NEODOSE

INDICATIONS

• Aspergillus or Candida Infection: Treatment of patients with refractory Candidemia, intra-abdominal abscesses, peritonitis and pleural space infections, and those patients intolerant of amphotericin B. Treatment of invasive Aspergillosis in patients who are refractory to or intolerant of other therapies. There are case reports, but not controlled clinical trials, treating endocarditis, osteomyelitis, and meningitis due to Candida.
• Neonatal Candidiasis, Including CNS Infection:
  • Invasive candidiasis, candidemia, or very low-birth weight infants with asymptomatic candiduria
    • Amphotericin B deoxycholate is recommended.
    • Fluconazole IV or oral is an alternative for those who have not been receiving prophylaxis with fluconazole.
    • Lipid formulation amphotericin B agent is an alternative; however, use with caution, especially in the presence of urinary tract involvement.
    • Echinocandins (caspofungin, anidulafungin, or micafungin) should be limited to salvage therapy or scenarios of resistance or toxicity to amphotericin B deoxycholate or fluconazole.
  • Central nervous system infections.
    • Amphotericin B deoxycholate is recommended.
    • Liposomal amphotericin B agent is an alternative.
    • Salvage therapy with flucytosine may be added in those patients who have not responded to initial therapy.
    • Fluconazole may be used as step-down therapy for fluconazole-susceptible isolates in those patients who respond to initial therapy.
  • Neonatal intensive care unit (with greater than 10% rate of invasive candidiasis)
    • Prophylaxis with IV or oral fluconazole for 6 weeks is recommended for neonates with birth weights of less than 1000 g
    • Prophylaxis with oral nystatin is an alternative in neonates with birth weights of less than 1500 g when fluconazole is unavailable or fluconazole resistance is present

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  Comparison to Amphotericin B: There was no difference in clinical response between echinocandins and amphotericin B (OR 1.38; 95% CI, 0.68 to 2.8) for the treatment of suspected or confirmed invasive candidiasis in a meta-analysis (n=5; 354 neonates and children). Antifungals included were micafungin, caspofungin, amphotericin B deoxycholate, and liposomal amphotericin B. Subanalysis demonstrated no difference in other comparisons including mycological response, mortality, recurrence of candida infection, type of echinocandin, different risk groups (high-risk, low-risk, or neutropenic groups), and type of use (targeted or empirical). Discontinuation due to adverse effects were higher with amphotericin B than the echinocandins (OR 0.3; 95% CI, 0.12 to 0.76).

FDA APPROVED INDICATION

The following indications are FDA approved for pediatric patients 3 months and older.

• Empirical therapy for presumed fungal infections in febrile, neutropenic patients.
• Treatment of candidemia and the following Candida infections: intraabdominal abscesses, peritonitis and pleural space infections.
• Treatment of esophageal candidiasis.
• Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies.

PRECAUTIONS

• Concomitant Use:
  • Increased risk of hepatotoxicity when used with cyclosporine.
• Dermatologic:
  • Stevens-Johnson syndrome and toxic epiderma necrolysis, sometimes fatal, have been reported; discontinue at first sign or symptom.
• Hepatic:
  • Hepatic abnormalities, including abnormal liver function tests and hepatic failure, have been reported; monitoring recommended.
  • Dose adjustment may be required for hepatic impairment.
• Immunologic:
  • Anaphylaxis and other hypersensitivity reactions have been reported; discontinue use if occurs.
  • Histamine-mediated adverse reactions (eg, rash, facial swelling, angioedema, pruritus, sensation of warmth, bronchospasm) have been reported; discontinuation may be necessary.

ADVERSE EFFECTS

Adverse effects reported in neonates (small number of patients): thrombophlebitis, hypercalcemia, hypokalemia, elevated liver enzymes, and isolated direct hyperbilirubinemia. In pediatric studies, the primary adverse effects were fever, hypokalemia, diarrhea, increased liver enzymes, rash, hypotension and chills.

ADMINISTRATION

Administer by slow IV infusion over approximately 1 hour at a concentration not to exceed 0.5 mg / mL.The recommended concentration is 0.5 mg / mL. Do not dilute in dextrose – containing solutions.

MONITORING

Assess IV site for signs of irritation. Periodic measurement of serum potassium, calcium, and hepatic transaminases. For candidemia, monitor blood cultures daily or every other day until Candida is cleared.