Posology : מינונים

4.2    Posology and method of administration

Zomera must only be prescribed and administered to patients by healthcare professionals experienced in the administration of intravenous bisphosphonates. Patients treated with Zomera should be given the package leaflet.

Posology
Multiple Myeloma and bone metastases from solid tumors
Adults and older people
The recommended dose 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 hypercalcemia of malignancy (HCM)
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.

Patients must be maintained well hydrated prior to and following administration of Zomera.
ZOM CON API NOV16 CL V10                                                           EU SmPC 06.2016 Renal impairment
Patients with hypercalcemia of malignancy (HCM):
Zomera treatment in patients with hypercalcemia of malignancy (HCM) who also have severe renal impairment should be considered only after evaluating 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 HCM patients with serum creatinine < 400 µmol/l or < 4.5 mg/dl (see section 4.4).

Multiple Myeloma and bone metastases from solid tumors:
When initiating treatment with Zomera in adult 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. Zomera 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 Zomera, patients with serum creatinine > 265 µmol/l or > 3.0 mg/dl were excluded.

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, the following Zomera dose is recommended (see also section 4.4):

Baseline creatinine clearance (ml/min)                   Zomera 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 Zomera 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, Zomera treatment was resumed only when the creatinine level returned to within 10% of the baseline value (see section 4.4). Zomera 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.
Zomera 4 mg concentrate for solution for infusion, further diluted in 100 ml (see section 6.6), should be given as a single intravenous infusion in no less than 15 minutes.

In patients with mild to moderate renal impairment, reduced Zomera doses are recommended (see section “Posology” above and section 4.4).


ZOM CON API NOV16 CL V10                                                              EU SmPC 06.2016 Instructions for preparing reduced doses of Zomera
Withdraw an appropriate volume of the concentrate needed, as follows: -      4.4 ml for 3.5 mg dose
-      4.1 ml for 3.3 mg dose
-      3.8 ml for 3.0 mg dose

For instructions on the dilution of the medicinal product before administration, see section 6.6. The withdrawn amount of concentrate must be further diluted in 100 ml of sterile 0.9% w/v sodium chloride solution or 5% w/v glucose solution. The dose must be given as a single intravenous infusion over no less than 15 minutes.

Zomera concentrate must not be mixed with calcium or other divalent cation-containing infusion solutions such as lactated Ringer’s solution, 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 Zomera.