Variations in Pill Appearance of Antiepileptic Drugs and the Risk of Nonadherence

Pharmacists are aware of medication adherence as well as pharmaceutical and clinical outcome issues surrounding generic drugs. Some pharmacists do exercise professional discretion and judgment when refilling medications with a different NDC. Anecdotally, some pharmacists will make every effort to maintain NDC consistency among refills for antiepileptic drugs and other drug classes.

It is known that patients on daily medications for chronic illnesses are aware of changes in pill appearance [1] and Kesselheim et al. have demonstrated a posteriori that such changes are associated with risk of medication impersistence (i.e, interrupted adherence to maintenance therapy) among patients taking antiepileptic drugs [2]. The authors emphasize differences in appearance between brand-name drugs and generic counterparts. However, it is unclear what percentage of discordant cases were due to substitution of 1) brand drug with a generic drug or 2) generic drug to another generic version. If a drug is available as a generic, patients will often be initiated on the generic drug and may never receive the brand drug.

Based on the study methods (e.g., dates of data collection, antiepileptic drugs), I surmise that changes in pill appearance due to the latter scenario was likely dominant but would like to the authors to clarify. This is important from a pharmaceutical industry and regulatory perspective since “trade dress” jurisprudence, a form of exclusivity, is not likely to be claimed by generic drug manufacturers. 

One step towards reducing variation in generic drug appearance and the potential number of color and shape arrays would involve policy changes that standardize the pill appearance among all marketed generic versions. Therefore, for each dose of a brand drug, there could, in theory, be only one color and shape for the corresponding generic drug and dose, regardless of the generic drug manufacturer. It is also important to note the trend towards use of mail order refill services [3] and that such services appear to be associated with better medication adherence.[4] It is unclear whether Kesselheim et al. controlled for this variable among concordant and discordant cases. For the patients who pick-up their refills in a pharmacy, Kesselheim et al. suggest that “At pharmacies, the ability to alert consumers when pill features have changed may require adaptations to information technology systems.”[2] In fact, such systems are already in place. Pharmacies have software that provide an on-screen alert when there is an NDC change upon medication refill. Depending on the software, the alert will generate either an auxiliary label indicating the potential change in pill appearance and/or similar text on the medication guide. If not, pharmacists may attach an auxiliary label (often referred to as the “green sticker) indicating a potential change in pill appearance. Even in the absence of such systems, pharmacists and pharmacy technicians may use a “show and tell” approach when dispensing refills. This allows the patient an opportunity to visually detect if pill appearance has changed and to seek clarification. However, caregivers may pick-up the refilled medication; anecdotally, in such situations, the new information may not reach the patient. 

I also believe there is variability in consistency of new information being communicated to patients and agree with Kesselheim et al. that “pharmacists might take greater care to alert patients when changes in suppliers lead to new pill characteristics.”[2]

Communication of new information is a team effort and since the act of alerting patients of changes in pill appearance is non-discretionary, pharmacists should remind pharmacy technicians, clerks and pharmacy cashiers to also verbally inform patients of potential changes in pill appearance. 

References

1. Toverud EL, Røise AK, Hogstad G, Wabø I. Norwegian patients on generic antihypertensive drugs: a qualitative study of their own experiences. Eur J Clin Pharmacol. 2011;67(1):33-38.

2. Kesselheim AS, Misono AS, Shrank WH, et al. Variations in pill appearance of antiepileptic drugs and risk of non-adherence. JAMA Intern Med. 2013;173(3):202-208.

3. http://www.nytimes.com/2011/03/04/business/04drug.html?_r=04. Sharma KP, Taylor TN. Pharmacy effect on adherence to antidiabetic medications. Med Care. 2012;50(8):685-691.