Adverse Effects

Although oral bisphosphonates are generally well tolerated, some patients will experience symptoms of esophagitis. Symptoms often abate with fastidious adherence to recommendations for taking these drugs. If symptoms persist, a proton pump inhibitor at bedtime may be helpful. The oral drugs may be better tolerated when taken once weekly or monthly, with no reduction in efficacy. Patients with active upper GI disease should not be given oral bisphosphonates. Mild fever and aches may accompany the first infusion of pamidronate. These symptoms are short-lived and generally do not recur. Zoledronate has been associated with deterioration of renal function. Thus, zoledronate should be given over at least 15 minutes at a maximum dose of 4 mg. and renal function should be assessed periodically.

Therapeutic Uses hypercalcemia Pamidronate is used parenterally in the management of malignancy-associated hypercalcemia. Zoledronate is also FDA-approved for this indication and appears to be more effective than pamidronate, at least as safe, and can be infused over 15 minutes rather than 4 hours.

postmenopausal osteoporosis The use of bisphosphonates in the prevention and therapy of osteoporosis is described below.

cancer Second- and third-generation bisphosphonates also may act as anticancer drugs by inhibiting the activation of cancer-associated proteins, such as Ras, through suppression of ger-anylgeranylation and farnesylation.

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