Drug Prescribing Errors: Summary

Poor penmanship was once the bane of prescribing, and the cause of many prescribing errors. Even as electronic prescribing (eRx) has markedly reduced some types of errors,[1] others have cropped up to take their place,[2] and the benefits of eRx are at risk of being overshadowed by unintended consequences.[3]

Recent reports of prescribing errors vary widely, from 5% to 81% of prescriptions.[3,4] A significant proportion of errors are believed to be caused not by system design features or software glitches, but by human factors, such as fatigue, selecting the wrong option, or entering the wrong patient information into an often cumbersome system. And although most prescribing errors are detected and resolved by pharmacists in both the inpatient and community settings,[5-7] some still slip through the entire medication use chain, making it all the way to the patient.

The five main categories of traditional prescribing errors are wrong patient; wrong drug; wrong dose, strength, or frequency; wrong drug formulation; and wrong quantity. In a recent study,[3] the four most common errors observed were wrong drug quantity (40%), wrong duration of therapy (21%), wrong dosing directions (19%), and wrong dosage formulation (11%).

The following serious prescribing errors are consistent with these traditional categories, although with various twists introduced by eRx. These errors, collated from the literature, patient safety experts, and the Institution for Safe Medication Practices (ISMP), are not ranked in any way, but simply represent a sample of potentially serious errors in contemporary drug prescribing.

Prescribing the Wrong Drug

At an outpatient clinic, a clinician used an eRx system to order an antibiotic for a child whose throat culture was positive for group A streptococci. She intended to prescribe penicillin, but accidentally selected penicillamine (a chelating agent used to treat Wilson disease) on the drop-down drug list. The prescription was dispensed by a community pharmacist, and the child received penicillamine 250 mg by mouth twice a day for 2 days. His father noticed that his son appeared pale and sleepy, and his strep throat did not seem to be improving. He showed the medication bottle to the pharmacist, and the error was discovered. The child was treated at the local emergency department.[8]

Some eRx systems autopopulate or present a drop-down menu after the first few letters of the desired drug are typed into a search field, at which point a prescriber might inadvertently select the wrong medication.[1] It is believed that this was one cause of recent prescription and dispensing errors reported to the US Food and Drug Administration involving Brintellix® (vortioxetine, a serotonergic agonist/antagonist) and Brilinta® (ticagrelor, a platelet inhibitor).

The prescriber knows what drug he or she wishes to prescribe. The error comes in trying to convey this to another healthcare provider, such as a pharmacist or nurse. This can occur when the prescriber's handwriting is less than crystal-clear, as in the photo above. The pharmacist or nurse misreads the prescriber's handwritten prescription, the mind substituting a similar-looking drug, and a wrong drug medication error is born. In the illustration here, the intended drug PreNexa® was misread as Ranexa®, and the latter was dispensed. Illegibility continues to be a significant source of prescribing error in ambulatory settings.[10]

The 21st-century equivalent of poor penmanship is the long list of look-alike, sound-alike (LASA) drugs on a drop-down screen. The prescriber opens a menu of drugs (many of which have similar or identical stems) and inadvertently selects the wrong drug, frequency, or quantity; this order is then transmitted to the pharmacy. If the system does not require the prescriber to enter an indication for the drug, it is difficult for a pharmacist to know that the wrong drug has been ordered.

ISMP recommends "Tall Man lettering" (mixed case or capitalized letters within drug names to highlight primary dissimilarities with look-alike drug names, such as hydrOXYzine and hydrALAZINE) as a means of reducing the risk for drug selection errors.[10] It also helps to include both the brand name and generic name on prescriptions. Most LASA drugs also have different indications, so indication prompts can be useful to intercept drug selection errors.[11] Where possible, practices should consider limiting the number of drugs that show up on drug selection menus to those that are most commonly prescribed in that practice.

Formulation Blunders

Drug modifiers for different drug formulations are common,such as the once-daily formulation Wellbutrin XL® (bupropion extended-release) and Wellbutrin SR® (bupropion sustained-release), which is indicated for twice-daily dosing. Wellbutrin mix-ups are especially likely because both the SR and XL formulations are available in 150-mg tablet strengths, and it's not unusual for the SR formulation to be prescribed once daily.

The anticonvulsant agent Depakote® is another drug with multiple modifiers. It is available as delayed-release capsules (Depakote Sprinkles), delayed-release tablets (Depakote), and extended-release tablets (Depakote ER).

