Orthopaedics  |  Fragility Fracture Pathway - Zoledronic Acid

Special authority required*

Consider as an alternative to oral bisphosphonates if absorption or adherence or ability to follow oral administration instructions are an issue (e.g. in dementia, cognitive impairment, memory loss),or in severe GI disease e.g. acute oesophageal/gastric inflammation or ulceration, oesophageal strictures, achalasia, scleroderma.

Intravenous bisphosphonate

Zoledronate is an IV bisphosphonate that reduces risk of hip, vertebral and non-vertebral fractures. In the pivotal clinical trials, Zoledronate was administered annually for three years. However, Zoledronate’s duration of action is considerably longer than one year; therefore, it is common practice to administer the three initial doses at intervals of 18 or 24 months.

Contraindications to Zoledronate include: creatinine clearance or eGFR <35 mL/min; marked vitamin D deficiency; and hypocalcaemia.

The most common side effect of Zoledronate is post-dose flu-like symptoms (affecting approximately 30% of patients), the majority of which occur within the first 3 days following Zoledronate administration and resolve within 3 days. The incidence of these symptoms can be reduced with administration of paracetamol shortly after the Zoledronate dose. These symptoms decrease markedly with subsequent doses of Zoledronate (incidence of 1–2%). Ensure adequate hydration.

Vitamin D deficiency should be corrected before the administration of Zoledronate. In patients with suspicion of vitamin D deficiency, give oral supplementation (2 x cholecalciferol 50,000 IU) before infusion.

Consider a dose reduction (e.g. to 2.5 or 1 mg) or slower infusion rate (e.g. to 30 to 60 mins) in patients with eGFR 35–50 mL/min.

Dose: 5mg IV over at least 30 minutes, given once a year for 3 years. Less frequent dosing may be possible for many patients. Clinical practice is continuing to evolve as further evidence becomes available on the fracture prevention efficacy with longer intervals between doses. Options include 18-24 month dose intervals, annual infusions for high risk patients, and a single infusion for older patients with limited life expectancy.

NB: IV only, patients must pay an IV administration fee (GP practices differ, ranges from $80-$200)

Renal Function and Hydration:

• Clcr > 50ml/min: Administer standard Zoledronic acid dose.
• Dose reduction may be considered e.g. for very low body weight and/or variable renal function e.g. 35-50ml/min.
  
• Clcr < 35ml/min: Do not administer Zoledronic acid. Contraindications to Zoledronate include: creatinine clearance or eGFR <35 mL/min.
• Withhold diuretics and NSAIDs the morning of infusion to help prevent renal impairment.
• Advise patients to drink an extra 2 glasses of fluid on day of infusion to ensure good hydration.

Replenish vitamin D if necessary:

Vitamin D stores must be adequate before administering IV zoledronic acid (Aclasta®) and serum calcium must be in the normal range.

• If not already receiving vitamin D (colecalciferol), give ONE or TWO 1.25mg capsules of colecalciferol (VitD3) over the week prior to infusion.
• Continue vitamin D supplementation by prescribing ONE capsule of 1.25mg (50,000IU) colecalciferol once a month as maintenance therapy.
• There is no need to measure Vitamin D levels.

Administration:

• Zoledronic acid comes ready to administer, in 100mls of sodium chloride 0.9%.
• Using a metriset, prime tubing carefully to minimise loss.
• Insert I.V. line and withdraw blood sample if required.
• Infuse contents of chamber over 30 minutes and on completion flush line with a further 20mls sodium chloride 0.9% through chamber.

• Patient information
• Patient Consent form
• IV administration checklist and guide

See also:

• Zoledronic acid (NZ Formulary)
• Aclasta® (Medsafe datasheet)

*Find the 'Zoledronic acid inj 0.05 mg per ml, 100ml' Special Authority Form under the 'Musculoskeletal System' heading on the Pharmac 'Special Authority Forms' webpage.