to the editor: I read the article1 on the treatment of gout and hyperuricemia. I would like to comment that, in my experience of using colchicine to treat patients with gout, I have found nothing more effective than giving 2 mg of intravenous colchicine in a single dose. The toxicity from a single dose is very low, and it is now my treatment of choice for a patient with an acute gouty attack. I have quite a bit of experience using intravenous colchicine, and I have encountered some problems with extravasation causing some irritation; however, this is the only problem I have experienced.
I reviewed the article2 to which the authors referred to regarding the toxicity associated with the intravenous administration of colchicine. All of the patients described in the article who had toxic effects from intravenous colchicine administration had received large dosages over a short period. In fact, the recommendations at the end of the article indicate that “The IV administration of colchicine is an effective way of using the drug and, with appropriate precautions, should lead to little serious toxicity.”2
Guidelines provided in the article2 for the intravenous administration of colchicine include the following: (1) Single intravenous dosages should not exceed 2 to 3 mg, and cumulative total dosages for an attack should not be more than 4 to 5 mg; (2) Patients should not receive colchicine by any route of administration for seven days; (3) Colchicine dosages must be reduced in patients who have renal or hepatic disease and in older patients with apparently normal renal function; (4) Intravenous colchicine dosages should be half the size of oral dosages; (5) Absolute contraindications to intravenous colchicine therapy for patients with acute gout include combined renal and hepatic disease, creatinine clearance times below 10 mL per minute and extrahepatic biliary obstruction.
I wrote this letter because I am concerned that, after reading this article, physicians who do not have experience with intravenous colchicine therapy might be frightened away from what I believe is a highly effective treatment for patients with acute gout.
in reply: We appreciate the comments offered by Dr. Stephan concerning the use of intravenous colchicine, and we agree that it is often highly effective therapy for the treatment of patients with acute gouty arthritis. Colchicine is one of the great veteran drugs in medicine, with a long venerable history in the treatment of patients with gout. However, the potential toxicity of the intravenous route of administration is often under-appreciated, and we argue against its routine use.
Colchicine was available well before the 1969 U.S. Food and Drug Administration act that required phase III toxicity trials. Data on toxicity and adverse reactions are based solely on passive surveillance; therefore, the true incidence of adverse reactions, especially with infrequently used medicine, is unknown. Toxicity includes tissue necrosis, bone marrow suppression, disseminated intravascular coagulation, renal failure, seizure, sepsis and death.
Over the past 50 years, more than 20 deaths have been attributed to the use of intravenous colchicine. In fact, it is no longer licensed for clinical use in Great Britain. We agree with Dr. Stephan that improper dosing and poor patient selection accounts for the vast majority of reported serious toxicity. However, with the availability of published guidelines,1 accurately detailed by Dr. Stephan, improper use and subsequent toxicity continues to be a problem.2 Guidelines on the safe use of intravenous colchicine are not widely disseminated in general medical or rheumatology textbooks.
Although the Wallace1 criteria are often quoted, several other guidelines are published in the medical literature.3 We agree with previous authors2,4 that the Wallace criteria should be expanded to preclude colchicine therapy in patients with baseline leukopenia. We are most concerned that patients frequently receive care from multiple physicians, as is the case in most teaching hospitals. In this setting, minimizing the total dose of intravenous colchicine, or avoiding concomitant oral and intravenous administration, have proved to be difficult errors to avoid. In a medical setting where patients receive their care from a single physician who is well versed on the toxicity of and various guidelines for the administration of intravenous colchicine, the drug may safely be used.
Intravenous colchicine continues to have the smallest risk-to-benefit ratio of all drugs used for the treatment of patients with acute gouty arthritis. Given the efficacy and low toxicity of alternative treatments, the lack of any prospective studies evaluating the safety or efficacy of intravenous colchicine therapy, and the lack of readily available and validated administration guidelines, we continue to recommend against the routine use of a potentially lethal medicine for use in patients with a nonfatal illness.