Colchicine

What it is

Colchicine is a plant alkaloid, originally from autumn crocus (Colchicum autumnale), now made and sold as tablets and capsules. It binds beta-tubulin and stops microtubules assembling, which prevents white cells - particularly neutrophils - from activating, releasing their granules and migrating to a site of inflammation. It also appears to interfere with assembly of the NLRP3 inflammasome and so with interleukin-1 beta release. It is a substrate of both CYP3A4 and the P-glycoprotein efflux pump, which is why drug and food interactions matter so much, and it has a narrow margin between a useful dose and a toxic one.

What the research says

Colchicine blunts the inflammatory response rather than killing anything or lowering uric acid. In acute gout the Cochrane review found low-quality evidence that a low dose helps more than placebo, with benefits similar to NSAIDs. In acute pericarditis a randomised trial halved recurrence with a number needed to treat of 4. In coronary disease the picture is genuinely unsettled: two trials found fewer cardiovascular events, and a third and larger trial found none at all. Its serious harms are concentrated in overdose and in interactions - fatal toxicity at ordinary doses has been reported when it is combined with drugs or grapefruit juice that block its clearance.

Evidence grade: Disputed.

How it works

Drug class: Anti-inflammatory alkaloid; tubulin polymerisation inhibitor (antimitotic, anti-gout agent)

Colchicine binds to beta-tubulin and stops microtubules forming. Neutrophils need an intact microtubule skeleton to activate, dump their granules and crawl towards inflamed tissue, so colchicine blocks the cellular machinery of an inflammatory flare. It also appears to interfere with assembly of the inflammasome complex in neutrophils and monocytes that switches on interleukin-1 beta. (Source 1)

What it is used for

• Cochrane found low-quality evidence that low-dose colchicine beats placebo: 418 per 1000 reported treatment success at 32 to 36 hours against 172 per 1000 on placebo, an absolute 25% improvement, with confidence intervals wide enough to include both an important and an unimportant benefit, and benefits similar to NSAIDs. Evidence: limited. (Source 2)
• The approval rests on two randomised trials in people starting urate-lowering therapy, which the label says decreased flare frequency; the label does not report effect sizes for them. Evidence: limited. (Source 3)
• Approval rests on three small placebo-controlled crossover studies totalling 48 adults. In one, 10 completers had 5 attacks in 90 days on colchicine against 59 on placebo; in another, 13 completers had 18 attacks in 60 days against 68 on placebo. Evidence: limited. (Source 4)
• Approved in the United States as Lodoco 0.5 mg on the strength of LoDoCo2 (6.8% vs 9.6%, HR 0.69, number needed to treat 36) and COLCOT (5.5% vs 7.1%, HR 0.77). The later and larger CLEAR SYNERGY trial in 7,062 people found no effect at all (9.1% vs 9.3%, HR 0.99) despite lowering C-reactive protein. Evidence: disputed. (Source 5)
• Not an FDA-approved indication in the United States. In the 240-patient ICAP trial, incessant or recurrent pericarditis occurred in 16.7% on colchicine versus 37.5% on placebo, number needed to treat 4, P<0.001, with no excess of adverse effects. Evidence: established. (Source 6)
• In the 11,340-patient RECOVERY randomisation, colchicine made no difference to 28-day mortality (21% vs 21%, rate ratio 1.01), time to discharge or progression to ventilation or death. Evidence: not-supported. (Source 7)

Interactions

• Grapefruit and grapefruit juice (label): Grapefruit blocks CYP3A4, the enzyme that clears colchicine, so colchicine builds up and the risk of toxicity rises. Both the gout label and the Lodoco label tell patients to avoid it. (Source 8)
• Clarithromycin and other strong CYP3A4 inhibitors (including itraconazole, ketoconazole, ritonavir and other protease inhibitors) (case reports): These stop colchicine being cleared, so levels climb. Fatal colchicine toxicity has happened at ordinary therapeutic doses with this combination, particularly in people with kidney impairment. The label makes the combination contraindicated in renal or hepatic impairment. (Source 9)
• Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) (case reports): Adding either drug to a stable regimen of the other has caused myopathy and rhabdomyolysis, including a fatality. The label warns that checking creatine kinase will not necessarily catch it in time. (Source 10)
• Fibrates and gemfibrozil (label): Other lipid-lowering drugs carry the same myopathy risk as statins when combined with colchicine. (Source 10)
• Ciclosporin (cyclosporine) and other P-glycoprotein inhibitors such as ranolazine (label): Colchicine is pumped out of cells by P-glycoprotein; blocking that pump raises colchicine levels. With Lodoco the combination with strong P-gp inhibitors is contraindicated. (Source 8)
• Digoxin (case reports): Digoxin is also a P-glycoprotein substrate and rhabdomyolysis has been reported with the combination. (Source 10)
• Herbal products and over-the-counter medicines generally (label): The label asks patients to report herbal products and non-prescription medicines before starting anything new, because interactions with colchicine can be fatal. No individual supplement is named in the colchicine tablet label. (Source 11)
• Oral contraceptives (ethinyl estradiol and norethindrone) (pharmacokinetic study): Hormone concentrations were unaffected in a study in healthy women, but the Lodoco label records gastrointestinal adverse events with the combination and advises caution. (Source 8)
• Alcohol (label): Neither the colchicine tablet label nor the Lodoco label documents a specific interaction with alcohol. What the labels do say is that gastrointestinal symptoms are usually the first sign of colchicine toxicity, so new gut symptoms should be investigated rather than attributed to something else. (Source 12)

