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.
Cancidas (Merck Sharp and Dohme)
vials containing 50 mg or 70 mg as lyophilised powder
Approved indication: aspergillosis
Australian Medicines Handbook section: 5.2
Immunosuppressed patients, including patients treated with large doses of corticosteroids, are at risk of invasive aspergillosis. They are usually treated with amphotericin. If this does not work then caspofungin can be considered.
Caspofungin is from a new class of drugs which inhibit the synthesis of the glucan component of the fungal cell wall. Although caspofungin is active against species of candida it is only approved for aspergillosis as this was the indication that was granted fast-track approval by the Food and Drug Administration in the USA.
The drug is reconstituted in 0.9% saline or water for injection then given by slow intravenous infusion. A loading dose is given on the first day. On the following days a smaller single dose is given by infusion until the patient improves. Caspofungin is slowly metabolised with only small amounts appearing unchanged in the urine. The dose should be reduced in patients with hepatic impairment.
As caspofungin is reserved for patients who are refractory to or intolerant of other antifungal drugs, its approval has been based on only 58 patients with invasive aspergillosis. Most of the patients had a haematological malignancy or had received a transplant. There was a favourable response in 34% of the people who were refractory to other drugs. Responses were lower in patients with extra pulmonary aspergillosis.
Common adverse reactions in the study included nausea, vomiting, fever and flushing. Some patients developed complications such as phlebitis at the site of infusion. Caspofungin can decrease haemoglobin and increase liver enzyme concentrations. It should not be prescribed with cyclosporin because of the risk of altered hepatic function.
Although only a minority of patients will respond, this is a better outcome than could be expected for patients who are refractory to other drugs. It is unknown if resistance to caspofungin will develop.