title: Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.
abstract: CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.
authors.affiliation: University of Melbourne Department of Medicine and Bone & Mineral Service, The Royal Melbourne Hospital, Melbourne, 3050 Victoria, Australia. jdwark@unimelb.edu.au
authors.forename: J D
authors.initials: JD
authors.lastname: Wark
authors.forename: W
authors.initials: W
authors.lastname: Bensen
authors.forename: C
authors.initials: C
authors.lastname: Recknor
authors.forename: O
authors.initials: O
authors.lastname: Ryabitseva
authors.forename: J
authors.initials: J
authors.lastname: Chiodo
authors.forename: P
authors.initials: P
authors.lastname: Mesenbrink
authors.forename: T J
authors.initials: TJ
authors.lastname: de Villiers
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000368:Aged; D018771:Arthralgia / Q000139:chemically induced / Q000517:prevention & control; D001831:Body Temperature / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D006261:Headache / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000082:Acetaminophen; D000077211:Zoledronic Acid; D007052:Ibuprofen