One-quarter of patients with gout receive colchicine despite potential interactions
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Key takeaways:
- More than 25% of patients with gout who use colchicine prophylaxis were on potentially interacting medications.
- Serious adverse events were low, though women and older adults demonstrated more GI.
Approximately 26% of patients with gout are commonly prescribed colchicine prophylaxis despite already using medications with potential interactions, according to data published in Rheumatology.
“Colchicine toxicity is theoretically increased by concomitant treatment with common drugs,” Ram Bajpai, MS, PhD, of the Keele University School of Medicine, in the United Kingdom, and colleagues wrote. “Although colchicine is contraindicated in patients taking these medications, in our clinical experience from primary and secondary care, their co-prescription still commonly occurs. However, evidence that these factors are prognostic for adverse events is largely anecdotal or theoretical, and large research studies are lacking.”
To examine how co-prescriptions with colchicine impact risk for adverse events in gout, Bajpai and colleagues conducted a retrospective cohort study. Using the linked U.K. Clinical Practice Research Datalink and Hospital Episode Statistics data sets, the researchers examined 13,945 adults with gout (mean age, 63.9 years) who initiated allopurinol with colchicine prophylaxis between April 1997 and November 2016.
Follow-up lasted for 6 months or until end of colchicine treatment. The researchers calculated the proportion of patients prescribed potentially interacting drugs — defined as statins, fibrates, verapamil, diltiazem, digoxin, amiodarone, oral ketoconazole and macrolide antibiotics — in the 30 days before index. They also estimated the risk for adverse events, including diarrhea, nausea or vomiting, myocardial infarction, neuropathy, myalgia, myopathy, rhabdomyolysis and bone marrow suppression.
Overall, 26% (95% CI, 25%-27%) of patients were prescribed at least one potentially interacting medication, according to the researchers. The most frequent were statins (21%; 95% CI, .2-.22), followed by digoxin, diltiazem and macrolide antibiotics. Statins were not linked to increased adverse events, except atorvastatin, which was linked with myocardial infarction (HR = 2.21; 95% CI, 1.14-4.27).
Patterns of adverse events included “generally higher” diarrhea, nausea and vomiting among women and older adults, as well as more myocardial infarctions at older ages, the researchers wrote. Per 10,000 person-years, the most common adverse events were diarrhea with fibrate prescription (4,322.8; 95% CI, 2,161.8-8,664), myalgia with verapamil prescription (2,873.7; 95% CI, 404.8-20,000) and diarrhea with macrolide antibiotics (2,855.3; 95% CI, 1,361.2-5,989.3).
“We found that people were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine,” Bajpai and colleagues wrote. “Adverse events were more common in people who were older, had more comorbidities and were prescribed certain potentially interacting medications.
“Reassuringly, the rate of serious adverse events was low, providing reassurance for people with gout and for clinicians,” they added. “We also found no evidence that the prescription of statins significantly increased the risk of adverse events except atorvastatin being associated with MI.
“Reassuringly, the rate of serious adverse events was low,” Bajpai and colleagues wrote. “We also found no evidence that the prescription of statins significantly increased the risk of adverse events except atorvastatin being associated with MI. ... Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions when initiating allopurinol, directly benefiting people with gout and their clinicians.”
Perspective
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J. Nicholas Manwaring, MSN, APRN, FNP-C
A few of the strong points of this study were that it involved a large sample size over a long period of time — almost 14,000 people over 20 consecutive years. It also looked at multiple potential adverse effects of colchicine, namely concomitant drug interaction.
Colchicine toxicity is known to be associated with chronic kidney disease. It was interesting to note that the drug interaction between statin use and colchicine was less than predicted. Many of the patients in the study were on statin therapy concurrently with colchicine prophylaxis. Although atorvastatin was associated with myocardial infarction, it was surprising that concurrent use of other statin medications and colchicine did not significantly increase the risk for adverse events, as would be suspected given their relative contraindication.
Adverse events in the study were identified according to documented diagnostic codes. It was possible that the adverse event of diarrhea with the use of colchicine was not adequately identified given that it may not have been reported by the patient to the clinician, since it is not necessarily a severe effect, and as a result could go underreported compared with more severe adverse effects such as MI, myelosuppression and rhabdomyolysis.
Another potential weaker area of the study was that there were disproportionately more males than females in the sample size — 78% vs 22%.
From my experience, it can sometimes be difficult to definitively diagnose gout. The only absolute diagnostic criterion for gout is the presence of urate crystals on a joint aspiration. This can be difficult to obtain particularly when a patient is not able to be seen urgently at the time of gout flare. Often, by the time the patient comes to clinic, the attack has resolved or the active gouty joint has been swollen for so long the crystals have settled and do not present on aspiration. Serum uric acid levels can also be normal during an acute gout attack.
Palindromic rheumatism is a rare early manifestation of rheumatoid arthritis that can mimic the rapid onset, and rapid resolution, manifestations of an acute gout attack. Psoriatic arthritis can also sometimes present like a gout attack with its dactylitis.
I have found colchicine to be helpful as a confirmatory diagnostic tool in such cases, as it tends to work rather rapidly to abate an acute gout attack and will not affect rheumatoid arthritis or psoriatic arthritis symptoms.
Although careful monitoring of patients on medications with the potential for drug interactions is warranted, this study offers some reassurance in the use of colchicine for patients who are on medications with potential interactions, particularly when other options such as NSAIDs and systemic steroids are of greater risk.
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