Zoledronic acid

Class: bisphosphonate – calcium regulator

Indications (NB some may be unlicensed): osteoporosis treatment and prevention, Paget’s disease, prevention of further fracture after hip fracture, hypercalcaemia of malignancy, bone metastases

Contraindications/cautions: renal or hepatic impairment, cardiac impairment, hypo- calcaemic, phosphataemic or magnesaemic patients, administration with diuretics and other nephrotoxic drugs

Adverse reactions: common: hypotension, fatigue, fever and other flu-like symptoms, GI upset (nausea), rash, chest pain, renal toxicity less common: anxiety, insomnia, hypocalcaemia, hypophosphataemia and hypomagnesaemia, sore mouth/throat, eye irritation, conjunctivitis

Metabolism/clearance: excreted unchanged by the kidneys and not metabolised

Interactions:

• additive risk of renal toxicity with other nephrotoxic drugs e.g. frusemide, thalidomide

Syringe driver: not applicable

Mechanism of action: inhibits bone resorption

Onset: hypercalcaemia: 2 to 3 days

Duration: hypercalcaemia: 32 to 39 days bone pain: 4 to 6 weeks

Notes:

• patients must be adequately hydrated before administration of zoledronic acid, especially the elderly and those on diuretics
• renal impairment has been noted after a single administration of the drug. Routinely check serum creatinine clearance pre-administration and cease zoledronic acid if creatinine this is becoming impaired
• osteonecrosis of the jaw has been noted predominantly in adults receiving bisphosphonate infusions
• occasionally severe muscle, bone and joint pain is experienced after infusion, mostly this is relieved after stopping treatment

Malignancy

• in tumour-induced hypercalcaemia if creatinine clearance less than 30 mL/minute seek specialist advice
• in advanced malignancies involving bone:
  • if creatinine clearance greater than 60 mL/minute no dose adjustment required;
  • if creatinine clearance 50 to 60 mL/minute reduce dose to 3.5 mg every 3 to 4 weeks;
  • if creatinine clearance 40 to 50 mL/minute reduce dose to 3.3 mg every 3 to 4 weeks;
  • if creatinine clearance 30 to 40 mL/minute reduce dose to 3 mg every 3 to 4 weeks;
  • avoid if creatinine clearance less than 30 mL/minute;
  • if renal function deteriorates in patients with bone metastases, withhold dose until serum creatinine returns to within 10% of baseline value; see also Cautions above