Stopping it

• Colchicine causes no tolerance, misuse or dependence as far as the published record goes, so there is no withdrawal syndrome to taper around. (Source 13)
• Where colchicine has caused nerve or muscle toxicity, stopping it is the treatment, and symptoms generally resolve within one week to several months. (Source 14)
• Gastrointestinal symptoms are usually the earliest sign of colchicine building up to toxic levels, and the label says new symptoms should prompt evaluation for toxicity rather than being waited out. (Source 12)
• In acute colchicine poisoning there is no antidote and dialysis does not remove the drug, so stopping exposure and supportive care are all that is available. (Source 15)

What goes wrong

High-dose colchicine gave no more benefit than low-dose but caused far more adverse events, and low-dose colchicine was no better than NSAIDs. (Source 16)

• Systematic review, Low certainty.
• Size: 124 participants across two trials for the high-dose versus placebo comparison; 399 participants for the NSAID comparison.
• Who: Adults with an acute gout flare.
• How long: Outcomes at 32 to 36 hours and 7 days; adverse events to 4 weeks.
• Result: High-dose vs placebo: treatment success 518 per 1000 vs 240 per 1000, RR 2.16, 95% CI 1.28 to 3.65, absolute improvement 28%; adverse events 829 per 1000 vs 260 per 1000, RR 3.21, 95% CI 2.01 to 5.11, absolute difference 57% (26% more to 74% more). High-dose versus low-dose: little or no difference in treatment success but more adverse events. Low-dose versus NSAIDs: little or no benefit in treatment success or pain reduction at 7 days.
• Funding: not stated (Cochrane review)

but more adverse events were reported with high-dose colchicine (829 per 1000 compared with 260 per 1000): RR 3.21, 95% CI 2.01 to 5.11, absolute difference 57% (26% more to 74% more). Pain and function were not reported. Low-quality evidence from a single trial comparing high-dose to low-dose colchicine indicates there may be little or no difference in benefit in terms of treatment success at 32 to 36 hours but more adverse events associated with the higher dose.

Gastrointestinal side effects are the main dose-limiting harm of colchicine in gout, and they rise steeply with dose. (Source 17)

• Official position, Moderate certainty.
• Size: 185 participants (52 high dose, 74 low dose, 59 placebo)
• Who: Adults with a gout flare.
• How long: Up to 72 hours.
• Result: Gastrointestinal adverse reactions 26% on the recommended 1.8 mg over one hour, 77% on a non-recommended 4.8 mg over six hours, and 20% on placebo. Diarrhoea 23% low dose vs 77% high dose vs 14% placebo. Severe diarrhoea 19% and vomiting 17% on high dose, neither occurring on the recommended low dose.
• Funding: not applicable (FDA-approved labelling)

gastrointestinal adverse reactions occurred in 26% of patients using the recommended dose (1.8 mg over one hour) of colchicine compared to 77% of patients taking a non-recommended high dose (4.8 mg over six hours) of colchicine and 20% of patients taking placebo. Diarrhea was the most commonly reported drug-related gastrointestinal adverse event. As shown in Table 3, diarrhea is associated with colchicine treatment. Diarrhea was more likely to occur in patients taking the high-dose regimen than the low-dose regimen. Severe diarrhea occurred in 19% and vomiting occurred in 17% of patients taking the non-recommended high-dose colchicine regimen but did not occur in the recommended low-dose colchicine regimen.

