An alphabet soup of suffixes has arisen for controlled-release drugs, increasing the potential for drug errors
In recent years, the number of sustained-release drugs on the market has skyrocketed, as pharmaceutical companies try to design formulations that require fewer daily doses, deliver drugs more consistently over time, or reduce side effects. But as the number of products has risen, so has the potential for errors, warned Michael R. Cohen, R.Ph., M.S., D.Sc., president of the Institute for Safe Medication Practices (ISMP).
While the abbreviations used to denote sustained activity refer to different technologies with different characteristics, they have no specific meanings and appear to be randomly chosen, Cohen said. This leads to confusion among physicians, pharmacists, and patients. Consider the following alphabet soup of suffixes: XL, SR, CD, LA, XT, to name just a few.
When a pharmacist dispenses an immediate-release formulation at a dose intended for sustained release, the outcomes may result in increased therapeutic or adverse effects and possibly a reduced duration of those effects, said Timothy S. Lesar, Pharm.D., director of pharmacy at Albany Medical Center. Such dispensing errors are most likely to occur when regular and extended-release forms of drugs are available in the same dosage strengths or when the extended-release dose can be made up by multiple tablets or capsules of the standard-release formulation, he explained.
There are several ways in which the gap between prescribers' intentions and pharmacists' dispensing can lead to medication errors. Often, physicians neglect to add the suffix to a drug's name, Cohen said. Even when prescribers correctly designate the formulation, misunderstandings can occur during telephone transmission of prescriptions. "For example," Cohen said, "XL can easily sound like SL, and an immediate-release formulation could be given under the tonguesublingually." He reported one such case of a patient who wound up in the ICU with acute hypotension after receiving 90 mg of immediate-release Procardia (nifedipine, Pfizer) sublingually instead of the intended Procardia XL (nifedipine extended release, Pfizer) 90 mg.
"In a handwritten prescription, XL could look like x1 [times one]," Cohen continued. And hospital pharmacists might misinterpret this to mean that the immediate-release form of a drug should be given once. The availability of multiple sustained-release formulations of the same drugwhat he calls "long-acting and longer-acting"complicates matters further. The products use different technologies and, thus, have different release rates and other characteristics.
A quick glance at the name of a product gives no indication of how it should be dosed. "XL doesn't necessarily mean once a day," Lesar noted. An extended-release product may be dosed twice daily, or it may be given the same number of times per day as the immediate-release form but with less of a peak effect, he explained.
Pharmacists who do not recognize a drug named on a prescription may dispense a drug with a similar-sounding nameoften a product with the same active ingredient but different release characteristics. "These drugs are coming out so quickly that you don't know what's in what anymore," Lesar lamented.
ISMP has received reports of pharmacists mistaking scripts for the new once-daily Depakote ER (divalproex sodium extended-release, Abbott) for the original Depakote (divalproex sodium, Abbott)itself a delayed-release preparationbecause they were unfamiliar with the new longer- acting product. Similarly, pharmacists have misinterpreted prescriptions for the new once- daily Metadate
CD (methyl- phenidate HCl extended release, Celltech Pharma) and dispensed Metadate ER (methylphenidate HCl extended release, Celltech Pharma), which is taken two to three times daily. Cohen anticipates similar confusion to occur between the new methylphenidate product Ritalin LA (Novartis) and previously available Ritalin SR (Novartis).
Generic forms of sustained-release products further muddy the waters. Often, Cohen said, generic companies "come up with another brand name that we now have to remember, and it can be confused with something else." The calcium-channel blocker diltiazem, for example, comes in several different sustained-release capsules. Although both Cardizem CD (Biovail) and Dilacor XR (Watson) are q.d. dosage forms, they are not interchangeable. However, Cartia XT (Andrx) is a generic form bioequivalent to Cardizem CD, while Diltia XT (Andrx) is bioequivalent to Dilacor XR.
This can generate confusion, "particularly as people transition through different healthcare settings," Lesar said. For example, a patient who normally takes Cardizem CD may be given the equivalent Cartia XT while hospitalized, and, upon discharge, may unwittingly fill a prescription for Cartia XT, even as he resumes taking the Cardizem CD he has at home.
During the administration phase, ignorance about extended-release products may lead to the disruption of their delivery processes, Lesar said. Patients may crush tablets or open capsules to take them with applesauce. Nurses may open capsules to administer via nasogastric tube, not realizing that the drugs are sustained-release formulations. Such mistakes are made more likely by the fact that suffixes tacked on to drugs' names do not always indicate extended-release properties, Lesar said. Because suffixes are not standardized, abbreviations may also refer to route of delivery (e.g., SL for sublingual), use (e.g., AD for antidiarrheal), or ingredient (e.g., DMdextromethorphan).
Controlled-release formulations differ not only in duration of action, but also in timing of administration and food effects, said James Polli, Ph.D., R.Ph., associate professor of pharmaceutical sciences at the University of Maryland School of Pharmacy in Baltimore. Some drugs, such as Covera HS (verapamil HCl extended release, Searle), are engineered with "a therapeutic goal in mind," he said, and have "pulsatile release." In the case of Covera HS, this means that, to work as intended, the drug must be taken at bedtime.
Food effects can also vary depending on the type of sustained-release technology, Polli said. "These effects are actually quite complicated and difficult to predict, and certainly very difficult to predict just from a name of a product," he said. Drug labeling is the only guide when it comes to determining whether a drug is best administered with or without food, he added.
What can pharmacists do to avoid errors? The No. 1 rule, experts say, is to be suspicious when looking at a prescription that seems unusual. "You really have to look at these [prescriptions] and ask, 'Could it be the other product?'" Cohen said. Speaking to patients may help elucidate matters, because sometimes they have marked down the name or dosing regimen of their drug or know what the medication should look like, he said. Both pharmacists and physicians should stress to patients "how critical it is for them to know the names of their drugs and ... to make sure that the pharmacist talks to them," he added. Patients should always be informed that they should not crush, chew, or open sustained-release formulations.
Vigilance can be effective only where there's knowledge, so pharmacists should keep abreast of new drugs coming onto the market. "Go through journals and look at ads," advised Lesar. "Because that's usually the first place you see these things." Pharmacists should read drug labeling carefully to determine how products differ from one another.
Simple changes in the pharmacy can also help heighten awareness. Cohen recommended flagging the vials of easily confused medications and posting notes in the computer system reminding pharmacists to check for common errors. Computer formularies should be set up so that drugs with the same name and different suffixes appear on the same screen"and make sure that the suffix actually fits in" and is not truncated, he cautioned.
Hospitals should institute policies that require pharmacy review when a patient's drugs are changed to per tube, so that sustained-release systems are not inadvertently disrupted, Lesar said. And educating the nursing staff and prescribers about extended-release drugs should be an ongoing effort.
Ultimately, though, Cohen believes that these errors can best be avoided if the Food & Drug Administration standardized the suffixes used in drug nomenclature. How can pharmacists lobby for such changes? By reporting errors when they occur, both Cohen and Lesar replied. Reports can be made to the FDA's MedWatch program or to ISMP; while MedWatch tends to collect more data before issuing warnings, Lesar said, ISMP responds quickly by alerting professionals and the public to potential errors.
Tzipora Lieder. Controlled-release abbreviations: Out of control?.