Promoting the Safe Use of Intravenous Colchicines
Colchicine is an antimitotic that is effective in treating acute gout and other rheumatologic and nonrheumatologic conditions. Its toxicity greatly limits its utility, however; adverse events include gastrointestinal symptoms, electrolyte disturbances, changes in mental status, hypovolemia, and bone marrow suppression. The risk of toxicity with intravenous use depends on the total dose over a period of time, the presence of comorbid conditions, and the sizes of individual doses. In the United States, colchicine is a high-toxicity-alert medication according to the Institute for Safe Medication Practices (ISMP). ISMP recommends that safety measures include computer warnings, dosage caps, and criteria for use.

Experience with i.v. and oral colchicine at the University of Pittsburgh Medical Center (UPMC) has shown that adverse events may be moderate to severe—ranging from gastrointestinal upset to rare but severe bone marrow suppression leading to overwhelming infection and death. Although the use of i.v. colchicine at UPMC has been minimal, safety guidelines were developed because of the severity of some adverse events. The low therapeutic index, particularly in patients with renal or hepatic dysfunction or extrahepatic biliary obstruction, necessitates careful patient selection and dosage limits. The guideline development described here may serve as a template for using adverse-event and medication error data to develop practice guidelines for the safe use of other agents.

An extensive literature review was performed to investigate the toxicity associated with i.v. and oral colchicine. This included dosing strategies for patients with renal and hepatic dysfunction, that are considered special populations (appendix). A retrospective review was then performed for all hospitalized patients receiving colchicine. A computerized list of drugs (Cerner Millennium HNA, Kansas City, MO) was used to collect data both for admitted patients who were already receiving colchicine and those newly started on colchicine. From July 1, 2001, to August 30, 2002, three patients were prescribed i.v. colchicine, of whom two had adverse events ranging from transient bone marrow suppression to septic shock and death. This investigation of i.v. colchicine use at our hospital revealed that i.v. colchicine was rarely used but that, when it was used, the dosage was incorrect, resulting in adverse events. Pharmacists collaborated with physicians from rheumatology, internal medicine, and the continuing-education center to develop a set of strict safety guidelines regarding colchicine dosing, contraindications, and special populations at high risk for toxicity. Safe practice guidelines were developed and presented to the pharmacy and therapeutics (P&T) committee. The guidelines focused on rheumatology restriction of i.v. colchicine use and therapeutic interchange with oral colchicine in patients with compromised renal function. The guidelines were approved by the P&T committee in May 2003.

The guidelines were implemented by a combination of oral, written, and electronic mechanisms, including didactic educational sessions for both physicians and pharmacists, one-on-one sessions, educational packets, computerized order alerts for pharmacists, and computerized alerts that automatically sent a computerized continuing-medical-education session to physicians ordering i.v. colchicine.

A concurrent patient-monitoring program was designed to evaluate the impact of the guidelines. A computerized report identified patients receiving oral or i.v. colchicine. Patient drug therapy was evaluated for safety, and the data were recorded on a colchicine-monitoring form. The form included information on patient demographics, patient-specific drug and disease information, the indication for colchicine use, and dosage data.

Pharmacists' dosage-related interventions for patients prescribed colchicine were recorded in a database of medication errors and adverse events. These interventions, which occurred before harm could reach the patient, were categorized by type and cause of prescribing error. The safety guidelines led to five interventions, all involving prevention of i.v. colchicine use. In one case, a pharmacist prevented use for a patient with renal dysfunction. Rheumatology evaluated this patient and discontinued i.v. colchicine.