For patients with normal renal function (defined as CLcr > 60 ml/min), zoledronic acid 4 mg/100 ml solution for infusion may be administered directly without any further preparation. In patients with bone metastases presenting with mild to moderate renal impairment prior to initiation of therapy, which is defined for this population as CLcr 30–60 ml/min, reduced Zometa doses are recommended (see also section 4.4).

Baseline creatinine clearance (ml/min)
 Zometa recommended dose*
 
> 60
 4.0 mg zoledronic acid
 
50–60
 3.5 mg* zoledronic acid
 
40–49
 3.3 mg* zoledronic acid
 
30–39
 3.0 mg* zoledronic acid
 

* Doses have been calculated assuming target AUC of 0.66 (mg•hr/l) (CLcr = 75 ml/min). The reduced doses for patients with renal impairment are expected to achieve the same AUC as that seen in patients with creatinine clearance of 75 ml/min.

Following initiation of therapy, serum creatinine should be measured prior to each dose of Zometa and treatment should be withheld if renal function has deteriorated. In the clinical trials, renal deterioration was defined as follows:

- For patients with normal baseline serum creatinine (< 1.4 mg/dl or < 124 µmol/l), an increase of 0.5 mg/dl or 44 µmol/l;

- For patients with abnormal baseline creatinine (> 1.4 mg/dl or > 124 µmol/l), an increase of 1.0 mg/dl or 88 µmol/l.

In the clinical studies, Zometa treatment was resumed only when the creatinine level returned to within 10% of the baseline value (see section 4.4). Zometa treatment should be resumed at the same dose as that given prior to treatment interruption.

Paediatric population

The safety and efficacy of zoledronic acid in children aged 1 year to 17 years have not been established. Currently available data are described in sections 4.4 and 5.1 but no recommendation on a posology can be made.

Method of administration

Intravenous use.

Zometa 4 mg/100 ml solution for infusion should be given as a single intravenous infusion in no less than 15 minutes.

In patients with normal renal function, defined as CLcr > 60 ml/min, zoledronic acid 4 mg/100 ml solution for infusion must not be further diluted.

In patients with mild to moderate renal impairment, reduced Zometa doses are recommended (see section “Posology” above and section 6.3).

To prepare reduced doses for patients with baseline CLcr  60 ml/min, refer to Table 1 below. Remove the volume of Zometa solution indicated from the bottle and replace with an equal volume of sterile sodium chloride 9 mg/ml (0,9%) solution for injection, or 5% glucose solution for injection.

Table 1: Preparation of reduced doses of Zometa 4 mg/100 ml solution for infusion

Baseline creatinine clearance (ml/min)