Zoledronic Acid Fresenius Kabi Dosage/Direction for Use

Zoledronic acid Fresenius Kabi must only be prescribed and administered to patients by healthcare professionals experienced in the administration of intravenous bisphosphonates.
Mode of Administration: Intravenous use.
Zoledronic acid Fresenius Kabi concentrate for solution for infusion contains overfill, allowing for the withdrawal of 5 ml of concentrate (equivalent to zoledronic acid 4 mg). Dilute this concentrate immediately in 100 ml of sterile sodium chloride 0.9% or glucose 5% injection. To avoid inadvertent injection, do not store undiluted concentrate in a syringe. (see Special Precautions for Disposal and Other Handling under Cautions for Usage) Diluted solution should be given as a single intravenous infusion in no less than 20 minutes.
In patients with mild to moderate renal impairment, reduced Zoledronic acid Fresenius Kabi doses are recommended (see Recommended Dose as follows and Precautions).
Instructions for preparing reduced doses of Zoledronic acid Fresenius Kabi: 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.
The withdrawn amount of concentrate must be further diluted in 100 ml of sterile 0.9% w/v sodium chloride solution or 5% w/v glucose solution.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 on less than 20 minutes.
Zoledronic acid Fresenius Kabi 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 Zoledronic acid Fresenius Kabi.
Recommended Dose: Reduction of skeletal related events in patients with advanced malignancies involving bone: Adults and Elderly: The recommended dose in the reduction 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 reduction of skeletal related events should consider that the onset of treatment effect is 2-3 months.
Treatment of TIH: Adults and Elderly: 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: Treatment of TIH: Zoledronic acid Fresenius Kabi 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 (see Precautions).
Reduction of skeletal related events in patients with advanced malignancies involving bone: When initiating treatment with Zoledronic acid Fresenius Kabi 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. Zoledronic acid Fresenius Kabi is not recommended for patients presenting with severe renal impairment prior to initiation of therapy, which is defined for the 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.
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 Zoledronic acid Fresenius Kabi dose is recommended (see Precautions): see Table 1.

Click on icon to see table/diagram/image

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 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 or < 124 µmol/l), an increase of 0.5 mg/dl or 44 µmol/l; for patients with an 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 Precautions). Zoledronic acid Fresenius Kabi 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. From currently available data no recommendation on a posology can be made.