A clinician intended to prescribe 1500 mg of Depakote ER to a patient with a seizure disorder. However, several formulations of Depakote (delayed release, extended release, tablets, and capsules) were listed on the drop-down menu, and the clinician selected delayed-release instead of extended-release. Nine hours later, the patient received the full 1500-mg dose of Depakote at once, because the full dose of delayed-release Depakote enters the circulation more rapidly than the extended-release formulation. The patient developed significant hypotension and sedation but eventually recovered.

Many prescribers and pharmacists have noticed the high potential for confusion among the various formulations of drugs, and errors of formulation selection are common.[13,14] The modifiers for short-acting, intermediate-acting, and long-acting formulations are not standardized in the industry. ER (extended-release) may mean a 24-hour formulation for one drug and a 12-hour formulation for another drug. The United States Pharmacopeia defines delayed-release tablets as enteric-coated, intended to delay the release of the medication until the tablet has passed through the stomach to prevent the drug from being inactivated by gastric secretions or to prevent gastric mucosa irritation. Extended-release tablets are formulated to make the drug available over an extended period after ingestion. The delayed-release formulation of Depakote is enteric-coated, whereas Depakote ER is not enteric-coated. They are not bioequivalent or interchangeable.[12] Another agent that is often involved in serious formulation prescribing errors is insulin.[15]

As more drug product lines expand to offer different formulations, this type of error could become more common. The best way to prevent such errors is to become familiar with the different modifiers on prescribed medications. Be explicit in the dosing directions for the frequency that you want the medication taken, and tell the patient exactly how it should be taken. Most often, if a mistake is made, the pharmacist will contact the prescriber because the frequency is not consistent with the formulation.

Alert Madness

A 33-year-old woman with refractory epilepsy was admitted to the hospital with increasing frequency of seizures. Her seizures were controlled with fosphenytoin, and she was discharged 2 days later with a prescription for phenytoin, 500 mg once daily. However, the clinician inadvertently failed to change the default frequency (three times daily) to the desired frequency of once daily, and ignored an overdose alert triggered by the excessive daily dose. In this case, the pharmacist also missed the high-dose alert, and dispensed the phenytoin with instructions to take three times daily. The patient took the phenytoin as instructed for a few days, but when she began having trouble walking, the error was discovered. The patient experienced transient phenytoin toxicity.[

presented during the order entry process also can interfere with the prescriber's concentration, increasing the likelihood of error.[17]

Most alerts (even those warning of high-severity drug interactions) are rejected or ignored by clinicians.[18,19] In one recent study,[19] 93% of drug/drug interaction and drug-allergy alerts were overridden. Too many alerts with low credibility can induce prescribers to override important alerts along with false-positives,[18] a phenomenon known as "alert fatigue."[20]

Perhaps nowhere is the human/computer interaction as important as in the prescriber's response to alerts. This case demonstrates that prescribers can become desensitized to alerts. To minimize this, alerts in the eRx system must be both sensitive and specific, and only alerts that warn of potential errors should be presented, not irrelevant or redundant messages.[16] The threat of missing a rare event must be balanced with the dangers of burdening clinicians with unnecessary and interruptive electronic alerts.[21] The credibility of prescribing alerts can be improved by reducing alerts that contradict broadly accepted clinical practices.[17] It is also recommended that alerts be tiered according to severity, and that they be presented to prescribers at an appropriate place in the workflow to improve prescribing efficiency.[19,22]

And what, if anything, would prescribers like to see more alerts for? Lab values, and a list of drugs prescribed for the patient by other providers.[17]

Failure to Adjust

A 71-year-old woman receiving palliative chemotherapy for lung cancer developed methicillin-resistant Staphylococcus aureus bacteremia. Vancomycin 1.25 g was given, and she was transferred to a referral hospital. Her serum creatinine level at the community hospital was 0.4 mg/dL, and at the referral hospital, it had doubled to 0.8 mg/dL (although this was still within the normal range). Vancomycin was continued. By the next day, she was in acute renal failure with an elevated creatinine level. A vancomycin trough level was obtained, and reported as 64 mg/L. Her renal failure worsened; she became anuric and required urgent dialysis.[23]

Vancomycin is renally eliminated and has a narrow therapeutic index with a high potential for nephrotoxicity. The admitting clinician neither recognized the doubling of this patient's serum creatinine level nor ordered a vancomycin trough level.

