Abstract
A randomized, double-blind, placebo-controlled study assessed the efficacy of acetaminophen or fluvastatin in preventing post-dose symptoms (increases in body temperature or use of rescue medication) following a single infusion of the intravenous (IV) bisphosphonate zoledronic acid (ZOL). Acetaminophen, but not fluvastatin, significantly reduced the incidence and severity of post-dose symptoms. INTRODUCTION: Transient symptoms including myalgia and pyrexia have been reported post-infusion of IV bisphosphonates, typically starting the day after infusion and resolving within several days. The cause is unknown but may be related to transient cytokine elevations. Statins' potential to block release of these cytokines has been hypothesized. This study was aimed to evaluate efficacy of acetaminophen and fluvastatin in preventing/reducing post-dose symptoms following ZOL 5 mg infusion. METHODS: Randomized, double-blind, placebo-controlled study of efficacy of acetaminophen or fluvastatin in preventing increases in body temperature or use of rescue medication (ibuprofen) following a single ZOL infusion. Bisphosphonate-naive postmenopausal women with low bone mass (N = 793) were randomized into three treatment groups and given 650 mg acetaminophen or 80 mg fluvastatin or placebo 45 min before ZOL infusion. The acetaminophen group continued taking 650 mg acetaminophen every 6 h over the next 3 days, and the other two groups took matching placebo according to the same schedule. Subjects recorded body temperature, symptoms in a diary. Inflammatory cytokines and C-reactive protein (CRP) were measured at baseline, 24, and 72 h in a study subset. RESULTS: Acetaminophen four times/day significantly reduced the incidence and severity of post-dose symptoms following ZOL infusion. Single-dose fluvastatin 80 mg prior to ZOL infusion did not prevent/reduce post-dose symptoms. Cytokine levels increased by 24 h and returned towards baseline by 72 h, similar to the pattern for post-infusion symptoms. CRP levels increased from baseline to 72 h. CONCLUSIONS: Acetaminophen four times/day for 3 days significantly reduced the incidence and severity of post-dose symptoms following ZOL infusion.