Introduction

Caspofungin is the first of a new class of antifungal drug, the echinocandins, to be licensed. It is intravenous only, very active against Candida and also active against Aspergillus. It has essentially no activity other than these two groups of pathogens.

Dose & Delivery

Caspofungin is intravenous only. The standard dose is a 70mg loading dose with each subsequent dose being 50mg, each given once a day. In patients weighing more than 80kg it is recommended that 70mg a day is given rather than 50mg a day. Patients with moderate liver insufficiency should receive a dose of 35mg a day and it is possible that the drug is not appropriate for patients with severe liver disease although this has not been decided. The drug is not licensed for use in children, although it is likely that the dose of 50mg/m 2 daily will be appropriate.

Fungi the drug is active against.

Caspofungin is active against all species of Candida. It is extremely active against all species except Candida parapsilosis, Candida guilliermondii and Candida lusitaniae against which it is moderately active. For over 90% of these isolates it is fungicidal in-vitro and models have demonstrated fungal killing in vivo. It is also active in patients against isolates to which the drug is slightly less active but it may be that either larger doses or alternative regiments would be required for patients with very difficult to treat disease with these organisms such as heart valve or eye infections.

Typical regimens

70mg, loading dose then 50mg a day, increased for people weighing over 80mg.

Metabolism and excretion

The drug is chemically degraded slowly in the body. This happens probably in multiple organs including the liver. As a result there are very few alterations to be made in patients with organ dysfunction or taking other drugs with the one exception of severe liver dysfunction.

Drug/Drug interactions

Caspofungin is not an inhibitor and is a poor substrate for cytochrome people P450 enzymes. It is not a substrate for P-glycoprotein. Concomitant use of cyclosporin with caspofungin increases the exposure to caspofungin by about a third. Caspofungin reduces the trough concentration of tacrolimus by about a quarter so in both instances monitoring of these drugs is appropriate. Concomitant use of caspofungin with rifampicin increases caspofungin exposure but this changes over the first two weeks of therapy. It is likely that strong enzyme inducers such as efavirenz and nevirapine, rifampicin, dexamethasome, phenytoin or carbamazepine may require a slight increase in caspofungin doses, typically 70mg a day.

Side effects

Phlebitis was the commonest side effect in patients receiving caspofungin through a peripheral intravenous catheter. Fever, elevated liver function tests, abdominal pain, nausea, diarrhoea and vomiting were all common together with headache. All were mild and/or reversible when the drug was stopped. Other side effects appeared to be rare.

Other information

Long term side effects have not been established with the echinocandins because they are relatively new compounds. The duration of therapy is uncertain but typically should be at least two weeks beyond the last evidence of active disease unless a switch to another antifungal is made.