Drug Interactions between pamidronate and tobramycin

MONITOR: Coadministration of bisphosphonates and aminoglycosides may potentiate the risks of hypocalcemia and nephrotoxicity, particularly when the bisphosphonate is administered intravenously. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium, while aminoglycosides can induce renal tubular damage resulting in renal loss of calcium and magnesium. Hypomagnesemia, in turn, may also lead to peripheral parathyroid hormone resistance and impaired parathyroid hormone secretion, thus compromising the normal homeostatic response to hypocalcemia. The interaction has been reported in a 62-year-old patient with multiple myeloma who developed persistent, severe hypocalcemia and hypomagnesemia after treatment with oral clodronate and netilmicin. The electrolyte abnormalities were accompanied by increased serum creatinine concentration and grand mal seizures. Administration of bisphosphonates, especially by rapid IV injection, has also been associated with nephrotoxicity manifested as deterioration of renal function and renal failure.

MANAGEMENT: Caution is advised if bisphosphonates are used in patients who have recently received or are receiving treatment with aminoglycosides. Renal function as well as serum calcium and magnesium levels should be monitored during and after treatment, since renal loss of calcium and magnesium can continue for many weeks after cessation of aminoglycosides, as can the effect of bisphosphonates. Patients and clinicians should be alert to signs and symptoms of clinical hypocalcemia such as muscle spasms, carpopedal spasm, laryngeal spasm, tetany, convulsions, mental changes (irritability, depression, psychosis), increased intracranial pressure, papilledema, QT interval prolongation, and cardiac arrhythmias. For IV bisphosphonates, product labelings for pamidronate and zoledronic acid recommend that single doses not exceed 90 mg and 4 mg, respectively, and duration of infusion not less than 2 hours and 15 minutes, respectively.