Sustained-release Preparations and Medication Errors

Medication safety is an important problem. While many benefits occur as a result of our current pharmacological armamentarium, all too often patients suffer adverse consequences related to the medications they take, and many of these adverse drug events are preventable. In one large study, the incidence of adverse drug events was 6.5 per 100 admissions, and 28% were preventable.¹

However, collecting data about medication errors and adverse drug events has been time-consuming and expensive. One inexpensive source of a large number of medication errors has been pharmacy logs of the errors detected by pharmacists in routine care. However, in most institutions these errors are “thrown away.” Although many general internists may not be familiar with the group's work, Dr. Lesar's group has been the national leader in collecting errors detected by pharmacists. They have used them to learn extremely valuable lessons about medication safety across a variety of domains, including assessment of factors related to prescribing errors, use of medication dosing equations, and antiretroviral therapy.^2–4 Such errors can be viewed as “pearls,” and they should be collected in many more institutions.

In this study, Lesar used errors detected by pharmacists to study the epidemiology of prescribing errors involving medication dosing forms.⁵ Increasingly, medications have been released in sustained-release preparations, which can be taken once daily as opposed to multiple times, and may improve adherence in the outpatient setting. Adherence is an extremely important problem, and in one study modeling the costs of adverse effects of medications, adherence accounted for the largest fraction of the total costs.⁶ While the degree to which sustained-release preparations improve adherence is unclear, the potential benefits are clearly large. Moreover, sustained-release preparations can have physiological benefits; for example, for calcium-blockers the sustained-release preparations do not appear to be associated with increased risk of myocardial infarction, as were some short-acting preparations.⁷

Yet there is also a dark side to sustained-release medications. Most sustained-release drugs have the same name as the short-acting preparations, with an additional term such as “SR” for sustained release added. Because pharmaceutical companies have invested large sums in drug names, they have been reluctant to use different names for sustained-release preparations, although this has been done in some instances, e.g., with Tiazac. If the short-acting drug is given in the dose intended for the long-acting drug, a serious adverse drug event and even death can result. Nationally, a number of serious injuries, including deaths, have been attributed to this error.^8–11

In this study, Lesar found a large number of errors with sustained-release medications, among which 70% were failure to specify the sustained-release formulation of the product, which can be especially dangerous.⁵ Another 12% of these errors involved prescribing controlled-delivery formulations to be administered by tube, which can also result in adverse consequences, since the drug becomes immediately available when the medication is ground up.

These data have a number of implications regarding prevention of these errors. At the level of the Food and Drug Administration (FDA) and pharmaceutical manufacturers, the large number of errors and much smaller number of fatal adverse events suggest that giving long-acting and short-acting preparations similar names is a practice that should be seriously reconsidered, and probably abandoned. In particular, it is dangerous to have sustained-release preparations that are a multiple of the shorter-acting preparations.

At the individual provider level, prescribers should take extra caution when prescribing a drug that comes in both sustained-release and shorter-acting forms, and in particular make sure they specify that they are ordering the long-acting form if that is what they intend. Education regarding this may be helpful, as noted by Lesar.

However, using “extra caution,” and providing education about issues like this represent weak safety strategies. Much more effective will be computerizing prescribing, for both inpatients and outpatients. In one study, computerized physician order entry reduced the serious medication error rate 55% in inpatients.¹² In this particular situation, when clinicians are selecting a drug, they can be shown the available preparations, which probably increases the likelihood that they will select the intended form (because they can see the options). In addition, individual orders can be checked for overly high doses and for prohibited routes (e.g., giving a sustained-release preparation via a tube). Computerizing ordering is not a panacea in this regard; such systems must contain decision support to catch such errors, and the available commercial applications vary widely in the degree of decision support they include.¹³

Berwick has suggested that improving safety will require moving ahead “by taking one hill at a time”¹⁴; one such hill is sustained-release medications. Like most of these hills, it is complex, and there is an array of issues, but they are addressable. Careful serial scrutiny of the entire mountain range will eventually result in substantial improvement in patient safety.