Zometa must only be prescribed and administered to patients by healthcare professionals experienced in the administration of intravenous bisphosphonates. Patients treated with Zometa should be given the package leaflet and the patient reminder card.
Posology
Prevention of skeletal related events in patients with advanced malignancies involving bone
Adults and older people
The recommended dose in the prevention of skeletal related events in patients with advanced malignancies involving bone is 4 mg zoledronic acid every 3 to 4 weeks.
Patients should also be administered an oral calcium supplement of 500 mg and 400 IU vitamin D daily.
The decision to treat patients with bone metastases for the prevention of skeletal related events should consider that the onset of treatment effect is 2-3 months.
Treatment of TIH
Adults and older people
The recommended dose in hypercalcaemia (albumin-corrected serum calcium ≥ 12.0 mg/dl or 3.0 mmol/l) is a single dose of 4 mg zoledronic acid.
Renal impairment
TIH:
Zometa treatment in TIH patients who also have severe renal impairment should be considered only after eva luating the risks and benefits of treatment. In the clinical studies, patients with serum creatinine > 400 µmol/l or > 4.5 mg/dl were excluded. No dose adjustment is necessary in TIH patients with serum creatinine < 400 µmol/l or < 4.5 mg/dl (see section 4.4).
Prevention of skeletal related events in patients with advanced malignancies involving bone:
When initiating treatment with Zometa in patients with multiple myeloma or metastatic bone lesions from solid tumours, serum creatinine and creatinine clearance (CLcr) should be determined. CLcr is calculated from serum creatinine using the Cockcroft-Gault formula. Zometa is not recommended for patients presenting with severe renal impairment prior to initiation of therapy, which is defined for this population as CLcr < 30 ml/min. In clinical trials with Zometa, patients with serum creatinine > 265 µmol/l or > 3.0 mg/dl were excluded.
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).
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Baseline creatinine clearance (ml/min)
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Zometa recommended dose*
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|
> 60
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4.0 mg zoledronic acid
|
|
50–60
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3.5 mg* zoledronic acid
|
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40–49
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3.3 mg* zoledronic acid
|
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30–39
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3.0 mg* zoledronic acid
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* 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 section 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 4.4).
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
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Baseline creatinine clearance (ml/min)
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Remove the following amount of Zometa solution for infusion (ml)
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Replace with the following volume of sterile sodium chloride 9 mg/ml (0,9%), or 5% glucose solution for injection (ml)
|
Adjusted dose (mg zoledronic acid in 100 ml)
|
|
50-60
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12.0
|
12.0
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3.5
|
|
40-49
|
18.0
|
18.0
|
3.3
|
|
30-39
|
25.0
|
25.0
|
3.0
|
Zometa 4 mg/100 ml solution for infusion must not be mixed with other infusion solutions and should be administered as a single intravenous solution in a separate infusion line.
Patients must be maintained well hydrated prior to and following administration of Zometa.
General
Patients must be assessed prior to administration of Zometa to ensure that they are adequately hydrated.
Overhydration should be avoided in patients at risk of cardiac failure.
Standard hypercalcaemia-related metabolic parameters, such as serum levels of calcium, phosphate and magnesium, should be carefully monitored after initiating Zometa therapy. If hypocalcaemia, hypophosphataemia, or hypomagnesaemia occurs, short-term supplemental therapy may be necessary. Untreated hypercalcaemia patients generally have some degree of renal function impairment, therefore careful renal function monitoring should be considered.
Zometa contains the same active substance as found in Aclasta (zoledronic acid). Patients being treated with Zometa should not be treated with Aclasta or any other bisphosphonate concomitantly, since the combined effects of these agents are unknown.
Renal insufficiency
Patients with TIH and evidence of deterioration in renal function should be appropriately eva luated with consideration given as to whether the potential benefit of treatment with Zometa outweighs the possible risk.
The decision to treat patients with bone metastases for the prevention of skeletal related events should consider that the onset of treatment effect is 2–3 months.
Zometa has been associated with reports of renal dysfunction. Factors th
