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caspofungin (Cancidas)

Tradename: Cancidas. Indications: 1) HIV antifungal agent a) treatment of invasive aspergillosis b) 2nd line agent for patients who do NOT respond to or cannot tolerate amphotericin B or itraconazole 2) treatment of infections due to Candida a) Candida glabrata b) esophageal candidiasis c) oropharyngeal candidiasis [3] d) candidemia 3) empiric treatment of febrile neutropenia [3] Contraindications: - cryptococcosis (lack of antimicrobial activity) Dosage: 1) 70 mg IV infused over 1 hour, then 50 mg IV QD 2) 70 mg/day if coadministered with rifampin 3) by infusion only (infuse slowly, over 1 hour) 4) do NOT coadminister with other medications No dosage adjustment with renal failure. Hepatic failure (Child-Pugh score of 7-9): - decrease dose to 35 mg/day Pharmacokinetics: 1) 97% bound to albumin 2) hepatically cleared via hydrolysis & N-acetylation 3) spontaneous degradation 4) elimination a) 50% in urine (1-9% unchanged; 40% as metabolites) b) 35% in feces as metabolites 5) poor penetration into the CNS [2] Antimicrobial activity: 1) Aspergillus 2) Candida Adverse effects: 1) common (> 10%) a) headache (11%) b) fever (3-26%) c) decreased hemoglobin (3-12%) d) increased LFTs (alkaline phosphatase, transaminases) 3-13% e) infusion site reactions/phlebitis (2-16%) 2) not common (1-10%) a) cardiovascular: - flushing, hypertension, hypotension, tachycardia b) central nervous system: dizziness, pain, insomnia c) gastrointestinal: - nausea/vomiting, abdominal pain, diarrhea, anorexia d) hepatic: increased bilirubin e) renal: - nephrotoxicity (8%), proteinuria (5%), hematuria, pyruria, increased serum creatinine f) metabolic: hypokalemia (10%) g) hematologic: - eosinophilia, neutropenia, leukocytosis, anemia, thrombocytopenia h) neuromuscular: myalgia, paresthesia, tremor i) skin j) other - flu-like syndrome, diaphoresis 3) uncommon (< 1% - ARDS, anaphylaxis, hepatic dysfunction, pulmonary edema, renal insufficiency Drug interactions: 1) coadministration with cyclosporine increases liver toxicity 2) rifampin may diminish caspofungin concentrations 3) caspofungin may diminish tacrolimus concentrations Mechanism of action: 1) echinocandin 2) inhibits formation of fungal cell walls 3) inhibits synthesis of beta(1,3)-D-glucan* 4) highest activity in regions of active growth * mammalian cells do not require beta(1,3)-D-glucan Notes: Manufacturer: Merck

Interactions

drug interactions

General

echinocandin

Properties

MISC-INFO: elimination route LIVER 1/2life 9-11 HOURS 40-50 HOURS protein-binding 97% elimination by hemodialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 8(3):15 2001 Lexi-Comp Online 2004
  2. Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
  3. Deprecated Reference