Cryptococcosis induction therapy

For cryptococcosis induction therapy in adults and children requiring 3-phase antifungal therapy, as a 2-drug regimen, useChang 2021:

amphotericin B liposomal (adult and child) 3 to 4 mg/kg intravenously, daily12. See advice on duration of therapyamphotericin b liposomalamphotericin B liposomalamphotericin B liposomal

PLUS

flucytosine (adult and child) 25 mg/kg orally, 6-hourly. For dosage adjustment in adults with kidney impairment, see flucytosine dosage adjustment. Monitor plasma concentration and full blood count (see Monitoring flucytosine)34. See advice on duration of therapy. flucytosine flucytosine flucytosine

For patients weighing more than 120 kg, amphotericin and flucytosine dosing is uncertain – seek expert advice.

Alternative drugs and regimens have been used for induction therapy of cryptococcosis but due to increased risk of toxicity, inferiority, or lack of experience outside of resource limited settings, are usually not preferred. Such regimens includeChang 2024:

  • alternative amphotericin formulations (ie amphotericin B deoxycholate [0.8 to 1.0 mg/kg/day] or amphotericin B lipid complex)56
  • amphotericin-based therapy without flucytosine
  • high-dose fluconazole (800 to 1200 mg daily) with or without flucytosine
  • a single high-dose of amphotericin B liposomal (10 mg/kg) with 14 days of oral flucytosine and high dose fluconazole7Jarvis 2022.
1 Lower doses of amphotericin B liposomal (eg 1 to 2 mg/kg) may be as effective as standard doses (ie 3 to 4 mg/kg) – seek expert advice. Hughes CM, Lennon D, Davis JS. CRyptOcoccosis in Newcastle and the hUnTer (CRONUT) - An epidemiological study. Infect Dis Health 2020;25(1):34-42. [URL].Return
2 Amphotericin B liposomal is associated with significant toxicity; see Practical information on using polyenes.Return
3 Oral flucytosine is not registered for use in Australia but is available via the Special Access Scheme.Return
4 If oral flucytosine is not tolerated, consider administration via a nasogastric tube; consult a hospital pharmacy service or medicines information service for preparation instructions. If oral or nasogastric administration is not possible, seek expert advice.Return
5 Amphotericin B deoxycholate costs less than amphotericin B liposomal but is more toxic.Return
6 Amphotericin B lipid complex and amphotericin B desoxycholate are not registered for use in Australia but are available via the Special Access Scheme.Return
7 Jarvis JN, Lawrence DS, Meya DB, Kagimu E, Kasibante J, Mpoza E, et al. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. N Engl J Med 2022;386(12):1109-20 [URL].Return