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.
Zometa (Novartis)
vials containing 4 mg as dry powder
Approved indication: tumour-induced hypercalcaemia
Australian Medicines Handbook Section 10.4.2
Zoledronic acid is a bisphosphonate with a hydroxyl group and an imidazoleside chain. This structure makes zoledronate a potent inhibitor of osteoclasticbone resorption. (See 'Bisphosphonates - mechanisms of action' Aust Prescr 2000;23:130-2).
Bone resorption is an important cause of the hypercalcaemia seen in some cancers. Rehydration and bisphosphonates such as clodronate and pamidronate can therefore be used to return calcium concentrations to normal. As zoledronic acid is amore potent bisphosphonate it may give improved results.
Clinical trials have compared a five-minute infusion of zoledronic acid with a two-hour infusion of pamidronate. Ten days after the infusion approximately 88% of patients with tumour-induced hypercalcaemia had responded to zoledronic acid while 70% had responded to pamidronate.
The median time for patients to relapse is significantly longer after zoledronic acid (30 days versus 17 days for pamidronate). This may be related to its long half-life of 167 hours. The drug is excreted unchanged in the urine so it is not recommended for patients with severe renal impairment.
In patients with cancer adverse events are common. Adverse reactions that have been attributed to zoledronic acid include nausea, fever and itching. Hypocalcaemia will occur in 6% of patients. If this is symptomatic the patient may need to be given calcium gluconate. Renal function should be monitoredas it can be impaired by bisphosphonates. This risk may be reduced by giving the infusion over 15 minutes.
Zoledronic acid is an effective treatment, but it is less effective once the patient has relapsed. Retreatment with a higher dose has a response rate of 52%. Patients who are refractory to the first dose should not be retreated for at least a week. As zoledronic acid also has some antitumour effects it is being studied in patients with bony metastases or myeloma.
