• Cases & Commentaries
  • Published June 2004

Dangerous Dapsone

The Case

A 78-year-old woman with newly diagnosed multiple myeloma on corticosteroids presented to the emergency department with dyspnea. Upon admission, she was found to be hypoxic, and she required increasing amounts of oxygen to maintain saturations greater than 90%. However, her arterial blood gas (ABG) showed a paO2 of > 430 on 100% O2, with no A-a (alveolar-arterial) gradient. The next day, she was found to be cyanotic on morning rounds, and a stat ABG showed methemoglobinemia of 30%.

The etiology of her methemoglobinemia was determined to be incorrectly dosed dapsone for Pneumocystis carinii pneumonia (PCP) prophylaxis. The patient had seen her oncologist the week before admission, who had erroneously written her dapsone prescription as "100 mg TID", instead of TIW (Mondays, Wednesdays, and Fridays). Of note, on admission, the inpatient pharmacy had called the admitting team about the inappropriately dosed dapsone. However, because the patient's family had a copy of the original prescription from the oncologist, the admitting team assumed that the dose was correct and rewrote the medication order at the erroneously high dose. Fortunately for this patient, this mistake did not cause her adverse long-term clinical consequences. Once the error was discovered, the patient was promptly started on cimetidine 300 mg IV daily, and her methemoglobinemia resolved 7 days after admission.

The Commentary

Many well-known factors contributing to drug therapy mishaps or misadventures were likely at play in this case. First, the patient's oncologist may have been unfamiliar with the medication and may also have erroneously transcribed "TID" for "TIW." Second, the community pharmacy dispensed an incorrectly ordered medication. Third, despite an intervention attempt by the inpatient pharmacist, the house staff incorrectly ordered the medication to be continued. Beyond these considerations, communication and culture may have played an additional, subtler role in producing this unfortunate outcome.

If unfamiliar with prescribing dapsone for prophylaxis, the oncologist was not alone. Physicians of all types may be called upon to write prescriptions for unfamiliar drugs. The injunction to be conversant with all drugs prescribed is axiomatic but probably unrealistic. Many print and online references are available that provide prescribing information. In addition, community pharmacies are required to have updated references on hand to answer dosing and pharmacology questions. Physicians should regularly use these or similar resources. If the error were one of transcription, electronic transmission might have helped prevent the error, but direct communication by phone appears to be the best strategy. In one analysis of prescriptions requiring clarification, while faxed and written prescriptions required clarification most frequently, electronically transmitted prescriptions were more likely to be unclear than those received by telephone.(1) One would hope that the community pharmacy tried to reach the physician by phone to clarify the order. However, no matter which of the potential problems resulted in the error, the outpatient pharmacy should not have dispensed the medication as written.

In this case, the dispensing error was made at the community pharmacy; unfortunately, we have limited data why such errors occur. Error rates ranging from about 3.2% to 12.4% have been documented; factors that have decreased error rates include good lighting, fewer distractions and interruptions, reductions in ambient noise, and workload reduction.(2-5) Some have called for a limit to the number of prescriptions a pharmacist may fill on each shift.(3) A survey of community pharmacists confirms that they perceive environment and workload as major contributors to dispensing errors.(6) Many corporate pharmacies add additional production pressure by triggering computer alerts (a flashing light or prompt) when allotted time requirements for filling a prescription are not met. The pharmacy is then "graded" by production, rather than quality. An "attitude-behavior" study from Canada showed that pharmacists have good attitudes (self efficacy) about pharmaceutical care, but feel that they have little control over their work environment or ability to provide that care.(7)

Data on cisapride dispensing further confirms that a lack of environmental control may lead to potential dispensing errors. In a large managed care database, cisapride was dispensed along with an interacting, contraindicated drug 3.4% of the time. Of the contraindicated pairs, 89% were dispensed by the same pharmacy and 17% on the same day.(8) The time pressure to fill other prescriptions was often cited as a reason for dispensing these interacting combinations. Similar data was published in Europe.(9,10) These analyses are not able to report whether pharmacists attempted to prevent the problem. For example, they may have instructed the patient to discontinue cisapride while taking the interacting drug (macrolides, etc.); therefore, no data regarding the nature and impact of the intervention could be offered. Nor do these studies reflect how many times pharmacists may have stopped the interacting combination from reaching patients.(11)

A system that allowed pharmacists to document interventions that prevent adverse drug events and to be reimbursed for such interventions would not only provide much needed data, but also provide an incentive to perform the tasks necessary to intervene (profile review, interaction checks, etc.).

Had communication been more effective in this case, the error could have been mitigated. A recent study showed that medical residents perceive poor communication to be one of the most common contributing factors to medical mishaps.(12) Communication is not just the simple transmission and receipt of information. It involves labor and hierarchical divisions that often serve as barriers to complete communication. Personal ability and attention to important detail may improve communication markedly. Written communication is "an impersonal medium with limited capacity for timely feedback, [and] is seldom the most effective way to communicate a plan of action."(12) Thus, order writing (manually or electronically) may not be an ideal way for pharmacists and physicians to communicate. Even if person-to-person communication occurs, as it did in this case, communication may be ineffective when there is a perceived authority gradient. One wonders whether the resident in this case sensed that the oncologist had greater "authority" than the pharmacist, and therefore decided to adhere to the order as prescribed. Such perceptions of hierarchy may have contributed to the error. Formal training in effective communication may mitigate these types of errors.

Nonetheless, as with the outpatient pharmacy, the medication should not have been dispensed in the hospital. Clinical pharmacists have a positive impact on adverse drug events (13,14), yet in this case a phone call from a centralized pharmacist did not prevent the error. Had the residents used computerized physician order entry, they would have been blocked from ordering the incorrect dose, which might have compelled them to call the oncologist. Moreover, having a clinical pharmacist as a team member serving on the wards has been demonstrated to improve medication safety.(13,14) Had such systems been available at this institution, the error could have been prevented.

Take-Home Points

  • Prescription writing is an intricate professional task and it is essential to be precise. Avoid using potentially confusing abbreviations. Use available resources, including the pharmacist and/or text or web-based references, before prescribing an unfamiliar drug.
  • Pharmacists should not dispense any drug based on a prescription without data that support its use in the manner prescribed. When possible, pharmacists should be provided patient data related to the medications they are asked to dispense.
  • Pharmacists should work in well-lit, quiet areas, with minimal distractions. They should have greater opportunities to participate in deciding appropriate workloads and professional environments.
  • Pharmacists should be required to document their interventions to prevent adverse drug events, and should be reimbursed for appropriate interventions. To accomplish this task, the Health Care Financing Administration should recognize pharmacists as health care providers.
  • Communication problems may lead to errors. Potential solutions include: verbal communication when possible (pharmacists should be available on hospital floors), a less hierarchical workplace environment, and techniques to insure accurate communication (read back, legible handwriting, computerized physician order entry).

Tom Bookwalter, PharmD
Clinical Pharmacist
University of California, San Francisco


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14. Kucukarslan SN, Peters M, Mlynarek M, Nafziger DA. Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units. Arch Int Med. 2003; 163:2014-2018.[ go to PubMed ]

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