Bibliographic Info
Recommendation
Recommended in favor
Strong
Certainty of evidence
Moderate
(Treating people with cryptococcal meningitis) If no amphotericin formulation is available: 14 days of fluconazole (1200 mg daily, 12 mg/kg per day for children and adolescents) and flucytosine (100 mg/kg per day, divided into four doses per day)
Notes and Remarks
fluconazole + flucytosine is the only recommended oral combination regimen and has been associated with lower mortality compared with amphotericin B deoxycholate + fluconazole. Drug–drug interactions Drug–drug interactions in the context of concurrent use of amphotericin, flucytosine and fluconazole alongside ART regimens have not been well documented (135). However, individuals receiving tenofovir disoproxil fumarate (TDF)–based regimens who are receiving amphotericin or recently received amphotericin B preparations should be closely monitored for nephrotoxicity. Liposomal preparations of amphotericin B are considered to be safer (133) than deoxycholate but would still require close follow-up. The dose of tenofovir disoproxil fumarate should be adjusted for renal function. Flucytosine may slightly alter levels of TDF in the blood through reduced renal clearance, but this remains a theoretical risk. Haematological parameters should be monitored, and the dose of tenofovir disoproxil fumarate should be adjusted in individuals with reduced renal function who are also receiving amphotericin (136). Fluconazole induces cytochrome (CYP)3A4 and P-glycoprotein (137). No dose adjustment of ART is required.
Also Featured In
This recommendation also appears in the following guidelines:
Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV.