1. Cain, Joanna E. BSN, RN
  2. Kayyali, Andrea MSN, RN

Article Content


According to this study:


* Few patients experience consequent adverse events.


* Seven medications account for nearly three-quarters of all neglected warnings.


* 19.4% of patients did not receive proper monitoring.



The black box warnings on the labeling of prescription medications convey crucial information on the possible contraindications, serious adverse events, and monitoring needs that should be considered, and a recently published study reveals that 7% of 33,778 outpatients were prescribed medications in disregard or misapprehension of such warnings and that fewer than 1% of them suffered adverse events as a result.


More than 324,000 patients ages 18 and older who were seen in an outpatient care setting and prescribed a drug with a black box warning were included in the observational study. Data on medications prescribed, patient demographics, comorbidities, and the results of blood work were collected from 51 ambulatory practices, all of which stored their patient records electronically. The analysis focused on patients who were prescribed drugs bearing black box warnings concerning drug-drug interactions, drug-disease interactions (an adverse event occurring when a drug is prescribed despite the patient having a medical condition contraindicating its use), and drug-laboratory interactions (cases in which laboratory-monitoring recommendations aren't adhered to). The researchers evaluated whether prescribers' failure to adhere to such warnings resulted in adverse events. They randomly selected 575 medical records to review for the presence of medication errors, possible adverse drug reactions, and actual ones.


A total of 33,778 patients were prescribed medications with black box warnings during the one-year study period, a number representing approximately 10% of the total number of patients in the target population; the majority of the warnings (90.6%) applied to drug-disease interactions, followed by 26.6% concerning drug-laboratory interactions, and 3.3% concerning drug-drug interactions (some medications carried more than one type of warning). The researchers found that 36.2% of those who received drugs with black box warnings concerning drug-drug interactions were taking one of the contraindicated medications described in the black box warning. In regard to drug-disease interactions, only 0.7% of patients were found to have conditions for which the prescribed drug was contraindicated, and concerning drug-laboratory interactions, 19.4% of patients did not receive proper laboratory monitoring as indicated in a black box warning.


The researchers also discovered that white women ages 75 or older taking several medications were more likely to be prescribed a drug in violation of a black box warning than were young non-white men who took fewer medications. Patients at community health centers and hospital clinics were more often prescribed drugs in violation of such warnings than those treated at community-based private practices.


Interestingly, seven medications (carbamazepine, azathioprine, lithium carbonate or citrate, metformin, propoxyphene, valproate, and triamterene; 10.1% of all drugs) accounted for nearly three-quarters of all neglected warnings, and fewer than 1% of patients were found to have experienced adverse drug events attributable to failure to adhere to information provided in a black box warning.


The findings refute the researchers' hypothesis that health care practitioners often prescribe drugs without adhering to black box warnings, resulting in significant harm to patients, but the researchers call for the use of alerts in electronic records to notify prescribers that a medication bears such a warning and to render it more explicit.


For more information on black box warnings-and changes that are being made to them-see Practice Errors, page 77.-JC


Lasser KE, et al. Arch Intern Med 2006;166(3):338-44.



According to this study:


* 56% reduction in the rate of pulmonary exacerbations.


* Surprisingly, patients in placebo group manifest increased airway clearance.



Two recently published studies, one conducted in Australia and one in the United States, found that the use of hypertonic saline solution in patients with cystic fibrosis is associated with lower rates of exacerbations and enhanced mucus clearance.


The Australian study was a randomized, controlled trial involving 164 patients six years of age or older with cystic fibrosis. Those in the intervention group inhaled a 7% hypertonic saline solution twice daily for 48 weeks, while the ones in the control group inhaled 0.9% saline solution (also twice daily for 48 weeks). The patients were evaluated upon study enrollment and at regular follow-up visits; they completed quality-of-life questionnaires and underwent diagnostic tests such as spirometry and sputum analysis. The study's primary end point was the linear rate of change in lung function from baseline; secondary end points included quality-of-life measures and pulmonary exacerbation. The most significant result was a 56% reduction in the rate of pulmonary exacerbations in the intervention arm. No disease exacerbation was found among 76% of patients in the hypertonic saline group over the course of the study, compared with 62% in the control group, and when exacerbations did occur, there was a median of 11 days of antibiotic use in the hypertonic saline group, compared with 50 days in the control group.


In the smaller, 24-patient, U.S. study, researchers investigated whether pretreatment with amiloride would benefit patients with cystic fibrosis who were receiving a hypertonic 7% sodium chloride aerosol. The researchers sought to test the hypothesis that the use of amiloride (a sodium channel blocker) to delay the absorption of sodium would cause the hypertonic saline solution to increase the volume of surface liquid in the respiratory tract, promoting mucus clearance and improving lung function. The patients, who were 14 years of age or older, were randomly assigned to receive either the pretreatment (n = 12) or a placebo (a preparation masked for taste; n = 12) four times daily. The treatment period was 28 days, the first 14 of which constituted a baseline observation period. Assessments of the patients were made during the observation period and at three subsequent points (the 15th, 26th, and 28th days).


Surprisingly, it was the patients in the placebo group who manifested increases in one-hour clearance rates that persisted for longer than eight hours and increases in 24-hour mucus-clearance rates from baseline. In addition, although the absolute percentage changes in lung function were similar in the two groups over the study period, "comparisons of changes . . . revealed significant improvements in" forced vital capacity (FVC), forced expiratory volume at one second, and forced expiratory flow between 25% and 75% of FVC in the placebo group but not the group receiving amiloride.


Although the researchers' hypothesis is refuted by the trial results, the results still highlight the favorable effects of the administration of inhalation hypertonic saline solution. The trials demonstrate that the administration of hypertonic saline solution alone can enhance current cystic fibrosis treatment and that may improve the quality of the lives of patients with the disorder.-AK


Elkins MR, et al. N Engl J Med 2006;354(3):299-40; Donaldson SH, et al. N Engl J Med 2006;354(3):241-50.