More consideration needs to be given to a patient’s body composition when medicine doses are being calculated, experts believe
Estimating the optimal dose for obese patients is difficult and, in many cases, ill defined, say clinical pharmacists in a recent article.
Writing in Australian Prescriber, Brisbane-based hospital pharmacists Michael Barras and Amy Legg said that “basing maintenance doses on total body weight is unlikely to result in a comparable drug response across different body sizes and generally increases the risk of adverse events”.
Instead they say that “individualised dosing based on the patient’s lean body weight is recommended, with accompanying therapeutic drug monitoring and monitoring of the patient’s clinical response”.
Given the increasing rates of obesity – around 65% of Australian adults are classed as obese or overwieght – there is little evidence and guidance on how to ascertain the optimal medicines dosage for these people, they say.
“Drug doses are usually calculated using a patient’s total body weight. This is often inappropriate for obese patients. Significant variations in pharmacokinetic and pharmacodynamic responses can occur between patients due to weight, age, genetics, concurrent diseases and other factors,” the authors said.
“Ideally, the ‘one dose fits all’ paradigm should be replaced by individualised dosing methods”.
Drugs that commonly require dose adjustment in obese patients include low-molecular-weight heparins, aminoglycoside antibiotics, some anaesthetics, monoclonal antibodies and chemotherapeutics.
An example of the dilemma of weight-based dosing the authors mentioned was enoxaparin, for which the licensed dose for treatment of venous thromboembolism is based on total body weight (mg/kg).
“Many clinicians recognise that this results in high doses in obesity and increases the risk of toxicity, so they reduce or cap the dose (often at 100 mg) in patients over 100 kg. This may result in sub-therapeutic anti-Xa concentrations, particularly in morbid obesity, as clearance increases with body size”.
“A dose based on lean body weight is warranted in this case and a dose of 1.5 mg/kg (lean body weight) has been proposed. The prophylactic dose is usually 20–40 mg daily. As clearance increases with body size, the dose should be increased in morbid obesity and suggested doses include 30–40 mg twice daily”.
The authors said that more clinical trials that stratify doses across a range of body weights were needed to improve drug-dosing knowledge.
“In the meantime, we need to rely on scientific principles to dose many drugs in the obese”.