ZERLINDA Solution for infusion Ref.[50950] Active ingredients: Zoledronic acid

Zerlinda must only be prescribed and administered to patients by healthcare professionals experienced in the administration of intravenous bisphosphonates. Patients treated with Zerlinda 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 serumcalcium ≥12.0mg/dl or 3.0 mmol/l) is a single dose of 4 mg zoledronic acid.

Renal impairment

TIH

Zerlinda treatment in TIH patients 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 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 Zerlinda 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. Zerlinda 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 zoledronic acid, 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 Zerlinda doses are recommended (see also section 4.4).

^* Doses have been calculated assuming target AUC of 0.66 (mg•hr/1) (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 Zerlinda 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, zoledronic acid treatment was resumed only when the creatinine level returned to within 10% of the baseline value (see section 4.4). Zerlinda 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.

Zoledronic acid 4 mg/l00 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 zoledronic acid 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 I below. Remove the volume of Zerlinda solution indicated from the bag 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 Zerlinda 4 mg/100 ml solution for infusion:

Zerlinda 4 mg/1 00 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 Zerlinda.

Clinical experience with acute overdose of zoledronic acid is limited. The administration of doses up to 48 mg of zoledronic acid in error has been reported. Patients who have received doses higher than those recommended (see section 4.2) should be carefully monitored, since renal function impairment (including renal failure) and serum electrolyte (including calcium, phosphorus and magnesium) abnormalities have been observed. In the event of hypocalcaemia, calcium gluconate infusions should be administered as clinically indicated.

Unopened bag: 3 years.

After first opening: Chemical and physical in-use stability has been demonstrated for 24 hours at 2 to 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C.

This medicinal product does not require any special storage conditions.

For storage conditions after first opening of the medicinal product, see section 6.3.

The bags are made of M312A material, a 5-layer, polyolefine based co-extruded film, PVC and plasticizer free. The two tubing ports have spike port tips with a polypropylene cap and a polypropylene injection point with a polypropylene breakable cap.

The bag is supplied with a polyester alox/polypropylene over-wrapping.

Pack size:

1 × 100 ml bag

10 × 100 ml bag

Not all pack sizes may be marketed.

Additional information on handling of Zerlinda, including guidance on the preparation of reduced doses using the Zerlinda infusion bag, is provided in section 4.2.

Aseptic techniques must be followed during the preparation of the infusion. For single use only.

The refrigerated solution should be equilibrated to room temperature prior to administration.

Only clear solution free from particles and discolouration should be used.

Healthcare professionals are advised not to dispose of unused Zerlindavia the domestic sewage system.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.