In the same trial, serious pneumonia was significantly more common with colchicine. (Source 18)

• Randomized trial, Moderate certainty.
• Size: 4,745 participants.
• Who: Adults within 30 days of a myocardial infarction.
• How long: Median 22.6 months.
• Result: Pneumonia reported as a serious adverse event in 0.9% on colchicine vs 0.4% on placebo (P = 0.03). Diarrhoea 9.7% vs 8.9% (P = 0.35, not significant).
• Funding: independent public funding.

Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03)

In a retrospective review of hospital records in which groups were defined by whether the two drugs overlapped rather than by who died, prescribing clarithromycin and colchicine together was associated with death in about one in ten patients, with pre-existing kidney impairment the strongest risk factor. (Source 19)

• Cohort study, Very low certainty.
• Size: 116 patients (88 concomitant, 28 sequential)
• Who: Hospital inpatients prescribed both clarithromycin and colchicine during the same admission, largely elderly; groups were defined by exposure (88 given the drugs concomitantly, 28 sequentially), not by outcome.
• How long: Single hospital admission.
• Result: Death in 9 (10.2%) of 88 given the drugs concomitantly vs 1 (3.6%) of 28 given them sequentially. In multivariate analysis of the 88, longer overlapped therapy relative risk 2.16 (95% CI 1.41-3.31, P<=.01), baseline renal impairment RR 9.1 (1.75-47.06, P<.001) and development of pancytopenia RR 23.4 (4.48-122.7, P<.001) were independently associated with death.
• Funding: not stated.

Limit of this finding: This was a retrospective look back at hospital records, not a trial, and the two groups were not randomised, so the people given the drugs together may have differed from those given them one after the other in ways that also affected survival. The paper calls itself a retrospective study and describes its comparisons as case-control, but its groups were defined by which drugs patients received and death was the outcome measured, which makes it a retrospective cohort comparison rather than a true case-control study.

Nine (10.2%) of the 88 patients who received the 2 drugs concomitantly died. Only 1 (3.6%) of the 28 patients who received the drugs sequentially died. Multivariate analysis of the 88 patients who received concomitant therapy showed that longer overlapped therapy (relative risk [RR], 2.16; 95% confidence interval [CI], 1.41-3.31; P< or =.01), the presence of baseline renal impairment (RR, 9.1; 95% CI, 1.75-47.06; P<.001), and the development of pancytopenia (RR, 23.4; 95% CI, 4.48-122.7; P<.001) were independently associated with death.

Colchicine has a narrow therapeutic index, and ingestions above about 0.5 mg per kg carry a high death rate; the lowest reported lethal oral doses are 7 to 26 mg. (Source 20)

• Systematic review, Low certainty.
• Size: not stated as a participant count; a systematic review of MEDLINE 1966 to January 2010.
• Who: People with colchicine poisoning, intentional and unintentional.
• How long: Acute poisoning, with phases over 1 to 7 days.
• Result: Usual adult oral doses 1.2-2.4 mg/day for familial Mediterranean fever, 1.2 mg/day in acute gout and 0.5-0.6 mg/day three to four times a week for gout prophylaxis. High fatality rate above 0.5 mg/kg. Lowest reported lethal oral doses 7-26 mg.
• Funding: not stated.

High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.

In a review of 150 colchicine overdoses, mortality was 100% above 0.8 mg per kg, and fatalities have followed doses as low as 7 mg spread over four days. (Source 15)

• Official position, Moderate certainty.
• Size: 150 patients in the overdose review cited by the label.
• Who: People who overdosed on colchicine.
• How long: Toxicity in two stages over 24 to 72 hours.
• Result: Less than 0.5 mg/kg: survival with milder toxicities such as gastrointestinal symptoms. 0.5 to 0.8 mg/kg: more severe reactions such as myelosuppression. More than 0.8 mg/kg: 100% mortality. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients survived more than 60 mg.
• Funding: not applicable (FDA-approved labelling)

Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg.

Colchicine at ordinary therapeutic doses can suppress the bone marrow and cause nerve and muscle toxicity, including rhabdomyolysis, with kidney impairment and old age the main risk factors. (Source 14)

• Official position, Moderate certainty.
• Size: not quantified in the label.
• Who: People on long-term therapeutic doses, especially with renal dysfunction or advanced age.
• How long: chronic treatment.
• Result: No rate is given. Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anaemia have been reported at therapeutic doses. Symptoms of neuromuscular toxicity generally resolve within 1 week to several months after colchicine is stopped.
• Funding: not applicable (FDA-approved labelling)

Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid or benzafibrate (themselves associated with myotoxicity) or cyclosporine with colchicine may potentiate the development of myopathy [see Drug Interactions (7)]. Once colchicine is stopped, the symptoms generally resolve within one week to several months.

