There is no standard source for identifying the optimal dosing of medications in patients with obesity. This poses a very difficult scenario for clinicians as they treat patients in this challenging population.
Challenges and questions faced by clinicians in dosing of medications in patients with obesity
Greater than 1 billion people worldwide have obesity. Obesity is a problem that affects every region of the globe:
- From the year 2000 to 2020, the U.S. obesity prevalence increased from 30.5% to 42%.
- According to several sources, including the World Health Organization, the countries with highest prevalence of obesity are Pacific Island nations, followed by Middle Eastern countries.
- Within the Middle East, Kuwait (37.9%) and Saudi Arabia (35.4%) are consistently among the countries with the highest obesity prevalence.
- The U.S. generally ranks the highest in obesity prevalence among Western nations for obesity (36.2%), usually between 10th or 12th out of all nations on most lists. Canada (29.4%) and Mexico (28.9%) also rank in the top 30.
- United Kingdom often has the highest prevalence of obesity within Europe (27.8%).
- The lowest prevalence of obesity tends to be found in East, Southeast, and South Asia, including countries like Japan (4.3%) and India (3.9%).
As someone who has experience taking care of critically ill patients with obesity, I know the importance of determining how to adequately dose medications in this population. Through my work with UpToDate® Lexidrug™ (formerly Lexicomp®) and a team of senior editors who are experts in the obesity field, our goal is to provide clinicians with evidence-based medication dosing content while they treat patients with obesity. To date, the Lexidrug Obesity Dosing Field provides enhanced dosing recommendations for more than 160 drug monographs.
A lot of the obesity dosing content in Lexidrug Obesity Dosing Field covers high-risk medications that are commonly used in the clinical arena. Providing this content will help clinicians determine proper dosing of these medications in the patients that they treat. Some of the medication classes for which we provide specific recommendations in patients with obesity include:
- ICU medications
- Antithrombotics
- Anticoagulants
- Antimicrobials
- Sedatives
- Analgesics
- Corticosteroids
- Neuromuscular blocking agents
- Oncology agents
Clinically, obesity may alter a medication’s pharmacokinetics and pharmacodynamics, leading to therapeutic failure or drug toxicity, and these alterations may be dependent on the overall degree of obesity. To complicate the matter, medication dosing considerations for patients with Class I, II, or III obesity can vary based on the patient’s obesity Class. Because of this, some common questions can arise when treating patients with obesity, such as:
- How to optimize antimicrobial dosing for a patient with obesity who is in septic shock or other disease states?
- What dose of fosphenytoin should be used for a patient with Class III obesity who is in status epilepticus?
Obesity and the impact of antimicrobial medication dosing
Clinicians may choose to use piperacillin/tazobactam to treat a patient with obesity who is in septic shock. Without knowledge of pharmacokinetic and pharmacodynamic changes that occur in patients with obesity and the impact on antimicrobial medication dosing, it is more likely for clinicians to administer non-optimized dosing in this population.
To complicate the antimicrobial dosing decision, the specific dosing recommendations may vary for extended infusion method or traditional infusion method and are dependent on the clinical status of the patient.
In life-threatening infections, patients with extreme obesity (e.g., BMI ≥50 kg/m2), or infection site penetration limitations, the recommendation is an extended infusion method using 4.5 g every 6 hours of piperacillin/tazobactam and infusing each dose over 3 hours. This regimen and dosing method is designed to increase drug concentrations early in the course of therapy, when compared to the traditional infusion method, and thereby increase the likelihood of target concentration attainment at the site of infection, which hopefully will positively impact outcomes in this population.
Vancomycin is another very common medication administered to patients with septic shock. For critically ill patients with obesity, the Lexidrug Obesity Dosing Field recommends an initial loading dose of 20 to 35 mg per kilogram using actual body weight with a maximum initial dose of three grams and then provides content on how to determine the maintenance dose. Similar to piperacillin/tazobactam recommendations, the vancomycin recommendations are developed to help clinicians optimize target concentration attainment early in the course of therapy and ultimately improve patient outcomes.
Optimize antiepileptic dosing in patients with obesity
Depending on the medication in question, dosing recommendations for patients with obesity may be based on different dosing weights: actual body weight, adjusted body weight, lean body weight, or possibly ideal body weight. The determination of the correct dosing weight to use is a common question clinicians face when dosing medications in patients with obesity. The Lexidrug Obesity Dosing Field clearly provides that content for the medications that are dosed by weight so clinicians will have that information at their fingertips instead of having to take valuable time searching the literature for an answer.
Going back to the question of how to dose fosphenytoin, an antiepileptic, in a patient with obesity who is in status epilepticus, the specific dosing recommendation is based on the obesity Class the patient may have (e.g., Class I, II, or III). So, in the particular case of a patient with Class III obesity, the recommendation is an initial loading dose of 15 mg PE (phenytoin equivalent) per kilogram of fosphenytoin using actual body weight to ensure adequate concentrations and efficacy. Conversely, for maintenance dosing the recommendation uses ideal body weight to minimize toxicity.
Providing evidence-based dosing recommendations for patients with obesity
November is National Diabetes Month in the U.S. with November 14 serving as World Diabetes Day globally. As Type 2 diabetes can be closely related to weight and diabetes treatment and management can be impacted by obesity, it’s a good time to focus on reviewing options, tools, and strategies for safe dosing adjustments in patients with obesity.
The increasing prevalence of obesity will continue to challenge clinicians when it comes to providing safe and effective medication therapy to this population. Bringing together established experts in the field to help synthesize the latest data and to develop concise dosing recommendations for clinicians will help them more confidently and more quickly deliver appropriate medication dosing in patients with obesity to enhance their overall care.
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To learn more about weight-based dosing and diabetes, download the eBook, “Building patient-provider partnerships for better diabetes care and management.”