Chronic kidney disease (CKD) is an increasing concern in elderly persons.[24] Senile pharmacokinetic changes in the kidney include dysautonomia; glomerular filtration rate reduction; tubular back-filtration; sodium, calcium, and magnesium loss; potassium retention; altered dilution-concentration capability; and tubular frailty.[25] Furthermore, elderly patients are frequently on multiple medications to manage their many comorbid conditions. The early stages of CKD are often unrecognized, placing the elderly person at high risk for serious, yet largely preventable, drug-related safety events.[26,27] Indeed, inappropriate prescribing of renally cleared drugs is common in adults.[28,29] A recent study identified perindopril, fenofibrate, glibenclamide, gliptins, metformin, olmesartan, bisphosphonates, and strontium as drugs frequently prescribed to elderly adults without evaluation of renal function.[29]

It is essential to consider renal function when prescribing renally cleared drugs in this population and make appropriate dosage adjustments.[30] Either the Cockcroft-Gault equation or the Modification of Diet in Renal Disease (MDRD) study equation can be used for routine estimation of glomerular filtration rate (GFR), although the MDRD is considered superior in patients with low GFR (< 60 mL/min/1.73 m2).[31,32] The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults,[33] issued by the American Geriatric Society (AGS), is also an important resource when prescribing for older adults. AGS released updated criteria in 2015.

Phoning It In

A 56-year-old man was hospitalized for replacement of a percutaneous endoscopic gastrostomy tube. He was on warfarin owing to a history of intracardiac mural thrombus, but his international normalized ratio (INR) was low. His medical team decided to increase his warfarin from 5 mg/day to 10 mg/day for 3 days to raise his INR. Later that day, on review of his case, it was decided to stop warfarin altogether until an echocardiogram could be obtained to evaluate whether he still had intracardiac thrombus. The resident started to enter the order into his smartphone but was interrupted by a personal text. After answering the text, he forgot to complete the order to discontinue warfarin. As a result, the patient continued to receive 10 mg daily. On the fourth day, he experienced shortness of breath, tachycardia, and hypotension. An echocardiogram showed hemipericardium and tamponade, requiring emergency open heart surgery.[34]

As of 2014, smartphones were being used by one third of physicians to prescribe.[35] The use of such mobile devices as smartphones and tablets can increase the convenience of prescribing, but not without a cost to patient safety. Having clinical information and decision support at one's fingertips could improve the timeliness of care, but mobile technologies also pose such risks as transmission of infection; interference from electromagnetic radiation; breach of confidentiality; multitasking, and as shown in the case, interruption and distraction.

Institutions are challenged to develop policies and technologies for mitigating the risks associated with mobile prescribing, to capture their benefits while reducing their harm.[34] However, the safe use of mobile devices falls heavily on the shoulders of individual prescribers, to ensure that personal communications or interruptions do not pose risks to patient safety.

Errors In, Errors Out

A 17-month-old toddler was brought in to the emergency department for evaluation of an eye infection. The nurse weighed the toddler and recorded the weight in the chart. However, the nurse entered "25 kg" instead of "25 lb" (11.3 kg). The physician prescribed clindamycin 225 mg orally three times daily, calculated using the weight of 25 kg, and the first dose was given before discharge. The child's mother noticed the incorrect weight on the discharge paperwork, and the dose was corrected. The child suffered only diarrhea from the incident.[36]

Wrong, outdated, or missing information can result in myriad prescribing errors. Patient information that is critical to prescribing includes allergies, medical history, current medication list, body weight, and laboratory data. Body weights should always be recorded using the metric system, because that is how drugs are dosed. When such information is missing or out of date, errors in prescribing may follow. In one incident, staff failed to record in the chart that a woman with chronic asthma was pregnant, and she was given bronchodilators, corticosteroids, and intravenous levofloxacin (a pregnancy category C drug).

Ambiguous Abbreviations

To save time, prescribers often will use abbreviations, especially in handwritten prescriptions. Prescribers may abbreviate a long drug name, use an often misunderstood symbol, or use abbreviations for dosing or administration instructions. This category of error also includes misuse of decimals (leading and trailing zeros) and other symbols. These shortcuts might save the prescriber a few seconds of writing, but can spell confusion for other healthcare professionals downstream and potential harm for the patient. Abramson and colleagues[37] found a very high rate of abbreviation errors in their study of outpatient prescribing errors.

