Based on their findings that patients are more likely to stop taking antiepileptic drugs when pills change color upon refill, researchers argue that the FDA should require generic pills to mimic the appearance of their brand-name equivalents.
Patients taking a generic medication whose color differs from that of the brand-name equivalent or from other generic versions appear to be more likely to stop taking the medication, according to the results of a study
published online on December 31, 2012, in JAMA Internal Medicine
, formerly known as Archives of Internal Medicine
Although the FDA requires generic medications to be bioequivalent to their brand-name counterparts, it does not require generics to mimic the brand-name version’s color and shape. In some cases, brand-name manufacturers claim an exclusive right to their medications’ physical characteristics, requiring that generics have a different appearance. As a result, patients who switch from brand-name to generic or between generic versions may become confused and fail to take their medication as prescribed.
Since reduced medication adherence can have serious consequences, a team of researchers from Harvard University set out to determine whether patients who switched from a version of an antiepileptic drug (AED) to another with a different appearance demonstrated reduced rates of persistence. The researchers drew on data from health insurance databases covering 14 states between 2001 and 2006 to look at patients who started taking an AED that was available in pill form and had at least 1 brand-name and 1 generic form available during the study period.
The study included 11,472 nonpersistent case patients, who failed to fill a prescription for an AED within 5 days of running out of their previous prescription, and 50,050 matched controls, who refilled their prescriptions without delay. The AEDs included in the study were carbamazepine, carbamazepine extended-release, ethosuximide, lamotrigine, phenytoin sodium, valproic acid, and zonisamide. In all, the medications were dispensed in 37 different colors and 4 different shapes. Among the different AEDs, color variation ranged from none (all valproic acid pills were orange) to extensive (ethosuximide came in 19 different color possibilities).
The results showed that color discordance preceded 1.20% of nonpersistent cases compared with 0.97% of controls (adjusted odds ratio of 1.27). Shape discordance preceded 0.16% of nonpersistent cases compared with 0.11% of controls (adjusted odds ratio of 1.47, although this was not statistically significant). Among participants with a seizure disorder diagnosis (approximately one-fifth of cases and controls), the risk of nonpersistence after a change in pill color was also significantly elevated (adjusted odds ratio of 1.53). The researchers note that neither shortening the definition of nonpersistence to a lapse of 3 days in filling the prescription nor lengthening it to 10 days substantially changed the results.
The researchers note that possible explanations for increased nonpersistence with pill color changes include patient confusion, especially among those taking multiple medications, and that some patients may associate the appearance of a medication with its efficacy and therefore consider a bioequivalent pill with a different appearance ineffective. (The latter phenomenon is termed the nocebo effect.) The researchers suggest that their findings may help explain why some have argued that generic AEDs are not as effective as their brand-name equivalents; since patients may be less likely to be persistent when using generics, they may appear to be less effective.
Based on the results, pharmacists may want to warn patients of potential changes in pill appearance when they are switching from a brand-name to a generic or among generic versions of the same medication. In addition, the researchers note that their results should prompt the FDA to consider standardizing the appearance of a given medication. At the very least, they argue, the findings should lead to the elimination of brand-name manufacturers’ exclusive right to the appearance of their medications, as such protections are only allowed for non-functional attributes.