Dosing of antifungal agents in obese people

ABSTRACT

Obesity is a worldwide epidemic associated with multiple comorbidities that increase the risk of hospitalization. Very little pharmacokinetic data are available for antifungal agents in obesity, as this population is often excluded from drug development studies and these agents are less commonly used than other antimicrobials. Systemic antifungal therapy for invasive candidiasis continues to have a high failure rate, and dose optimization in obesity provides an opportunity for improvement. Based on currently available data, some antifungals should be dosed based on total body weight (i.e. fluconazole), while others should not be adjusted for increased body weight (i.e. posaconazole). More studies are needed to determine if and when dosing changes are needed for many of the antifungal agents. Therefore, drug therapy regimens should be individually evaluated for dose optimization due to body weight.

KEYWORDS:

• Antifungal
• obesity
• weight
• pharmacokinetics
• effectiveness
• safety
• azole
• polyene
• echinocandin
• antimetabolite

Acknowledgments

The authors would like to thank Farbod Dehmami and Victoria Felder for their editorial assistance with the manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issue

• Obesity is a global pandemic and is common in hospitalized patients.

• Fluconazole should be dosed based on TBW.

• Micafungin should be dosed using the formula Dose (mg) = patient weight (kg) + 42.

• No dosing alterations are recommended for posaconazole, amphotericin B formulations, or anidulafungin at this time.

• Data are needed to support dosing regimens for itraconazole and flucytosine in obese people.

• Pharmacokinetic and outcome data with obese patients, especially patients weighing >120 kg, are needed to help ensure the provision of dosing regimens that are safe and effective in obese persons.