Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Atnahs Pharma Netherlands B.V., Strawinskylaan 3127, 1077 ZX Amsterdam, Netherlands
Bondronat is indicated in adults for
Patients treated with Bondronat should be given the package leaflet and the patient reminder card. Bondronat therapy should only be initiated by physicians experienced in the treatment of cancer.
The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenous injection given every 3-4 weeks. The dose should be infused over at least 15 minutes.
A shorter (i.e. 15 min) infusion time should only be used for patients with normal renal function or mild renal impairment. There are no data available characterising the use of a shorter infusion time in patients with creatinine clearance below 50 ml/min. Prescribers should consult the section Patients with Renal Impairment (see section 4.2) for recommendations on dosing and administration in this patient group.
Prior to treatment with Bondronat the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium chloride solution. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In general patients with osteolytic bone metastases require lower doses than patients with the humoral type of hypercalcaemia. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥3 mmol/l or ≥12 mg/dl) 4 mg is an adequate single dose. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy.
* Note albumin-corrected serum calcium concentrations are calculated as follows:
Albumin-corrected serum calcium (mmol/l) = serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8
Or
Albumin-corrected serum calcium (mg/dl) = serum calcium (mg/dl) + 0.8 x [4 – albumin (g/dl)]
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4.
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (return of albumin-corrected serum calcium to levels above 3 mmol/l) was 18-19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.
Bondronat concentrate for solution for infusion should be administered as an intravenous infusion over 2 hours.
No dose adjustment is required (see section 5.2).
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no doseadjustment is necessary. For patients with moderate renal impairment (CLcr ≥30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed (see section 5.2):
| Creatinine Clearance (ml/min) | Dosage | Infusion Volume1 and Time2 |
|---|---|---|
| >50 CLcr <80 | 6 mg (6 ml of concentrate for solution for infusion) | 100 ml over 15 minutes |
| >30 CLcr <50 | 4 mg (4 ml of concentrate for solution for infusion) | 500 ml over 1 hour |
| <30 | 2 mg (2 ml of concentrate for solution for infusion) | 500 ml over 1 hour |
1 0.9% sodium chloride solution or 5% glucose solution
2 Administration every 3 to 4 week
A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.
No dose adjustment is required (see section 5.2).
The safety and efficacy of Bondronat in children and adolescents below the age of 18 years have not been established. No data are available (see section 5.1 and section 5.2).
For intravenous administration.
The content of the vial is to be used as follows:
For single use only. Only clear solution without particles should be used.
Bondronat concentrate for solution for infusion should be administered as an intravenous infusion. Care must be taken not to administer Bondronat concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage..
Up to now there is no experience of acute poisoning with Bondronat concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored. Clinically relevant hypocalcaemia should be corrected by intravenous administration of calcium gluconate.
5 years.
After reconstitution: 24 hours.
This medicinal product does not require any special storage conditions prior to reconstitution.
After reconstitution: Store at 2°C–8°C (in a refrigerator).
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, unless reconstitution has taken place in controlled and validated aseptic conditions.
Bondronat is supplied as packs containing 1, 5 and 10 vials (6 ml type I glass vial with a bromobutyl rubber stopper). Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
The release of pharmaceuticals in the environment should be minimized.
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