Drawing the line between adverse effects and avoidable error

Medications that are robustly researched in the course of securing approval from the Food and Drug Administration (FDA) or other foreign governing bodies have established a reasonable scope of safety and efficacy. The clinical benefit of medications is rooted in each one’s pharmacologic and pharmacokinetic properties. Yet, these same properties may serve as predicates for adverse effects and toxicity.

Some side effects are predictable extensions of a drug’s pharmacologic effect, such as obtundation from opioids; others are idiosyncratic reactions, such as hives or blood dyscrasias. Extremes of age, organ dysfunction, concomitant medications and hepatic enzyme polymorphisms are also a few factors that can alter an otherwise predictable response to a medication, leading to unwanted clinical failure or toxicity.

In today’s pharmaceutical research environment, most studies evaluating new drugs targeted for FDA approval involve “clean” subjects. Characteristics of such subjects may include patients with an age range excluding extremes (e.g. 18-65 years); patients with limited co-morbidities, excepting those that might commonly coincide with the condition being treated; and patients with normal to mildly impaired renal or hepatic function. This “clean population” approach reduces the risk of medically complex patients becoming statistical outliers that impede the robustness of the study outcomes.

Once a drug secures FDA approval, however, there are generally no restrictions on providers to prescribe the drug explicitly according to study criteria or even FDA approved labeling. As newly approved drugs enter a prescriber’s pharmacopeia, the patients selected for said medication likely begin to lose their resemblance to the “clean” subjects involved in the original research trials. As the use of a new drug in a more medically complex general population grows, the limits of predictable clinical outcomes become stretched. In unfortunate situations, patient specific factors, pharmacologic principles and/or idiosyncratic reactions intertwine, resulting in an exaggerated clinical response, often a serious adverse effect.

Case example: An 85 year old, frail woman with dementia and chronic kidney disease requires anticoagulation treatment for new onset atrial fibrillation. Because of the complexities of INR monitoring with warfarin, a new oral anticoagulant is deemed preferable. Rivaroxaban (Xarelto) is chosen because it doesn’t require clinical monitoring. Unfortunately, the patient experiences a hemorrhagic stroke. Is this patient one of the 3 percent or so of patients who predictably experience a major bleeding event – an adverse effect? Or, did the prescriber fail to meet the standard of care for anticoagulant treatment?

An expert with extensive knowledge in the pharmacologic basis of medication management and experience in various pharmacy practice settings and academics can serve a critical role in determining causality and viability if such a case were brought to litigation.