Zoledronic acid

CLINICAL USE

Hypercalcaemia of malignancy Reduction of bone damage in advanced malignancies Paget’s disease

DOSE IN NORMAL RENAL FUNCTION

Hypercalcaemia of malignancy: 4 mg as a single dose Reduction of bone damage in advanced malignancies: 4 mg every 3–4 weeks Paget’s disease: 5 mg as a single dose

PHARMACOKINETICS

Molecular weight : 272.1

%Protein binding : 56

%Excreted unchanged in urine : 39 +/– 16

Volume of distribution (L/kg) : 6.1–10.8 litres

half-life – normal/ESRD (hrs) : 146/Increased

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

>60 Dose as in normal renal function 50–60 3.5 mg 40–49 3.3 mg 30–39 3 mg <29 Use 3 mg with caution if benefit outweighs risk

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD : Unknown dialysability. Dose as in GFR<29 mL/min

HD : Unknown dialysability. Dose as in GFR<29 mL/min

HDF/high flux : Unknown dialysability. Dose as in GFR<29 mL/min

CAV/VVHD : Unknown dialysability. Dose as in GFR=30–39 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs Other nephrotoxic drugs: use with caution as can enhance nephrotoxicity

ADMINISTRATION

Reconstition

Add 5 mL of water for injection to each 4 mg vial

Route

Rate of Administration

15 minutes

Comments

Add to 100 mL sodium chloride 0.9% or glucose 5% Reconstituted solutions are stable for 24 hours at room temperature

OTHER INFORMATION

Also administer a calcium supplement of 500 mg daily plus 400 IU of vitamin D daily Increased risk of renal deterioration if GFR <10 mL/min – measure creatinine while on zoledronic acid Increased risk of renal impairment in older patients, smokers, previous pamidronate therapy and renal failure. (Oh WK, Proctor K, Nakabayashi M. The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid. Cancer. 2007, Mar 15; 109(6): 1090–6.) Incidence of acute renal failure is 10.7%, usually due to acute tubular necrosis. (Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med. 2003; 349(17): 1679–9.) Increased risk of renal failure if use 8 mg May cause osteonecrosis of the jaw .

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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