Abstract
Background
Analgesic Therapy
Breast cancer and multiple myeloma have been found to be the most responsive tumors to bisphosphonates. Pain relief has been shown to a lesser degree in lung, gastrointestinal, and prostate carcinomas. Standard starting doses include the following: zoledronic acid 4 mg intravenously over 15 minutes and pamidronate 90 mg intravenously administered over 2 hours. Fifty to seventy percent of patients achieve a 30% reduction in pain within a week. The average duration of pain relief is 12 weeks after a single 90-mg infusion of pamidronate. If analgesia is not achieved within a week, the patient can be re-treated. Analgesic effect is related both to the dose per week and the total dose per infusion for pamidronate. Typically patients are treated every 3–4 weeks to achieve maximal effect. If the pain is well controlled, the dosing interval can be extended to a longer period without change in effect.
Prophylaxis
In patients with breast cancer or multiple myeloma, and asymptomatic bone metastases, monthly bisphosphonates decrease skeletal-related events (pathologic fractures, spinal cord compression, surgery to bone, or radiation therapy to bone) by 30%. The dosages of pamidronate and zoledronic acid are the same as used in analgesic therapy. There is no evidence that these medications prevent skeletal-related events in patients without known bone involvement.
Toxicity
Pamidronate and zoledronic acid have the same safety profiles. Both cause an injection site reaction and a flu-like syndrome that responds well to acetaminophen. Less common side effects include hypocalcemia and scleritis. Renal dysfunction is a side effect of long-term, high-dose, or short interval/frequency use of bisphosphonates; this is typically reversible with discontinuation of the drug. Bisphosphonates are contraindicated in renal failure and with patients who experience an increase in creatinine (>0.5 mg/dL over baseline or >1.0 in patients with pre-existing renal insufficiency). In moderate renal dysfunction (creatinine >3.0 mg/dL) the dose of both agents should either be reduced and/or the infusion time increased. Fast Fact #196 discusses bisphosphonate induced osteonecrosis of the jaw.
Cost
The average wholesale price for zoledronic acid 4 mg is $856; the average wholesale price of pamidronate 90 mg is $88. In considering the cost difference between these two drugs it is important to acknowledge the added costs to patients, physicians, and medical facilities for the infusion time of pamidronate (average appointment time 2 hours 52 minutes vs. 1 hour 6 minutes for zoledronic acid).
Footnotes
Version History: This Fast Fact was originally edited by David E Weissman, M.D., and published in January 2005. Current version re-copyedited in April 2009.
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