Bibliographic Info
Recommendation
Recommended in favor
Strong
Certainty of evidence
Moderate
(Treating people with cryptococcal meningitis) If liposomal amphotericin B and flucytosine are not available: 14 days of amphotericin B deoxycholate (1 mg/kg per day) and fluconazole (1200 mg daily, 12 mg/kg per day for children and adolescents up to a maximum of 800 mg daily).
Notes and Remarks
flucytosine-containing regimens are superior, and steps should be taken to ensure access to this drug. Preventing, monitoring and managing amphotericin B deoxycholate toxicity Infusion-related toxicity and side-effects from amphotericin B therapy are barriers to optimal induction treatment, especially in low- and middleincome countries. Safe administration of amphotericin B should be given priority and may require referral to a centre with access to the recommended package of preventing, monitoring and managing toxicity. Liposomal amphotericin B has fewer risks of drug toxicity than amphotericin B deoxycholate and requires a less intensive package for preventing, monitoring and managing toxicity. The recommended package of preventing, monitoring and managing toxicity should be provided to minimize the serious types of amphotericin B–related toxicity when using amphotericin B deoxycholate–based regimens, especially hypokalaemia, nephrotoxicity and anaemia. A single 10 mg/kg dose of liposomal amphotericin B and the seven-day amphotericin B deoxycholate regimen are better tolerated than a 14-day amphotericin deoxycholate regimen, but these regimens still require careful monitoring. Adverse events associated with amphotericin B deoxycholate include hypokalaemia, nephrotoxicity and anaemia (136–138). A protocol for monitoring potassium, magnesium (if available) and creatinine and weekly haemoglobin monitoring is advised, together with a simplified protocol for prehydration and electrolyte replacement before each amphotericin B infusion. If clients are also receiving a dolutegravir-based regimen, time-separated supplementation of magnesium is necessary to avoid affecting the absorption of dolutegravir (62). Dose adjustment is needed for people with significant renal impairment. Liposomal, deoxycholate and lipid complex amphotericin B formulations are not interchangeable. Various formulations of amphotericin B are available commercially, including liposomal, deoxycholate and lipid complex formulations. These formulations are not interchangeable. For the indication of cryptococcal meningitis, only amphotericin B deoxycholate and liposomal amphotericin B have been recommended. In health-care settings in which both amphotericin B deoxycholate and liposomal amphotericin B are available, healthcare providers must be cautious to avoid mixing up these products since the doses are different and significant adverse events have been reported when the deoxycholate formulation was given at a higher dose than recommended. 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.