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Caspofungin Acetate

Pham, Paul Pharm D

Infectious Diseases in Clinical Practice: June-July 2001 - Volume 10 - Issue 5 - p 282-283
SPECIAL ARTICLES: PROFILES ON NEW DRUGS
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Division of Infectious Diseases, Johns Hopkins University School of Medicine

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Caspofungin Acetate

Brand name/manufacturer: Cancidas®/Merck

Class: Echinocandin antifungal

Formulation: 50 mg and 70 mg IV vial (reconstitute with normal saline only)

Price: $371.00 for 70-mg vial and $288.00 for 50-mg vial

Dose: 70 mg IV load on day 1, then 50 mg IV qd (infuse over 1 hour)

Dose for renal insufficiency: Usual dose recommended. Not dialyzable, thus no supplemental doses needed postdialysis.

Dose for hepatic insufficiency: For Child-Pugh score of 7–9, after initial 70-mg load on day 1, decrease daily dose to 35 mg qd.

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Pharmacology:

Mechanism of Action: Beta (1,3)-d-glucan is an integral component of fungal cell wall, is inhibited by caspofungin.

Distribution: Well distributed into tissues by 36–48 hours. Protein binding (97%)

Metabolism: Metabolized by N-acetylation and hydrolysis. Spontaneous chemical degradation.

Excretion: 35% and 41% of metabolites are excreted in the feces and urine respectively. Only 1.4% of unchanged drug is excreted in the urine. Half-life (beta-phase) of 9–11 hours.

Drug interactions: Caspofugin did not induce or inhibit the cytochrome P450 system. Cyclosporin increased caspofugin AUC by 35% (co-administration not recommended, close monitoring of liver enzyme recommended with co-administration). Tacrolimus AUC decreased by 20% with caspofugin co-administration (monitor tacrolimus levels closely).

Adverse reactions: Generally well tolerated. Histamine-mediated symptoms, including rash, facial swelling, pruritus, and sensation of warmth, have been reported. Other side effects associated with caspofugin include fever, phlebitis, nausea, vomiting, headache, eosinophilia, proteinuria, increased alkaline phosphatase, and hypokalemia.

Pregnancy: Category C. No human data. Animal data with exposure similar to a 70-mg dose in human resulted in incomplete ossification of skull, torso, cervical ribs, and talus/calcaneous.

FDA indication: Treatment of invasive aspergillosis in patients who are refractory or intolerant to other antifungal therapy.

Spectrum of activity: Aspergillus fumigatus, A. flavus, A. terreus; C. albican, C. tropicalis, C. glabrata, C. lusitaniae, C. parapsilosis, C. krusiei; no activity against C. neoformans.

Clinical trials: Caspofugin (70-mg loading dose on day 1, then 50 mg qd) was given to 69 patients with invasive aspergillosis in an open-label, noncomparative study. Of these 69 patients, 53 (84%) were refractory to previous antifungal therapy and 10 (16%) were intolerant. For those patients who received at least one dose of caspofugin, 41% (26/63) had a favorable response (defined by an expert panel as either complete resolution or clinically meaningful improvement of all signs and symptoms and attributed radiologic findings). Favorable response to caspofugin for either refractory or intolerant to previous therapy was 36% (19/53) and 70% (7/10), respectively.

Comments: Caspofugin offers clinicians a welltolerated and cost-effective alternative to liposomal amphotericin for the treatment of invasive aspergillosis that is refractory or intolerant to other antifungal therapy. Though it does not have the FDA indication, caspofugin may have a role in the treatment of Candida infections refractory or intolerant to other antifungals (Table 1).

TABLE 1

TABLE 1

Section Description

This section in IDCP represents a summary of information about newly approved drugs for infectious disease practitioners. The product information utilizes a standard format, which is reprinted from http://www.hopkins-id.edu, with permission.

© 2001 Lippincott Williams & Wilkins, Inc.