XL or Smaller?
With a history of hypertension and chronic renal failure secondary to hemolytic uremia syndrome at age 3, a 14-year-old boy presented to the emergency department with dehydration secondary to gastroenteritis. Though his gastroenteritis had resolved, he was admitted due to worsening renal function and out-of-control hypertension.
The intern admitting the patient spoke with the renal fellow to ask for advice concerning the hypertension, which now measured 160/95. The renal fellow recommended giving the patient Procardia® (nifedipine) 30 mg by mouth. The intern wrote an order for the medication. Approximately 45 minutes later, the nurse paged to inform the intern that the medication had been given and inquire how often the blood pressure should be checked. The intern’s senior resident happened to be present. As the scenario was discussed, the senior realized that 30 mg of Procardia, not Procardia XL® (extended-release nifedipine), had been given. The nurse was asked to check the blood pressure every 3 minutes, and the residents immediately went to see the patient.
Within 5 minutes, the patient’s blood pressure had decreased to 110/60. IV fluids were started and the renal fellow was contacted. Glucagon was brought up to the bedside but did not need to be administered, as the patient’s blood pressure did not drop below 100/50 and he remained asymptomatic while supine.
Upon further discussion between the fellow, intern, nurse, and pharmacist, several points emerged. When renal specialists refer to the extended-release drug Procardia XL, it is often called Procardia 30 mg, to differentiate it from Procardia 5 mg, the instant-release formulation used in hypertensive crisis. The pediatric intern had minimal experience dealing with hypertensive medications, and did not recognize the difference when the fellow recommended Procardia 30 mg. The nurse had consulted a drug reference and had seen that Procardia was typically given as 5 mg, but that a 30 mg dose was available. She then discussed the order with the pharmacist. The pharmacist had seen that the medication was written as Procardia, and not as Procardia XL. However, after talking with the nurse, who confirmed the patient had significant hypertension currently refractory to his normal hypertensive medications, he concluded that Procardia was indeed the desired medication.
Calcium channel blocker overdose can lead to serious complications, mainly bradycardia and hypotension. In severe cases, the outcome can be fatal. In 2001, 50 cases of death due to calcium channel blockers were reported.(1) Some of these cases, like the case presented, were due to therapeutic errors.
This case is an example of an error resulting from using the wrong dosage form—ie, failure to specify that a controlled-release formulation should be used. Other examples of errors resulting from using a wrong dosage form include giving a controlled-release formulation through a tube (the drug is crushed and therefore will have an immediate effect), prescribing a controlled-release formulation on an “as needed basis,” and giving a subcutaneous (SC) formulation intramuscularly (IM). These errors are not uncommon among inpatients. In one study (2), more than 10% of errors in a large teaching hospital were attributed to a wrong dosage form. The number of dosage form errors occurring in outpatients is unknown. Lesar (3) found that from 1996 to 2000 the number of such errors increased and that one in every 100 admitted patients may encounter such errors. Almost 70% of the errors in that study involved failure to specify a controlled-release formulation, and another 12% giving a controlled-release preparation through a tube. The increase in errors involving medication dosage forms may be due to increasing usage of controlled-release preparations. Compared with immediate release formulations, controlled-release formulations may improve patients’ adherence to treatment, improve clinical outcomes, and reduce health costs.(4) Yet, as this case demonstrates, using different dosage forms bears its own risks.
That the drug was ordered by its brand name (Procardia) and not by the generic name (nifedipine) may have contributed to the error. Indeed, using a brand name has generally been considered a major risk for medication errors (5), although one recent study (3) found equal numbers of errors when using the generic name or the brand name.
Using the wrong dosage form is by far less common in pediatrics, where the most common type of errors are dosing errors (6-8), than in adult medicine. There are several reasons why such errors are rare in pediatrics. Since infants and young children are unable to swallow tablets and capsules and take oral medication mostly in liquid formulation, controlled-release preparations are not commonly used. Another reason is that cardiovascular drugs, hormonal replacement therapy, and psychiatric drugs, which are often given in a controlled-release formulation, are less commonly used in infants and young children.
