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Caspofungin (Cancidas), the first approved drug of a new class of antifungal agents called echinocandins (or glucan synthesis inhibitors), was released this year.


Caspofungin, an intravenous medication, is indicated for the treatment of invasive aspergillosis in patients who don't respond to, or can't tolerate, other antifungal therapies such as amphotericin B, lipid formulations of amphotericin B, or itraconazole. The drug hasn't been studied as initial therapy for invasive aspergillosis.



During the past two decades, as the number of people with compromised immune systems rises, the incidence of life-threatening fungal infections like aspergillosis has also increased.


Aspergillosis is caused by the mold Aspergillus, which lives in soil, decaying vegetation, foods, dust, and water. Infections are caused by the inhalation of airborne fungal spores; these spores are cleared from the lungs of most healthy people without affecting their health.


However, Aspergillus can be deadly in hospitalized or immunocompromised patients-those with HIV or AIDS, malignancy, or those who've received an organ or bone marrow transplant. The presence of fungi in the hospital, particularly during times of construction or renovation, is an important source of nosocomial infection. Invasive aspergillosis can spread through the bloodstream to the heart, brain, kidneys, eyes, or other organs. The mortality rate associated with aspergillosis ranges from 50% to more than 90%.



Echinocandins are the first new class of antifungals to be introduced in more than a decade.


Caspofungin acts by inhibiting the synthesis of [latin sharp s] (1,3)-D-glucan, a component of the fungal cell wall. By inhibiting cell wall synthesis, caspofungin blocks the activity of the fungus. Human cells don't have cell walls, thus the drug cannot affect the patient's cells in the same way. Other already available antifungals act by disrupting fungal cell membrane function.



The approval of caspofungin was based on results of a small, multicenter, open-label, noncomparative study of patients with invasive aspergillosis who weren't responding to, or couldn't tolerate, other antifungal therapies.


* Overall, 41% of patients had a favorable response, meaning complete resolution or partial improvement of all signs, symptoms, and radiographic findings.


* Among patients who received caspofungin for more than seven days, 50% had a favorable response.


* Among the subgroups who were unresponsive to or intolerant of previous therapies, 36% and 70%, respectively, had a favorable response.




These drug-related adverse events were reported in clinical trials:


* fever


* phlebitis, thrombophlebitis, or other venous complications


* headache


* nausea or vomiting


* rash


* skin flushing


* liver function test elevations


* anaphylaxis


* pruritus



The drug's labeling advises against administering caspofungin concomitantly with cyclosporine, a drug used frequently in immunocompromised patients, for example, to prevent rejection in post-transplant patients. The combination was shown to result in increases of alanine transaminase (ALT) levels to two to three times the upper limit of normal. FIGURE

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.


Caspofungin is administered as a single 70-mg loading dose on day one, followed by 50 mg once daily thereafter. The drug is administered as a slow intravenous infusion for about one hour. Dosage adjustment is not needed for patients with renal insufficiency, mild hepatic insufficiency, or in the elderly. Patients with moderate hepatic insufficiency, however, should receive only 35 mg daily after the 70-mg loading dose.