Active ingredient: Caspofungin - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antifungals

Dosage Forms

• Powder for solution

Brands / Synonyms

Cancidas; Caspofungin acetate

Indications

For the treatment of esophageal candidiasis and invasive aspergillosis in patients who are refractory to or intolerant of other therapies.

Pharmacology

Caspofungin is an antifungal drug, and belongs to a new class termed the echinocandins. It is used to treat Aspergillus and Candida infection, and works by inhibiting cell wall synthesis. Antifungals in the echinocandin class inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-beta glucan synthase. There is a potential for resistance development to occur, however in vitro resistance development to Caspofungin by Aspergillus species has not been studied.

Mechanism of Action

Caspofungin inhibits the synthesis of b (1,3)-D-glucan, an essential component of the cell wall of Aspergillus species and Candida species. b (1,3)-D-glucan is not present in mammalian cells. The primary target is beta-(1,3)-glucan synthase.

Absorption

92% tissue distribution within 36-48 hours after intravenous infusion

Toxicity

Side effects include rash, swelling, and nausea (rare)

Biotrnasformation / Drug Metabolism

Metabolized slowly by hydrolysis and N-acetylation

Contraindications

CANCIDAS is contraindicated in patients with hypersensitivity to any component of this product.

Drug Interactions

Studies in vitro show that caspofungin acetate is not an inhibitor of any enzyme in the cytochrome P450 (CYP) system. In clinical studies, caspofungin did not induce the CYP3A4 metabolism of other drugs. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes.

Clinical studies in healthy volunteers show that the pharmacokinetics of CANCIDAS are not altered by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus. CANCIDAS has no effect on the pharmacokinetics of itraconazole, amphotericin B, or the active metabolite of mycophenolate.

CANCIDAS reduced the blood AUC_0-12 of tacrolimus (FK-506, PrografÒ³) by approximately 20%, peak blood concentration (C_max) by 16%, and 12-hour blood concentration (C_12hr) by 26% in healthy subjects when tacrolimus (2 doses of 0.1 mg/kg 12 hours apart) was administered on the 10th day of CANCIDAS 70 mg daily, as compared to results from a control period in which tacrolimus was administered alone. For patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended.

In two clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35%. CANCIDAS did not increase the plasma levels of cyclosporine. There were transient increases in liver ALT and AST when CANCIDAS and cyclosporine were co-administered.

A drug-drug interaction study with rifampin in healthy volunteers has shown a 30% decrease in caspofungin trough concentrations. Patients on rifampin should receive 70 mg of CANCIDAS daily. In addition, results from regression analyses of patient pharmacokinetic data suggest that co-administration of other inducers of drug clearance (efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine) with CANCIDAS may result in clinically meaningful reductions in caspofungin concentrations. It is not known which drug clearance mechanism involved in caspofungin disposition may be inducible. When CANCIDAS is co-administered with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, use of a daily dose of 70 mg of CANCIDAS should be considered.