Bibliographic Info
GuidelineRapid advice : diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children
Year of Publication2011
Issuing InstitutionWorld Health Organization
Recommendation
Status
Maintained
Recommended in favor
Conditional
Certainty of evidence
Low
In HIV-infected adults receiving amphotericin B–containing regimens for treatment of cryptococcal disease, a minimum package of toxicity prevention, monitoring and management is recommended to minimize the serious amphotericin B–related toxicities of hypokalaemia and nephrotoxicity
Notes and Remarks
- 1)In developing these recommendations, the Guideline Development Group placed a high priority on the avoidance of the serious and potentially life-threatening amphotericin B-related toxicities of hypokalaemia and nephrotoxicity, balanced against the need for a simplified approach to prevention, monitoring and management of drug toxicities, and and approach that is feasible in RLS.
- 2)The Guideline Development Group reviewed evidence on the significant risk of toxicity with amphotericin B-based regimens. Rates of hypokalaemia ranged from 11% to 33% in five RCTs and rates of nephrotoxicity from 1.3% to 14.8% in three RCTS. A protocol for twice-weekly monitoring of potassium and creatinine, particularly in the second week, and a haemoglobin weekly was based on evidence from all trials and observational studies that the highest incidence of toxicities occurred in the second week of therapy. The incidence of liver dysfunction with fluconazole remains low, therefore, routine monitoring of liver function was not recommended.
- 3)A simplified protocol for pre-hydration and electrolyte replacement prior to each amphotericin B infusion is a core recommendation, based on evidence from a pooled analysis of data from two RCTs and two observational studies that the incidence of these toxicities can be substantially reduced using this approach. In two RCTs of patients receiving amphotericin B for leishmaniasis, there was significant reduction in either the development of hypokalaemia or nephrotoxicity following pre-hydration with intravenous normal saline. In a further cohort of patients receiving pre-hydration with normal saline and potassium replacement prior to amphotericin B, 79% received a complete treatment course without major adverse events, and fewer than 8% or 20% respectively developed a significant rise in creatinine or had severe hypokalaemia. Finally, in a small sub-analysis of data on patients within an ongoing RCT of CM, there was a marked reduction in the incidence of grade 3 or higher hypokalaemia after universal electrolyte supplementation was introduced in addition to pre-hydration.
Also Featured In
This recommendation also appears in the following guidelines:
Guideline
Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
Year2016
InstitutionWHO