At the cardiovascular dose of 0.5 mg daily, muscle pain was slightly but significantly more common than with placebo. (Source 21)

• Official position, Moderate certainty.
• Size: 5,522 participants in LoDoCo2.
• Who: Adults with chronic coronary disease.
• How long: Median 28.6 months.
• Result: Myalgia reported for 21.2% on colchicine vs 18.5% on matching placebo; hazard ratio 1.15, 95% CI 1.01-1.31.
• Funding: not applicable (regulatory position summarising LoDoCo2)

In the LoDoCo2 trial, myalgia was reported for 21.2% of individuals randomized to colchicine and 18.5% of individuals randomized to matching placebo (hazard ratio 1.15, 95%CI 1.01-1.31).

What the evidence supports

Low-dose colchicine may help an acute gout flare more than placebo, but the evidence is low quality and the confidence interval spans important and unimportant benefit. (Source 2)

• Systematic review, Low certainty.
• Size: 103 participants in the single trial contributing to the primary comparison, within a review of 4 trials and 803 randomised participants.
• Who: Adults with an acute gout flare, mean age across trials 51.2 to 70 years.
• How long: Outcome at 32 to 36 hours; trial durations 48 hours to 12 weeks.
• Result: Treatment success (50% or greater pain reduction) 418 per 1000 on low-dose colchicine vs 172 per 1000 on placebo; risk ratio 2.43, 95% CI 1.05 to 5.64; absolute improvement 25% more reported success (7% more to 42% more). Total adverse events 364 per 1000 vs 276 per 1000; RR 1.32, 95% CI 0.68 to 2.56. No participants withdrew due to adverse events or reported any serious adverse events. Pain, inflammation and function were not reported.
• Funding: not stated (Cochrane review)

Limit of this finding: One trial of 103 people carries this result, and the review rates it low-quality. Its own confidence interval runs from a benefit too small to matter to a large one, so the size of the benefit is not settled. The review also records that pain, inflammation and joint function were not reported at all in that trial. The sentence is printed in the review with an opening bracket that is never closed, which is the source's punctuation, not a cut.

The number of people who reported treatment success (50% or greater pain reduction) at 32 to 36 hours was slightly larger with low-dose colchicine (418 per 1000) compared with placebo (172 per 1000; risk ratio (RR) 2.43, 95% confidence interval (CI) 1.05 to 5.64; absolute improvement 25% more reported success (7% more to 42% more, the 95% CIs include both a clinically important and unimportant benefit); relative change of 143% more people reported treatment success (5% more to 464% more).

In the pivotal gout-flare trial, the low-dose regimen produced about the same response rate as a dose nearly three times larger, while causing a third as many gastrointestinal adverse events. (Source 3)

• Official position, Moderate certainty.
• Size: 184 participants (74 low-dose, 52 high-dose, 58-59 placebo)
• Who: Adults meeting American College of Rheumatology criteria for gout, treated within 12 hours of flare onset.
• How long: 24 hours for the primary endpoint; 72 hours of diary recording.
• Result: Responders 28 of 74 (38%) on low dose (1.8 mg total) and 17 of 52 (33%) on high dose (4.8 mg total) versus 9 of 58 (16%) on placebo; difference versus placebo 22 percentage points (95% CI 8 to 37) for low dose and 17 (95% CI 1 to 33) for high dose.
• Funding: not applicable (FDA-approved labelling summarising the published trial)

Rates of response were similar for the recommended low-dose treatment group (38%) and the non-recommended high-dose group (33%) but were higher as compared to the placebo group (16%) as shown in Table 8.

In 4,745 people within 30 days of a heart attack, colchicine 0.5 mg daily reduced a composite of ischaemic cardiovascular events. (Source 18)

• Randomized trial, Moderate certainty.
• Size: 4,745 participants (2,366 colchicine, 2,379 placebo)
• Who: Adults recruited within 30 days after a myocardial infarction.
• How long: Median 22.6 months.
• Result: Primary endpoint 5.5% vs 7.1%; hazard ratio 0.77, 95% CI 0.61 to 0.96, P = 0.02, an absolute difference of 1.6 percentage points. Component hazard ratios: cardiovascular death 0.84 (0.46 to 1.52), resuscitated cardiac arrest 0.83 (0.25 to 2.73), myocardial infarction 0.91 (0.68 to 1.21), stroke 0.26 (0.10 to 0.70), urgent hospitalisation for angina leading to revascularisation 0.50 (0.31 to 0.81).
• Funding: independent public funding (Government of Quebec and others)

The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization.

