that could affect renal function
for patients receiving AclastaAclasta▼:
- A single dose of Aclasta▼ for the treatment of osteoporosis and Paget’s disease of the bone should not exceed 5 mg
- Aclasta▼ should not be used in patients with creatinine clearance <35 mL/min
for patients receiving ZometaZometa
- The recommended dose for Zometa in patients with normal renal function is 4 mg, which should be reduced in patients with mild-to-moderate renal impairment
- Zometa for cancer treatment is not recommended for use in patients with creatinine clearance <30 mL/min, and should only be considered for the treatment of hypercalcaemia in cancer patients with severe renal impairment after evaluating the risk and benefits of treatment
- In patients who show evidence of renal deterioration during the treatment period, Zometa should be with-held and only resumed when serum creatinine returns to within 10% of baseline
Article citation: Drug Safety Update April 2010, vol 3 issue 9: 6.