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VBCR - February 2015, Volume 4, No 1 - Gout
Rosemary Frei, MSc

Although colchicine has been used for centuries to treat gout, research on this drug is still revealing new treatment dimensions, according to a review article by Michael Pillinger, MD, and other clinician-researchers.1

Physicians can apply this new knowledge to help ensure their patients with gout and other rheumatic diseases are optimally treated, according to Pillinger, a professor in the Division of Rheumatology, NYU Hospital for Joint Diseases, New York. This includes providing the most appropriate starting dose and adjustments.

“Based on recent pharmacokinetic studies, colchicine use for acute gout is shown to be as effective at a dose of 1.2 mg followed by 0.6 mg 1 hour later, as compared to the previously used regimen of 0.6 mg hourly, but with side effects equivalent to [those associated with] placebo,” Pillinger told Value-Based Care in Rheumatology in summarizing one of the key messages from the article.

He also noted that “colchicine dosing, whether acute or chronic, needs to be adjusted for renal function as well as the coadministration of moderate to strong CYP3A4 inhibitors and/or P-glycoprotein inhibitors such as a number of antiretrovirals and azole antifungals. Of particular concern is coadministration of clarithromycin, owing to the relatively common use of that agent.”

Colchicine was approved by the US Food and Drug Administration (FDA) in 2009 for acute gout and Mediterranean fever, and is considered to be first-line treatment for those conditions as well as for the prophylaxis of gout. The agent also is used for patients with pseudogout, pericarditis, Behcet disease, and neutrophilic dermatoses. Moreover, the medication now has been shown in clinical trials to help prevent or treat some cardiovascular diseases, noted Pillinger and his coauthors.

Colchicine is largely metabolized by CYP3A4 and P-glycoprotein in the liver. The pathways constitute the nexus of colchicine’s interactions with a number of other drugs, ranging from clarithromycin and fluoxetine to azole antifungals and nondihydropyridine calcium channel blockers, and from cyclosporine to a number of statins. Moreover, colchicine’s plasma concentration and hence toxicity risk increase significantly with age because of a reduction in total body clearance. For some older patients, starting with half the usual dose and titrating up as needed may be a reasonable strategy, according to Pillinger.

He and his colleagues note that the FDA originally included but later withdrew approval for intravenous colchicine because of the risk of lethal overdose—even at intravenous doses of 0.5 mg/kg, colchicine is very toxic.

The Acute Gout Flare Receiving Colchicine Evaluation (AGREE) trial indicated that 1.2 mg followed 1 hour later by 0.6 mg has similar efficacy and fewer adverse events compared with 1.2 mg followed by 0.6 mg every hour for 6 hours for a maximum of 4.8 mg.2 This led to the FDA’s approval of the lower dose for acute gout. The American College of Rheumatology echoes this recommendation.

In summary, colchicine is beneficial for:

  • Prophylaxis and acute treatment of calcium pyrophosphate crystal arthritis (pseudogout)
  • Familial Mediterranean fever— “Doses as high as 1.8 mg daily in divided doses are recommended, and even when colchicines does not adequately control the attacks it usually prevents the development of amyloid renal disease,” said Pillinger
  • Several types of vasculitis including Behcet disease
  • Neutrophilic dermatoses
  • Pericarditis including initial attacks of acute pericarditis.

According to the review article, there also is some evidence that colchicine may prevent or be used to treat stable coronary artery disease, acute coronary syndromes, and postoperative atrial fibrillation.

“Ongoing research will further elucidate the mechanism of action and therapeutic utility of this historic medicine,” concluded Pillinger and his coauthors.

References

  1. Slobodnick A, Shah B, Pillinger MH, et al. Colchicine: old and new [published online Dec 12, 2014]. Am J Med.
  2. Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62(4):1060-1068
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