Zoledronic acid has several advantages over other bisphosphonates. In addition to having broader clinical utility, zoledronic acid can safely be infused over 15 minutes rather than the 2 hours recommended for pamidronate. The infusion protocol for zoledronic acid is briefly outlined in Table 1 . [20] The maximum recommended zoledronic acid dose for the treatment of bone metastases is 4 mg by IV infusion, infused over no less than 15 minutes. Preinfusion examinations include a physical examination, vital signs, and blood samples for laboratory testing to assess hydration status and renal function.
The step-by-step infusion protocol and preformatted infusion logs are also accessible online (https://www.us.zometa.com/hcp/productinfo/infusioninstructions.jsp). Zoledronic acid is prepared by diluting the 5-mL solution in no less than 100 mL of infusate. [20] If necessary, the diluted infusion solution can be stored in the refrigerator for up to 24 hours, and then allowed to warm to room temperature before use. A peripheral IV line should be initiated, and the 100-mL zoledronic acid solution infused over no less than 15 minutes. This corresponds to a drip rate of 133 drops/minute or 33 drops/15 seconds, based on a tubing drip factor of 20 drops/mL.
The patient's vital signs should be monitored before and after the infusion, and the IV insertion site inspected for redness, tenderness, swelling, leakage, or temperature elevations periodically during the infusion and after the needle has been removed. These changes may indicate a transient infusion site reaction or the development of an allergic response to the medication. In clinical trials of bisphosphonates, infusion-site reactions were occasionally reported and were never severe, and allergic responses were rare. [13,19,21] However, an allergic response is possible during the infusion of any medication. If an allergic reaction is suspected, the infusion should be stopped immediately and the patient closely monitored until the reaction stabilizes. Antihistamines or steroidal medications may be needed to resolve symptoms. [22]
Following every bisphosphonate infusion, patients should be reminded to take their daily vitamin and mineral supplements and counseled about the possibility of adverse reactions. An appointment for their next serum creatinine assessment should be scheduled.
The brief infusion of zoledronic acid represents a significant time savings compared with the 2-hour infusion recommended for 90 mg pamidronate, particularly for patients who receive chemotherapy on the day of their bisphosphonate therapy. Consequently, many patients prefer the shorter, more convenient infusion. [23] Additionally, the shorter infusion requires less nurse monitoring time and increases infusion chair availability in busy infusion centers. [24] A microcosting analysis of patients receiving bisphosphonate therapy determined that the average visit time required to receive zoledronic acid was 1 hour and 6 minutes, compared with 2 hours and 52 minutes for patients receiving pamidronate. [25] Furthermore, the shorter infusion of zoledronic acid made an additional 1.8 infusion chairs per day available in a typical oncology practice. Therefore, in addition to the potential quality-of-life benefits to the patient, these analyses suggest that the shorter infusion time for zoledronic acid compared with that for pamidronate may reduce the burden on healthcare resources in busy infusion centers and hospitals.