ZOLETEM CONCENTRATE FOR SOLUTION FOR INFUSION 4MG/5ML [SIN15982P]

Product Info

ZOLETEM CONCENTRATE FOR SOLUTION FOR INFUSION 4MG/5ML

[SIN15982P]

Indication

INDICATIONS

• Treatment of osteolytic, osteoblastic, and mixed bone metastases of solid tumours and osteolytic lesions of multiple myeloma, in conjunction with standard antineoplastic therapy.

• Treatment of hypercalcemia of malignancy (HCM).

Dosing

DOSAGE REGIMEN AND ADMINISTRATION

The Zoletem 4 mg/5 mL concentrate for solution for infusion should be further diluted with 100 mL 0.9% sodium chloride injection or 5% dextrose injection before infusion (see section INSTRUCTIONS FOR USE AND HANDLING – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The final Zoletem solution for infusion, should be given as an intravenous infusion of no less than 15 minutes.

Dosage regimen
Treatment of bone metastases and treatment of osteolytic lesions, in conjunction with standard antineoplastic therapy
In adults and elderly patients, the recommended Zoletem dose is a 4 mg infusion given every 3 to 4 weeks.
Patients should also be administered an oral calcium supplement of 500 mg and 400 international units vitamin D daily.

Treatment of hypercalcemia of malignancy (HCM)
In adult and elderly patients, the recommended Zoletem dose in hypercalcemia (albumin-corrected serum calcium ≥ 12.0 mg/dL or 3.0 mmol/L) is a single 4 mg infusion. Patients must be maintained well hydrated prior to and following administration of Zoletem.

Treatment of patients with renal impairment
Patients with hypercalcemia with malignancy (HCM)
Zoletem treatment in adult patients with hypercalcemia of malignancy (HCM) who also have severe renal impairment should be considered only after evaluating the risks and benefit of treatment. In the clinical studies, patients with serum creatinine >400 micromol/L or >4.5 mg/dL were excluded. No dose adjustment is necessary in HCM patients with serum creatinine < 400 micromol/L or < 4.5 mg/dL (see section SPECIAL WARNINGS AND PRECAUTIONS FOR USE – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Treatment of bone metastases and treatment of osteolytic lesions, in conjunction with standard antineoplastic therapy.
When initiating treatment with Zoletem, serum creatinine levels and creatinine clearance (CL_cr) should be determined. CL_cr is calculated from serum creatinine levels using the Cockcroft-Gault formula. Zoletem is not recommended for patients presenting with severe renal impairment prior to initiation of therapy, which is defined for this population as CL_cr < 30 mL/min. In clinical trials with Zoletem, patients with serum creatinine > 265 micromol/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 CrCl 30 to 60 mL/min, the following Zoletem dose is recommended (see also section SPECIAL WARNINGS AND PRECAUTIONS FOR USE – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):

Following initiation of therapy, serum creatinine should be measured prior to each dose of Zoletem 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), an increase of ≥ 0.5 mg/dL;

• For patients with an abnormal baseline creatinine (< 1.4 mg/dL), an increase of ≥ 1.0 mg/dL.

In the clinical studies, Zoletem treatment was resumed only when the creatinine level returned to within 10% of the baseline value (see section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Zoletem should be resumed at the same dose as that prior to treatment interruption.

Method of administration
Zoletem must only be administered to patients by healthcare professionals experienced in the administration of intravenous bisphosphonates.
Zoletem 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 line separate from all other drugs in no less than 15 minutes.
Patients must be maintained in a well hydrated state prior to and following administration of Zoletem.

Preparation of reduced Zoletem doses
In patients with mild to moderate renal impairment, which is defined as CL_cr 30 to 60 mL/min, reduced Zoletem dosages are recommended, except in patients with HCM (see section Dosage regimen sub-section).
To prepare reduced doses of Zoletem 4 mg/5 mL concentrate, withdraw an appropriate volume of the liquid 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 information on the reconstitution and dilution of Zoletem (see section INSTRUCTIONS FOR USE AND HANDLING – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The withdrawn amount of the concentrate must be diluted in 100 mL of sterile 0.9% sodium chloride injection or 5% dextrose injection. The dose must be given as a single intravenous infusion of no less than 15 minutes.

Contraindications

CONTRAINDICATIONS

• Hypersensitivity to zoledronic acid or other bisphosphonates or any of the excipients in the formulation of Zoletem.

• Pregnancy and breast-feeding women (see section PREGNANCY, LACTATION, FEMALES AND MALES OF REPRODUCTIVE POTENTIAL – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).