Drug Dosing in the Obese Adult: An Expert Interview With Jeffrey F. Barletta, PharmD, FCCM

Steven Fox

December 14, 2010

December 14, 2010 — Editor's note: Achieving optimal drug dosing in obese adults can be extremely challenging, given the alterations in their pharmacokinetic profiles. Limited data in this population makes the job even more difficult.

Those challenges, along with strategies for managing them, were the focus of an educational session presented at the American Society of Health-System Pharmacists Midyear Clinical Meeting 2010, held December 5 to 9 in Anaheim, California.

Drug Dosing in the Obese Adults was presented by Jeffrey F. Barletta, PharmD, FCCM, associate professor, Department of Pharmacy Practice, College of Pharmacy at Midwestern University in Glendale, Arizona. Dr. Barletta discussed the topic with Medscape Medical News.

Medscape: What are the overall principles that pharmacists need to keep in mind when formulating dosing for patients who are obese?

Dr. Barletta: It can be difficult to take an evidence-based approach when developing dosing regimens for patients with morbid obesity because of the few drug studies conducted in this population. In light of the limited data, there are a few points for consideration.

The first is the safety profile of the medication. Drugs that are typically considered safe (e.g., beta-lactam antibiotics) can be dosed more aggressively than drugs with a narrow therapeutic index (e.g., anticoagulants).

The second is the clinical scenario. For example, is the patient in an intensive care unit? Are they on a ventilator? One might take a different approach when formulating a narcotic dose for an elderly patient who is not mechanically ventilated than for a young patient who is.

The third consideration that needs to be taken into account is the titration strategy. In some cases, despite what the pharmacokinetic data may reveal, the best approach might be the safest approach — that is, using small doses that can be rapidly repeated and titrated to effect rather than administering 1 large dose, which may increase the likelihood of an adverse drug event. The final consideration is whether or not therapeutic drug monitoring is available.

Medscape: Are there special classes of medications that warrant particular care in terms of dosing for the obese patient? If so, which classes? And why?

Dr. Barletta: The 2 classes I tend to think of are the anticoagulants and antimicrobials. Anticoagulants can be somewhat challenging because of the importance of obtaining a rapid therapeutic effect while minimizing the risk of major bleeding. Thus far, there are few studies that have included large numbers of patients with morbid obesity (body mass index above 40 kg/m2), and most utilize a pharmacodynamic end point instead of clinical outcomes. This has led to some disparity in approach.

Antimicrobials can be even more challenging because of the inability to utilize therapeutic drug monitoring for many agents and the importance of early appropriate therapy, particularly in the critically ill.

Medscape: Are there specific clinical situations in obese patients that sometimes entirely preclude the use of certain pharmaceuticals?

Dr. Barletta: I think when treating infections in the morbidly obese population, there could be a preference for one class of agents over another. This will vary from patient to patient, based on the minimum inhibitory concentration (MIC) of the organism and the clinical scenario. Therefore, an individualized approach must be utilized. Clinicians must determine if the pharmacokinetic variability (encountered with obesity) is substantial enough to affect whether or not pharmacodynamic goals can be obtained.

For example, when organisms have a higher MIC for a specific agent, it might be difficult to reach the pharmacodynamic goal that has been identified for that antimicrobial, even in patients who are not obese. When the kinetic variability associated with obesity is introduced, that goal becomes unobtainable. Clinicians should choose agents (e.g., cephalosporin vs fluoroquinolone vs carbapenem) in which the largest margin for error exists, so that kinetic variability will not affect the ability to reach that pharmacodynamic goal. This will vary from patient to patient.

Medscape: What about special considerations in managing the obese elderly?

Dr. Barletta: Whenever end-organ dysfunction is encountered, which is common in the elderly, this adds to the complexity of designing an appropriate dosing regimen. Clinicians must now account for the pharmacokinetic variability associated with obesity and adjust for various degrees of end-organ dysfunction.

Doses are therefore adjusted upward to a certain degree to account for obesity but then lowered to another degree to account for reduced clearance. If therapeutic drug monitoring is not available, clinical response must be closely monitored to ensure that doses are high enough for good outcomes to be obtained but not toxic, making adverse drug events more prominent. Drugs that have short half-lives — for which small doses can be repeated and titrated to effect — are useful in this scenario.

Medscape: What are the main areas of inquiry — the highest-priority questions — that researchers need to pursue to keep improving care in patients who are obese?

Dr. Barletta: I think the question of which weight to use for weight-based dosing still remains unanswered for many agents. For example, clinicians can calculate markedly different dosing regimens (for a weight-based medication) when using ideal body weight, adjusted body weight, or total body weight. In addition, estimating renal function can be problematic because most formulas include weight as part of the calculation but do not adequately define which weight to use for obesity. Finally, more clinical studies are needed specifically in patients with morbid obesity. Many studies that include obese patients only have a small percentage who are morbidly obese.

Dr. Barletta has disclosed no relevant financial relationships.

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