Medication dosing in patients with obesity
Clear guidance can be hard to come by for MEDICATION DOSING IN PATIENTS WITH OBESITY (body mass index [BMI] of 30 or higher). Less than 15% of package inserts for acute care medications give adequate dosing information for these patients. And even fewer labels provide guidance for severe obesity (BMI of 40 or more). Plus there isn’t a reliable rule of thumb based on any single drug property, such as lipophilicity or volume of distribution. Work with colleagues to standardize dosing in obesity and address these key points.
SPECIFY WHICH WEIGHT TO USE ㅡ For example, consider ideal weight for IVIG, there’s no proof that using actual weight improves outcomes. And generally use adjusted weight for daptomycin, it might reduce toxicity, and efficacy seems similar to actual-weight dosing. But allow exceptions. For instance, think about using actual weight to dose daptomycin for endocarditis due to vancomycin-resistant enterococcus. Monitor creatine phosphokinase for daptomycin toxicity.
ASSESS DOSE CAPS ㅡ For example, if loading vancomycin for serious infections, use a lower 20 to 25 mg/kg dose instead of up to 35 mg/kg. And ADD a cap of up to 3000 mg to avoid overshooting goal levels. On the other hand, don’t cap the dose with most chemotherapy to ensure therapeutic dosing.
EVALUATE MEDICATIONS WITH FLAT DOSING ㅡ For instance, stick with standard meropenem doses in obesity, BUT consider extended infusions over 3 to 4 hours to optimize pharmacodynamics.
FOLLOW STANDARD DOSING for direct oral anticoagulants (DOACs) in patients with a BMI of 30 to 40. For a BMI over 40, generally use warfarin first. If a DOAC is needed, consider apixaban (Eliquis) or rivaroxaban (Xarelto) based on limited evidence.
Provide guidance on CALCULATING creatinine clearance. Use the weight indicated in labeling, such as actual weight with dofetilide. There’s no consensus for the “best” approach if labeling doesn’t specify. Lean toward using adjusted weight.
REFERENCES
Eastman C, Erstad BL. Availability of information for dosing commonly used medications in special ICU populations. Am J Health Syst Pharm. 2020 Mar 24;77(7):529-534. Available at: https://pubmed.ncbi.nlm.nih.gov/32207817
Smit C, De Hoogd S, Brüggemann RJM, Knibbe CAJ. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol. 2018 Mar;14(3):275-285. Available at: https://pubmed.ncbi.nlm.nih.gov/29431542
Stump SE, Schepers AJ, Jones AR, Alexander MD, Auten JJ. Comparison of Weight-Based Dosing Strategies for Intravenous Immunoglobulin in Patients with Hematologic Malignancies. Pharmacotherapy. 2017 Dec;37(12):1530-1536. Available at: https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2047
Fox, A.N., Smith, W.J., Kupiec, K.E., Harding, S.J., Resman-Targoff, B.H., Neely, S.B., White, B.P. and Owens, R.E. (2019). Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight. Therapeutic Advances in Infectious Disease, 6, p.204993611882023. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354309
Sebaaly J, Kelley D. Direct Oral Anticoagulants in Obesity: An Updated Literature Review. Ann Pharmacother. 2020 Nov;54(11):1144-1158. Available at: https://journals.sagepub.com/doi/10.1177/1060028020923584?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&