Zoltero 4 Dosage/Direction for Use

The Zoledronic acid 4 mg/5 mL concentrate should be further diluted with 100 mL 0.9% w/v sodium chloride or 5% w/v glucose solution before infusion (see Instructions for Use and Handling under Cautions for Usage). The final Zoledronic acid solution for infusion, should be given as an intravenous infusion of no less than 15 minutes.
The Zoledronic acid 4 mg/100 mL solution for infusion is a "ready to use" presentation and must not be further diluted or mixed with other infusion solutions except for patients with renal impairment. It should be administered as a single intravenous solution in a separate infusion line in no less than 15 minutes.
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Treatment of bone metastases and treatment of osteolytic lesions, in conjunction with standard antineoplastic therapy: In adults and elderly patients, the recommended Zoledronic acid 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 IU vitamin D daily.
Treatment of hypercalcemia of malignancy (HCM): In adult and elderly patients, the recommended Zoledronic acid dose in hypercalcaemia (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 Zoledronic acid.
Treatment of patients with renal impairment: Patients with hypercalcemia with malignancy (HCM): Zoledronic acid treatment in adult patients with hypercalcaemia 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 Precautions).
Treatment of bone metastases and treatment of osteolytic lesions, in conjunction with standard antineoplastic therapy: When initiating treatment with Zoledronic acid, serum creatinine levels and creatinine clearance (CL_cr) should be determined. CL_cr is calculated from serum creatinine levels using the Cockcroft-Gault formula. Zoledronic acid 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 Zoledronic acid, 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 Zoledronic acid dose is recommended (see also Precautions): (See Table 5.)

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Following initiation of therapy, serum creatinine should be measured prior to each dose of Zoledronic acid 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, Zoledronic acid treatment was resumed only when the creatinine level returned to within 10% of the baseline value (see Precautions). Zoledronic acid should be resumed at the same dose as that prior to treatment interruption.
Method of administration: Zoledronic acid must only be administered to patients by healthcare professionals experienced in the administration of intravenous bisphosphonates.
Zoledronic acid 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 Zoledronic acid.
Preparation of reduced Zoledronic acid doses: In patients with mild to moderate renal impairment, which is defined as CLcr 30 to 60 mL/min, reduced Zoledronic acid dosages are recommended, except in patients with HCM (see Dosage & Administration as previously mentioned).
To prepare reduced doses of Zoledronic acid 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 Zoledronic acid (see Instructions for Use and Handling under Cautions for Usage). The withdrawn amount of the concentrate must be 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 of no less than 15 minutes.
To prepare reduced doses of Zoledronic acid 4 mg/100 mL solution for infusion remove the corresponding volume of Zoledronic acid solution as indicated as follows and replace it with an equal volume of sterile 0.9% w/v sodium chloride solution or 5% w/v glucose solution. (See Table 6.)

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