Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Bondronat (Hospira)
vials containing 6 mg/6 mL
Approved indications: hypercalcaemia, bony metastases of breast cancer
Australian Medicines Handbook section 10.3.1

Bisphosphonates can reduce the hypercalcaemia of malignant disease by inhibiting the resorption of bone. Clodronate, pamidronate and zoledronic acid are already available for this indication. They are now joined by ibandronic acid which has been approved for patients, with or without metastases, who have tumour-induced hypercalcaemia. It is also approved for the treatment of metastatic bone disease in patients with breast cancer.

When ibandronic acid is given intravenously, it should be diluted and infused over two hours. For hypercalcaemia the dose is determined by the serum calcium, after correction for the albumin concentration. Patients with metastatic breast cancer can be given an intravenous infusion every four weeks or a daily oral dose. Ibandronic acid should not be taken with food as this reduces its bioavailability by 90%. The tablets must be swallowed whole with water and the patient must not lie down for 30 minutes afterwards.

About half of the dose is absorbed by bone. The remainder is excreted unchanged in the urine. No dose adjustment is suggested for hepatic impairment, but the dose should be reduced in patients with severe renal impairment.

A randomised phase II trial studied 174 cancer patients with hypercalcaemia.1These patients were given ibandronic acid in one of three different doses. The best response to treatment was seen in the patients given the highest dose (2 mg). In this group of 55 patients, 37 became normocalcaemic. Patients with higher baseline concentrations of calcium also responded better to the highest dose.

The efficacy of intravenous ibandronic acid, given every 3–4 weeks, was assessed in a placebo-controlled trial of 466 women with breast cancer and bony metastases. Their median time in the study was 13 months with placebo and 18 months with ibandronic acid. Although a 2 mg dose was not statistically different from placebo, the rate of skeletal complications was reduced in women given ibandronic acid 6 mg. At that dose there were 2.65 'bone events' per patient compared with 3.64 in the placebo group. (These events included fractures and other bony complications requiring treatment.) The women taking ibandronic acid 6 mg also had less bone pain.2

Oral ibandronic acid was assessed in 435 women with bony metastases randomised to take 20 mg, 50 mg or a placebo daily for up to 96 weeks. The mean number of bone events per patient was 1.36 with 20 mg, 1.43 with 50 mg and 2.23 with placebo. Although the two doses of ibandronic acid had similar efficacy the higher dose is recommended for clinical use.3

The adverse effects of oral treatment include dyspepsia, oesophagitis, abdominal pain, nausea and hypocalcaemia. Intravenous ibandronic acid is associated with fever or a flu-like illness, asthenia, diarrhoea, vomiting, headache and myalgia. Calcium and renal function should be monitored during treatment. The patient must have an adequate intake of calcium and vitamin D if there is a risk of hypocalcaemia. They should also have a dental check-up before treatment because of the association between bisphosphonates and osteonecrosis of the jaw.

A Cochrane review has concluded that bisphosphonates are effective treatment for the bony metastases of breast cancer, although they have no effect on survival. It did not report if ibandronic acid had a clinical advantage over other bisphosphonates.4An analysis in the UK found that oral ibandronic acid is more cost-effective than intravenous pamidronate or zoledronic acid, but this could reflect the cost of infusions rather than greater efficacy.5Comparative trials are needed.

Read about The Transparency Score Manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.