caspofungin (Cancidas)

Introduction

Tradename: Cancidas.

Indications

• HIV antifungal agent
  • treatment of invasive aspergillosis
  • 2nd line agent for patients who do NOT respond to or cannot tolerate amphotericin B or itraconazole
• treatment of infections due to Candida
  • Candida glabrata
  • esophageal candidiasis
  • oropharyngeal candidiasis
  • candidemia
• empiric treatment of febrile neutropenia

Contraindications

• cryptococcosis (lack of antimicrobial activity)

pregnancy category = c

safety in lactation = ?

Dosage

• 70 mg IV infused over 1 hour, then 50 mg IV QD
• 70 mg/day if coadministered with rifampin
• by infusion only (infuse slowly, over 1 hour)
• 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

• 97% bound to albumin
• hepatically cleared via hydrolysis & N-acetylation
• spontaneous degradation
• elimination
  • 50% in urine (1-9% unchanged; 40% as metabolites)
  • 35% in feces as metabolites
• poor penetration into the CNS

elimination via liver

1/2life = 9-11 hours distribution

1/2life = 40-50 hours terminal

protein binding = 97 %

elimination by hemodialysis = -

Antimicrobial activity

• Aspergillus
• Candida

Adverse effects

• common (> 10%)
  • headache (11%)
  • fever (3-26%)
  • decreased hemoglobin (3-12%)
  • increased LFTs (alkaline phosphatase, transaminases) 3-13%
  • infusion site reactions/phlebitis (2-16%)
• not common (1-10%)
  • cardiovascular:
    • flushing, hypertension, hypotension, tachycardia
  • central nervous system: dizziness, pain, insomnia
  • gastrointestinal:
    • nausea/vomiting, abdominal pain, diarrhea, anorexia
  • hepatic: increased bilirubin
  • renal:
    • nephrotoxicity (8%), proteinuria (5%), hematuria, pyruria, increased serum creatinine
  • metabolic: hypokalemia (10%)
  • hematologic:
    • eosinophilia, neutropenia, leukocytosis, anemia, thrombocytopenia
  • neuromuscular: myalgia, paresthesia, tremor
  • skin
  • other - flu-like syndrome, diaphoresis
• uncommon (< 1%
  • ARDS, anaphylaxis, hepatic dysfunction, pulmonary edema, renal insufficiency

Drug interactions

• coadministration with cyclosporine increases liver toxicity
• rifampin may diminish caspofungin concentrations
• caspofungin may diminish tacrolimus concentrations

• drug interaction(s) of antibiotics with warfarin

Mechanism of action

• echinocandin
• inhibits formation of fungal cell walls
• inhibits synthesis of beta(1,3)-D-glucan*
• highest activity in regions of active growth

* mammalian cells do not require beta(1,3)-D-glucan

Notes

Manufacturer: Merck

More general terms

• echinocandin

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2826718
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3036598
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5311039