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Description |
Reference |
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Candidiasis: 12mg/kg x1 load, then 6mg/kg q24h (TBW) Doses up to 1200 mg daily have been reported in the
literature for Cryptococcus meningitis - In critically ill, esp with CrCl
> 50, higher doses may be warranted to achieve PK/PD target of fAUC/MIC
> 100, esp if MIC > 2 Candida spp - Consider TDM for severe infections *TBW = Total body weight = Actual body weight |
SHC Healthcare 2020 |
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Population PK models devised in patient populations
with BMI classifications of obese (30–40 kg/m2 ) and morbidly obese (.40
kg/m2 ) suggest that fluconazole should be dosed based on total body weight
(12 mg/kg loading dose, followed by 6 mg/kg/day maintenance) adjusted for
renal function. |
Pea & Lewis. Overview of antifungal dosing in
invasive candidiasis. J Antimicrob
Chemother 2018; 73 Suppl 1: i33–i43 |
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A fluconazole loading dose of 12 mg/kg and
maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher
MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance
dose of 6 mg/kg, according to renal function, is required in critically ill
patients for pathogens with a MIC of 2 mg/liter The results of this study suggest that a higher
fixed fluconazole dose (i.e., 400 mg daily) is required in these patients
when they are infected by less susceptible Candida spp. (MIC of 2 mg/liter).
Our results show that a loading dose of 12 mg/kg followed by a maintenance
dose of 6 or 12 mg/kg/day is required to achieve either the low or high PK/PD
target. Finally, loading doses should be weight based, whereas maintenance
doses should be prescribed according to renal function. |
Alobaid
et al. Effect of Obesity on the Population Pharmacokinetics of Fluconazole in
Critically Ill Patients. Antimicrob
Agents Chemother 60:6550 –6557. doi:10.1128/AAC.01088-16
https://aac.asm.org/content/aac/60/11/6550.full.pdf |
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Larger dose possibly required but data insufficient
for a firm recommendation Case reports suggest larger dose required in
critically ill obese patients. Recent paper suggests that weight based dosing
(12 mg/kg load, then 6 mg/kg/day using total BW) reaches desired PK/PD
targets more reliably than fixed dosing; clinical validation required. |
Sanford apps |
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· Obese patients are less likely to achieve the dose/MIC and AUC/MIC
ratios of fluconazole that have been previously associated with decreased mortality. · Fluconazole should be dosed based on total body weight to achieve
the AUC/MIC ratios that have previously been associated with favorable
responses. · Fluconazole has a favorable adverse effect profile. Doses
of up to 1200 mg/day for two weeks have been described in the literature –
for cryptococcal meningitis U/L HIV positive patients in Malawi as standard
dose of 800 mg daily is less efficacious there – NOT obese population. [https://pubmed.ncbi.nlm.nih.gov/25375145/] |
Payne & Hall. Dosing of
antifungal agents in obese people. Expert Rev Anti Infect Ther. 2016;14(2):257-67 |
Accessed by JCK Ho on 29.11.2020
