Sodium clodronate

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Bonefos (Rhone-Poulenc Rorer)
400 mg capsules
ampoules containing 300 mg/5 mL

Indication: hypercalcaemia of malignancy
Malignant tumours can cause hypercalcaemia either by a direct effect on bone or by affecting bone metabolism. Hypercalcaemia can cause a variety of problems ranging from fatigue to renal insufficiency and cardiac arrhythmias. Patients with hypercalcaemia of malignancy often die within a few months. Bisphosphonates such as clodronate can control the hypercalcaemia by reducing bone resorption.

Although oral formulations of clodronate are available, they have a low bioavailability (1-2%) and absorption is negligible if the dose is taken with food. Most patients will be given clodronate intravenously. This requires a daily infusion, over at least two hours, repeated until the serum calcium is normal. Usually normocalcaemia is achieved in 2-5 days.

Clodronate is not metabolised and most of the dose appears in the urine within a few days. Patients must be adequately hydrated before treatment and renal function must be monitored. The terminal elimination half-life may exceed a year as clodronate bound to bone is slowly released.

Adverse reactions include renal insufficiency and hypocalcaemia. The oral formulations can also have adverse effects on the gut.

Clodronate has been compared with pamidronate, a bisphosphonate also approved for treating the hypercalcaemia of malignancy. Both drugs are effective, but the duration of normocalcaemia was 14 days for clodronate and 28 days for pamidronate.1