Pharmacists Should Consider Pharmacokinetics
Interchangeability is not a given, as patients may experience different reactions when switching to a substitute.
Although generic drugs can be interchangeable with brand name medications and equally therapeutic, some patients may experience clinical discomfort or new adverse effects when switching to a generic option.
This discomfort is caused by pharmacokinetic variability of the active substance, according to an article published in the June edition of Clinical Pharmacokinetics, but does not necessarily warrant a change in the regulatory approach to evaluating bioequivalencies of generic drugs.1
“A demonstration of bioequivalence is the cornerstone of generic drug approval,” the authors wrote.
Bioequivalency is defined as 2 pharmaceutically comparable drug products with statistical proof of bioavailability.1
Despite strict requirements to demonstrate bioequivalency, the authors noted that several aspects of the regulatory approach have been questioned.
Many experts have pointed out that bioequivalence studies are typically conducted with healthy participants rather than the intended patient population, and investigators have questioned whether these data can be accurately extrapolated to patients. Absolute exposure for drugs may be different between patients and healthy participants.1
Others have pointed out that this difference is related to the active substance and is similarly influenced by patient comorbidities for both branded and generic drugs.1
One reason to conduct studies with healthy patients is that they generally have fewer comorbidities, and investigators expect to observe less variability of exposure unrelated to the differences between the drug products, according to the authors.1
Still, the authors concluded that while it may not be necessary, it can be helpful to empirically test comparable relative exposure in both patients and healthy participants.
They pointed out that in a recent comparative bioavailability study conducted with kidney and liver transplant patients, investigators found similar tacrolimus exposure for both brand name and generic drugs.1
“These findings support the current approval pathway for generic drugs and the notion that bioequivalent drugs are expected to be therapeutically equivalent,” the authors wrote.
Still, the authors questioned why adverse effects and clinical discomfort are so common, despite multiple studies demonstrating bioequivalency.
“In our opinion, within-subject pharmacokinetic variability is the most important factor in this debate,” they wrote.1
The authors cited work by Yu et al, which found that people often have an individual exposure ratio outside the acceptance criteria for bioequivalency.
They noted, however, that the same findings can occur with 2 repeated administrations of the same brand name or generic drug, reflecting the daily clinical challenges of treating a patient rather than a failure of regulatory systems.1
Considering the pharmacokinetics, therefore, is essential for pharmacists when looking to exchange a branded drug for a generic option, the authors noted.
Pharmacists should consider designing patient-specific dosage regimens based on both pharmacokinetic and pharmacologic characteristics of the drug, according to a statement from the American Society of Health-System Pharmacists (ASHP).
They also should communicate closely with physicians and other clinical practitioners, monitor pharmacologic responses, and schedule tests of drug concentrations, according to the ASHP.2
- Glerum PJ, Neef C, Burger DM, Yu Y, Maliepaard M. Pharmacokinetics and generic drug switching: a regulator’s view. Clin Pharmacokinet. 2020;59(9):1065-1069. doi:10.1007/s40262-020-00909-8.
- ASHP statement on the pharmacist’s role in clinical pharmacokinetic monitoring. American Society of Health-System Pharmacists. Updated 1998. Accessed August 14, 2020. https://www.ashp.org/-/media/assets/policy-guidelines/docs/statements/pharmacists-role-clinical-pharmacokinetic-monitoring.ashx.