Table 8.

Conceptual framework for dosing medications in obese patients¹

Step 1

Evaluate the clinical investigations involving the medication to determine the degree of obesity in the patients under study and the weight descriptor used for dosing, which is usually actual body weight (ABW) in studies leading to medication approval. Determine if the patient under consideration appears to fit the profile of the patients in the study; be particularly cautious if the patient is extremely obese. If the patient appears to fit the profile of the patients in the studies, use the weight descriptor. If not, proceed to Step 2

↓

Step 2

If the patient does not fit the profile of the patients in the clinical investigations, search the literature for pharmacokinetic studies involving the medication in obese patients. Assess whether the pharmacokinetic parameters of the medication appear to increase proportionately with increasing weight suggesting that use of ABW may be appropriate. If the patient appears to fit the profile of the patients in the studies, consider using the weight descriptor and proceed to Step 5. If not, proceed to Step 3

↓

Step 3

If the patient does not fit the profile of the patients in the clinical investigations and if no pharmacokinetic studies involving the specific medication in obese patients are available, evaluate the literature for dosing studies in obese patients with medications that have similar physicochemical and pharmacokinetic parameters (e.g., medications in the same class). If the patient appears to fit the profile of the patients in the studies, consider using the weight descriptor and proceed to Step 5. If not, proceed to Step 4

↓

Step 4

If no relevant studies can be found, and particularly if the patient is extremely obese, assess whether an alternative medication (where more is known about dosing in obese patients) might be appropriate. If there is no equivalent or better medication option available, proceed to Step 5

↓

Step 5

Assess the benefits and risks of using ABW for dosing using step 5a for weight-based dosing or 5b for non-weight based dosing

Step 5a

If weight-based dosing (e.g., mg/kg) is being used, assess whether the potential benefits of using ABW (e.g., need to reach therapeutic range quickly) are likely to exceed the potential risks of over-dosing. If the patient under consideration is substantially heavier than the patients in the investigations or if no studies are available, assess whether a lean body weight or adjusted body weight equation might be preferable, especially in medications with a narrow therapeutic range and small (e.g., < 0.2 L/kg) to moderate (e.g., 0.2 to 1 L/kg) volumes of distribution that are cleared primarily by glomerular filtration

Step 5b

If non-weight-based dosing (e.g., mg/dose) is being used, assess whether the potential benefits of using a larger dose are likely to exceed the potential risks of over-dosing if the patient under consideration is substantially heavier than the patients who were enrolled in the clinical investigations involving the medication, and if the medication has a narrow therapeutic range and a moderate (0.2 to 1 L/kg) to large (> 1 L/kg) volume of distribution

¹Should always take into account potential co-morbidity confounders such as renal or liver dysfunction when determining dosing regimens. Reprinted with permission from Erstad[57].