Tuesday, September 25, 2012

Hypercalcemia: Pamidronate vs Zoledronic acid


We use IV bisphosphonates in acute hypercalcemia with theunderstanding that they’ll help achieve a normal calcium level in about 72hours.  Aside from the importantcomponents of this treatment that will have more of an immediate effect (fluid,diuretics, steroids, calcitonin); which bisphosphonate is best?

Since oral bisphosphonates have extremely low bioavailablity(1-2%), IV agents like pamidronate and zoledronic acid become the two leadingcandidates.

Even though these drugs do reach their peak effect for days,we do want to administer them as soon as possible (often in the ED).  Zoledronic acid can be given over 15minutes; faster than pamidronate, which must be infused over 2 - 4 hours. 

There is only one study comparing the two agents head tohead (pamidronate 90mg, zoledronic acid 4mg, and zoledronic 8mg).  The study showed that zoledronic acid issuperior compared to pamidronate at achieving a “complete response” which wasdefined as a corrected serum calcium level less than 10.8 mg/dL by day 10 (88.4%vs 69.7%, respectively).  Although thisdifference reached statistical significance, its clinical significance as wellas the clinical significance of the mean nadir corrected calcium concentrations(zoledronic acid 9.8mg/dL; pamidronate 10.5mg/dL) is disputed. [Major P, et al. J Clin Oncol 19:558-567]

Regarding safety, both agents have similar incidences ofnephrotoxicity, flu-like symptoms after infusion (often, acetaminophen beforeinfusion can prevent this). Zoledronic does require dose adjustment for renalimpairment, and both should generally be avoided if GFR is less than 30 mL/min.

Cost… Zoledronic acid 4mg - $1100 per dose. Pamidronate90mg - $100 per dose.  I don’t usuallyget hung up on cost differences between drugs, but in this case with this evidence, andsafety profile, it’s hard to justify utilizing a drug that is 10x moreexpensive than it’s alternative. 

My recommendation (after adequate fluid, calciuresis,calcitonin, steroids):

First line:
Pamidronate 90mg IV in 1000mL NS, infuse over 4 hours

Second line:
Zoledronic acid 4mg IV in 100mL NS, infuse over 15 min
GFR 50-59 mL/min: 3.5 mg
GFR 40-49 mL/min: 3.3 mg
GFR 30-39 mL/min: 3.0 mg