Published: 10 June 2015

Adverse Reactions Following Zoledronic Acid Infusion

Prescriber Update 36(2): 29
June 2015

Key Messages

  • Patients who are treated with zoledronic acid can experience acute phase reactions.
  • Symptoms include fever, diffuse musculoskeletal pain, gastrointestinal effects, and eye inflammation.
  • The risk of renal reactions can be prevented by keeping patients adequately hydrated prior to and following infusions.

Acute Phase Reactions

Zoledronic acid (marketed as Aclasta and Zometa in New Zealand) is a bisphosphonate administered to patients by intravenous infusion. Prescribers are reminded that patients may experience an acute phase response or adverse effects on renal function following administration.

Acute phase reactions may present with the following symptoms: chills, fever, influenza-like symptoms, night sweats, rigors and shivering, diffuse musculoskeletal pain, gastrointestinal effects, and eye inflammation1.

Acute phase responses can occur at any time up to approximately two weeks following an infusion1. The majority of patients will experience symptoms within the first three days after an infusion1. These reactions are usually self-limiting and resolve completely within 24 to 48 hours2. However, in some patients symptoms may persist for longer periods.

Supportive and symptomatic management with paracetamol and non-steroidal anti-inflammatory drugs is recommended, once other serious causes of fever such as infection have been excluded2. Pre-treatment with paracetamol or ibuprofen may also be helpful for some patients2.

Renal Reactions

Renal reactions can also occur shortly after infusion. Adequate hydration can help to reduce the risk of renal deterioration after a zoledronic acid infusion4–6. Renal deterioration, progression to renal failure and dialysis has been reported in patients following the initial dose of zoledronic acid5.

If patients show signs of renal function decline after infusion, the benefits and risks of harm of continued treatment should be evaluated.

Factors which may increase the risk of renal deterioration following zoledronic acid infusions are:

Bisphosphonates are also associated with ocular inflammatory effects such as uveitis and scleritis3. Ocular complications are uncommon. However, patients should be advised to seek immediate medical attention if they experience any ocular symptoms while being treated with a bisphosphonate.

The Centre for Adverse Reaction Monitoring (CARM) has received 153 reports of musculoskeletal adverse reactions starting within one month after a zoledronic acid infusion. CARM also received 26 reports of ocular adverse reactions and 33 reports of urinary adverse reactions within one month following an infusion.

Healthcare professionals are encouraged to report all suspicions of medicine adverse reactions to CARM.

  1. Reid IR, Gamble GD, Mesenbrink P, et al. 2010. Characterization of and risk factors for the acute-phase response after zoledronic acid. The Journal of Clinical Endocrinology and Metabolism 95: 4380–4387.
  2. Tanvetyanon T, Stiff PJ. 2006. Management of the adverse effects associated with intravenous bisphosphonates. Annals of oncology 17: 897–907.
  3. Medsafe. 2011. Reminder: Keeping an eye on bisphosphonates. Prescriber Update 32(3): 24. URL: (accessed 19 May 2015).
  4. Attivi D, Kosmalski G, Zeghmouli C, et al. 2014. Effect of intravenous hydration in patients receiving bisphosphonate therapy. International Journal of Clinical Pharmacy 36: 1277–1281.
  5. Novartis New Zealand Limited. 2014. Zometa Data Sheet. 21 October 2014. URL: (accessed 19 May 2015).
  6. Novartis New Zealand Limited. 2014. Aclasta Data Sheet. 8 October 2014. URL: (accessed 19 May 2015).