Several features of this case are characteristic of the circumstances in which drug errors occur. For example, the prescribing physician was a first-year resident. Previous studies have demonstrated that less experienced physicians are more likely to err.(7,9) The drug involved in this case was an antihypertensive drug not commonly used by pediatricians. The lack of knowledge and the application of knowledge regarding a specific drug therapy is another risk factor for medication error.(10)
This case can be viewed as a prescribing error by the resident. It can also be considered a transcription error, in which the error occurred when the resident wrote the verbal order given by the senior physician. Verbal commands, transcribed by nursing staff, are a risk factor for medication errors.(11) Whether this was a prescribing or transcription error, other checkpoints along the way (ie, the dispensing and administration of the drug) failed either to recognize that an error occurred or to prevent it from reaching the patient. These include the pharmacist, who despite recognizing the dose as unusual for immediate-release nifedipine did not confirm the order with the prescribing physician, and the nurse who gave the drug despite her concerns about the dose. These lapses highlight the importance of all providers maintaining vigilance for the possibility of error—and acting on potential error signals when detected, rather than dismissing them.
How could this error be prevented? Some risk factors cannot be avoided. There will always be first-year residents and some drugs are infrequently used. Although lack of knowledge has been repeatedly identified as a contributing factor for medication errors (10,12) and special programs to improve prescription-writing abilities of residents may reduce prescription-writing errors (13), such measures will not resolve this issue. Ensuring that junior doctors carry a reliable and easy to use source of information on prescribing, such as a hospital formulary or a handheld computer (14), might be a better strategy.
Using computerized order entry (CPOE) could probably prevent such an error. However, only a small fraction of hospitals in the USA have such systems in place. A hierarchical medical team, in which communication flows in one direction, has been suggested as a contributing factor to errors. Improving communication between team members has been advocated as an effective strategy to reduce errors in medicine.(15) Drug regulatory agencies should consider requiring companies to give different brand names to different formulations of the same drug. Although the practice of using a similar trade name for long- and short-acting preparations saves the pharmaceutical industry money in advertising and marketing, it can be dangerous, as demonstrated by this case.
Eran Kozer, MD Pediatric Emergency Medicine Assaf Harofeh Medical Center Zerifin, Israel
1. Litovitz TL, Klein-Schwartz W, Rodgers GC, et al. 2001 annual report of the american association of poison control centers toxic exposure surveillance system. Am J Emerg Med. 2002;20:391-452.[ go to PubMed ]
2. Lesar TS, Lomaestro BM, Pohl H. Medication-prescribing errors in a teaching hospital. A 9-year experience. Arch Intern Med. 1997;157:1569-1576.[ go to PubMed ]
3. Lesar TS. Prescribing errors involving medication dosage forms. J Gen Intern Med. 2002;17:579-587[ go to PubMed ]
4. Cramer MP, Saks SR. Translating safety, efficacy and compliance into economic value for controlled release dosage forms. Pharmacoeconomics. 1994;5:482-504.[ go to PubMed ]
5. Schwab M, Oetzel C, Morike K, Jagle C, Gleiter CH, Eichelbaum M. Using trade names: a risk factor for accidental drug overdose. Arch Intern Med. 2002;162:1065-1066.[ go to PubMed ]
6. Kaushal R, Bates DW, Landrigan C, et al. Medication errors and adverse drug events in pediatric inpatients. JAMA. 2001;285:2114-2120.[ go to PubMed ]
7. Kozer E, Scolnik D, Macpherson A, et al. Variables associated with medication errors in pediatric emergency medicine. Pediatrics. 2002;110:737-742.[ go to PubMed ]
8. Selbst SM, Fein JA, Osterhoudt K, Ho W. Medication errors in a pediatric emergency department. Pediatr Emerg Care. 1999;15:1-4.[ go to PubMed ]
9. Lesar TS, Briceland LL, Delcoure K, Parmalee JC, Masta-Gornic V, Pohl H. Medication prescribing errors in a teaching hospital. JAMA. 1990;263:2329-2334.[ go to PubMed ]
10. Lesar TS, Briceland L, Stein DS. Factors related to errors in medication prescribing. JAMA. 1997;277:312-317.[ go to PubMed ]
11. Fijn R, Van den Bemt PM, Chow M, et al. Hospital prescribing errors: epidemiological assessment of predictors. Br J Clin Pharmacol. 2002;53:326-331.[ go to PubMed ]
12. Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drug events. ADE prevention study group. JAMA. 1995;274:35-43.[ go to PubMed ]
13. Shaughnessy AF, D'Amico F. Long-term experience with a program to improve prescription-writing skills. Fam Med. 1994;26:168-171.[ go to PubMed ]
14. Rothschild JM, Lee TH, Bae T, Bates DW. Clinician use of a palmtop drug reference guide. J Am Med Inform Assoc. 2002;9:223-9.[ go to PubMed ]
15. Sexton JB, Thomas EJ, Helmreich RL. Error, stress, and teamwork in medicine and aviation: cross sectional surveys. BMJ. 2000; 320:745-749.[ go to PubMed ]