Severe soft-tissue injury following intravenous infusion of phenytoin. Patient and drug administration risk factors.

From April 8, 1982, through June 1984, 11 patients in a single hospital experienced 17 episodes of limb edema and discoloration after the intravenous (IV) administration of phenytoin sodium (Dilantin). One patient required a below-the-elbow amputation; all other patients recovered. No single drug lot was implicated. A case-control study was performed using three controls for each case; controls received IV infusions of phenytoin and were hospitalized close in time to the case patients. Compared with controls, patients with reactions were more often female and elderly and had underlying cardiovascular disease. Affected patients also received phenytoin through an IV catheter smaller than 20 gauge (50% vs 6%), at a rate greater than 25 mg/min (63% vs 19%), and in two or more IV infusions of phenytoin given "IV push" at the same site (81% vs 24%). High-risk patients require careful monitoring and stricter guidelines for the IV administration of phenytoin.

Trends in cost containment: where do we cut?

The current emphasis on cost containment and its impact on pharmacy practice is reviewed. Methods by which existing standards of practice can be maintained are presented. Strategies for increasing the pharmacist's role in patient care within this climate are discussed. Examples of cost-effective approaches to pharmacy management and practice are outlined. Specific approaches include fiscal management of inventory, efficient use of personnel, and developing programs that reduce health-care cost.

Adverse drug reaction reporting system: developing a well-monitored program.

The spontaneous reporting of adverse drug reactions (ADRs) at the St. John's Hospital and Memorial Medical Center was well below that reported in the literature. After review of procedures for reporting of ADRs at these institutions, the authors developed a system that was approved by their joint P & T Committee. The ADR reporting program developed uses concurrent monitoring of most hospital inpatients and a retrospective review of all emergency room patients. In the year after program implementation, 162 ADR reports were documented. From this program, a group of serious ADRs to one agent was identified and reported, both to the Food and Drug Administration and to the manufacturer. A well-developed ADR monitoring program may lead to heightened physician and nurse awareness and early problem identification, possibly decreasing morbidity for hospitalized patients.

Particulate matter in four reconstituted cephalosporin injections.

The amount and size of particulate contamination in three commercially available cephalosporin injections and a new product, anophilized cephalothin sodium injection, were studied. Particles in reconstituted cephalothin sodium (commercially available and anophilized), cephapirin sodium, and cephradine injections were counted using two methods: (1) modified USP membrane-filtration technique and (2) Elzone computerized particle analyzer. The amount of particulate contamination in the ranges of 10-24 and greater than or equal to 25 microns was determined by both methods. In the 10-24-microns range, the cephalothin, cephapirin, and cephradine products had significantly greater particle counts than the anophilized cephalothin product. The greater than or equal to 25-microns particle counts showed that the cephapirin and cephradine products had particle counts greater than the anophilized cephalothin product, while total particle counts showed the same results as the 10-24-microns particle counts. A comparison of counting methods showed that the only significant difference between the number of particulates obtained using the modified USP and Elzone computer methods was with the cephalothin product. Anophilized cephalothin sodium injection has significantly fewer particles in the size ranges studied. No conclusion could be reached as to the more accurate method for counting particles.

Establishing a fee for handling investigational drug studies.

The administrative aspects of a pharmacy coordinated investigational drug service and its related costs are described. The policies and procedures for administering investigational drug studies were reviewed and divided into tasks. The staff involved were interviewed to determine the time they spent performing each task. The space for storage of the investigational drugs was measured. The personnel and storage costs were calculated. An average of five hours is required to coordinate pharmacy participation in a drug study. A drug information specialist spends about 1.5 hours/study developing a data sheet on the investigational drug. Record keeping time is approximately 11 hours/study. The total annual personnel cost is +177/study. The space for storing the drugs costs +15.50/year/study. The pharmacy department charges a fee of +200/year for its involvement in investigational drug studies. This does not include dispensing fees, which are charged to the patient. At this hospital, the revenue generated can support a pharmacist half-time or a technician full-time.

Tobramycin-furosemide interaction.

A 70-year-old, 75-kg white female with a history of congestive heart failure was admitted with a two-week episode of progressive shortness of breath, increased abdominal distension, and ankle edema. Sputum Gram stains revealed gram-negative bacilli, and the patient was started on a loading dose of tobramycin 150 mg (2 mg/kg) over 30 minutes. The peak tobramycin level was 3.7 micrograms/ml drawn 45 minutes after the infusion was completed. Seven hours after the loading dose infusion, a trough level of 1.5 micrograms/ml was obtained. Based on the Sawchuk-Zaske method, the patient was started on a regimen of tobramycin 180 mg iv q8h. The following day, the patient received furosemide 120 mg iv. The trough and peak levels drawn 30 minutes before and after the fourth dose of tobramycin were 5.3 micrograms/ml and 16.2 micrograms/ml, respectively. The half-life of tobramycin remained relatively constant, while the volume of distribution decreased 40 percent after the administration of furosemide. This case illustrates that moderate doses of furosemide, administered to edematous patients receiving tobramycin, may cause an increase in both peak and trough levels, thus increasing the chances of ototoxicity and nephrotoxicity.