7 DRUG INTERACTIONS
In vitro studies indicate that the plasma protein binding of zoledronic acid is low, with the unbound fraction ranging from 60% to 77%. In vitro studies also indicate that zoledronic acid does not inhibit microsomal CYP450 enzymes. In vivo studies showed that zoledronic acid is not metabolized, and is excreted into the urine as the intact drug.
7.1 Aminoglycosides and Calcitonin
Caution is advised when bisphosphonates are administered with aminoglycosides or calcitonin, since these agents may have an additive effect to lower serum calcium level for prolonged periods. This effect has not been reported in zoledronic acid clinical trials.
7.2 Loop Diuretics
Caution should also be exercised when zoledronic acid is used in combination with loop diuretics due to an increased risk of hypocalcemia.
7.3 Nephrotoxic Drugs
Caution is indicated when zoledronic acid is used with other potentially nephrotoxic drugs.
No dose adjustment for zoledronic acid 4 mg is needed when coadministered with thalidomide. In a pharmacokinetic study of 24 patients with multiple myeloma, zoledronic acid 4 mg given as a 15-minute infusion was administered either alone or with thalidomide (100 mg once daily on days 1–14 and 200 mg once daily on days 15–28). Coadministration of thalidomide with zoledronic acid did not significantly change the pharmacokinetics of zoledronic acid or creatinine clearance.