In the cases illustrated in this slide, the first prescriber (top) intended for the order to read "Dilaudid 0.6 mg Q 10′ PRN (every 10 minutes as needed)," but it was read as "Dilaudid 0.6 mg QID PRN (4 times daily as needed)." The second prescriber (middle) intended to prescribe potassium chloride QD (daily), but the prescription was misread as QID (4 times daily). The use of "Pot" as an abbreviation for potassium is also error-prone and is not recommended. The order for vincristine (bottom) was intended to be a dose of 0.4 mg, but the decimal point was misplaced and barely visible. It was read as "4 mg vincristine." This type of error can be prevented by using a leading zero for doses less than one.

eRx is not immune to confusion from error-prone abbreviations. In some electronic systems, decimal points are difficult to visualize, making wrong dose selections more likely.

Drug name abbreviations are often confused (eg, MgSO4 for morphine). The simplest way to avoid misinterpretation of drug name abbreviations is to fully spell out drug names and directions. If abbreviations must be used, use only standard abbreviations approved by the acute care institution and avoid abbreviations completely for outpatient prescriptions. ISMP provides a list of error-prone abbreviations, symbols, and dose designations, and the Joint Commission has a "Do Not Use" list. These include the commonly used abbreviations µg, OU, and D/C, which should instead be written as "mcg," "both eyes," and "discharge" (or "discontinue"), respectively.

More Errors

Wrong patient. An emergency medicine physician inadvertently switched medication orders on two patients. One was in the emergency department for intravenous hydration, and the other had been in a motor vehicle accident and was going to be intubated and transferred to a trauma center. Because of the switch, the hydration patient received midazolam and vecuronium, went into respiratory arrest, and died.[38]

Wrong patient errors are being reported more frequently with eRx. In the pre-electronic era, unless it was a telephone order, the prescriber had to be physically present on the unit, because that is where the chart was located. With computerized charting, it is possible to have several patient files open at the same time and inadvertently click on the wrong chart to enter the order. Alternatively, the prescriber is on a different unit, and enters a remote order on the wrong patient because of similarity in patient names.

Some wrong patient errors can be prevented by limiting the number of charts or files that can be open at one time.[38] Many electronic health records (although not all) have this feature built in. An exception is often made for the emergency department.

Wrong dose or frequency selection. Like picking the wrong drug, clicking on the wrong dose or frequency from the numerous choices typically displayed on drop-down menus can easily occur. Sometimes, prescribers have entered the wrong frequency, or left the default frequency and used a comment field to communicate the correct information through free text. These instructions may be ambiguous or confusing and, furthermore, often appear several screens after the main screen and are easily overlooked by the pharmacist. The drug is then dispensed with the wrong or the default frequency.

Errors in dose calculation. A potentially serious prescribing error is miscalculating a dose, especially with weight-based dosing. Historically, "decimal point errors" made during calculations have been responsible for serious prescribing overdoses in neonates and children.[39]

Failure to Deprescribe

An 86-year-old woman is seeing a new healthcare provider because her previous provider has retired, and she is experiencing pain, insomnia, and diarrhea. She is being treated for mild heart failure secondary to valve disease, hypertension, hyperlipidemia, glaucoma, depression, chronic kidney disease, and diabetes. She reports an increase in dizziness as of late; she is having trouble getting into and out of the bathtub. She knows that she takes a handful of pills daily but is not sure what they are for. Her healthcare provider looks at her current medication list, and although he realizes that this list represents polypharmacy, he is reluctant to change anything at this time because he is not familiar with her history and why she is taking these medications. Instead, he refills several of her medications. Two days later, the woman gets up during the night because she can't sleep, intending to make some tea. She is dizzy, and falls and breaks her hip and her humerus, requiring surgery.

Some experts distinguish between prescribing errors and prescribing faults. Prescribing errors are those made in the act of writing or entering a prescription, whereas prescribing faults include irrational prescribing, inappropriate prescribing, underprescribing, overprescribing, and ineffective prescribing, as a result of erroneous medical judgement, treatment decisions, or treatment monitoring.[40]

Deprescribing is the act of tapering, reducing, or stopping a medication.[41] The failure to deprescribe ("prescribing inertia") is a prescribing fault that is especially dangerous in the elderly population, who might already be taking a handful of pills every day. When a new drug is prescribed, the risk for drug/drug interactions and adverse events rises.[42] Polypharmacy in older adults is associated with, at the very least, falls, cognitive impairment, and increased mortality.[43-45]

Barriers to deprescribing include ambivalence about stopping medications, reticence to stop medications prescribed by others, limited knowledge about best practice for stopping medications, and concern about potential withdrawal.[41] However, deprescribing has a major benefit for eRx because it can reduce the number of pesky alerts about potential drug interactions.

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Published on Medscape:  October 22,2015  Authors: Graham, LR, Scudder L, Stokowski L