Osteoporosis International

, Volume 23, Issue 2, pp 503–512

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg


    • University of Melbourne Department of Medicine and Bone & Mineral ServiceThe Royal Melbourne Hospital
  • W. Bensen
    • St. Joseph’s Hospital, McMaster University
  • C. Recknor
    • United Osteoporosis Centers
  • O. Ryabitseva
    • Regional Hospital No. 1
  • J. ChiodoIII
    • Otsuka America Pharmaceuticals Inc.
  • P. Mesenbrink
    • Novartis Pharmaceuticals Corporation
  • T. J. de Villiers
    • Panorama MediClinic and Stellenbosch University
Original Article

DOI: 10.1007/s00198-011-1563-8

Cite this article as:
Wark, J.D., Bensen, W., Recknor, C. et al. Osteoporos Int (2012) 23: 503. doi:10.1007/s00198-011-1563-8



Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms.


Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen.


In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion.


The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen.


Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.


AcetaminophenIbuprofenParacetamolZoledronic acid

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011