The FDA label for the cardiovascular indication puts the absolute benefit at a number needed to treat of 36 over a median of 28.6 months. (Source 22)

• Official position, Moderate certainty.
• Size: 5,522 participants.
• Who: Adults with stable coronary artery disease.
• How long: Median time on study medication 28.6 months.
• Result: 31% lower relative risk of the primary composite endpoint (HR 0.69; 95% CI 0.57 to 0.83; p<0.001) and a number needed to treat of 36.
• Funding: not applicable (regulatory position; Lodoco SPL version 4, effective 13 August 2026)

In the LoDoCo2 trial, 0.5 mg of colchicine once daily resulted in a 31% lower relative risk (RRR) of the primary composite endpoint events compared to placebo (HR, 0.69; 95% [CI] 0.57 to 0.83; p<0.001) and the number needed to treat (NNT) was 36.

In acute pericarditis, adding colchicine to aspirin or ibuprofen halved the rate of persistent or recurrent disease, with a number needed to treat of 4. (Source 6)

• Randomized trial, Moderate certainty.
• Size: 240 participants (120 per group)
• Who: Adults with a first attack of acute pericarditis, all also receiving aspirin or ibuprofen.
• How long: 3 months of colchicine; outcomes to recurrence.
• Result: Incessant or recurrent pericarditis 20 (16.7%) vs 45 (37.5%); relative risk reduction 0.56, 95% CI 0.30 to 0.72; number needed to treat 4; P<0.001. Symptom persistence at 72 hours 19.2% vs 40.0% (P=0.001); recurrences per patient 0.21 vs 0.52 (P=0.001); hospitalisation 5.0% vs 14.2% (P=0.02); remission at 1 week 85.0% vs 58.3% (P<0.001). Overall adverse effects and discontinuation rates were similar and no serious adverse events were seen.
• Funding: not stated in full; funded by a local health authority (former Azienda Sanitaria Locale 3 of Turin) and Acarpia.

The primary outcome occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (relative risk reduction in the colchicine group, 0.56; 95% confidence interval, 0.30 to 0.72; number needed to treat, 4; P<0.001). Colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%, P=0.001), the number of recurrences per patient (0.21 vs. 0.52, P=0.001), and the hospitalization rate (5.0% vs. 14.2%, P=0.02). Colchicine also improved the remission rate at 1 week (85.0% vs. 58.3%, P<0.001). Overall adverse effects and rates of study-drug discontinuation were similar in the two study groups.

What the evidence does not support

The largest trial of colchicine after a heart attack, with 7,062 patients followed a median of three years, found no reduction in cardiovascular events despite a measurable fall in C-reactive protein. (Source 23)

• Randomized trial, High certainty.
• Size: 7,062 participants at 104 centres in 14 countries (3,528 colchicine, 3,534 placebo)
• Who: Adults who had had a myocardial infarction.
• How long: Median 3 years.
• Result: Primary outcome 322 of 3,528 (9.1%) vs 327 of 3,534 (9.3%); hazard ratio 0.99, 95% CI 0.85 to 1.16, P = 0.93. C-reactive protein least-squares mean difference at 3 months -1.28 mg per litre (95% CI -1.81 to -0.75). Diarrhoea 10.2% vs 6.6%, P<0.001, with no difference in serious infections.
• Funding: independent public funding (Canadian Institutes of Health Research and others)

A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups.

In people admitted to hospital with COVID-19, colchicine did not reduce death, length of stay or progression to ventilation. (Source 7)

• Randomized trial, High certainty.
• Size: 11,340 participants (5,610 colchicine, 5,730 usual care)
• Who: Adults admitted to hospital with suspected or confirmed SARS-CoV-2 infection at 181 hospitals in the UK, Indonesia and Nepal.
• How long: Up to 10 days of treatment; 28-day outcomes.
• Result: 28-day death 1,173 (21%) vs 1,190 (21%); rate ratio 1.01, 95% CI 0.93 to 1.10; p=0.77. Median time to discharge alive 10 days in both groups. Discharged alive within 28 days 70% vs 70%, rate ratio 0.98 (0.94 to 1.03), p=0.44. Invasive ventilation or death 25% vs 25%, risk ratio 1.02 (0.96 to 1.09), p=0.47.
• Funding: independent public and charitable funding (UK Research and Innovation, NIHR and Wellcome Trust)

Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77).

Colchicine does not cause tolerance, misuse or dependence as far as the literature records. (Source 13)

• Official position, Low certainty.
• Size: not applicable.
• Who: not applicable.
• How long: not applicable.
• Result: No cases recorded; the label states that tolerance, abuse and dependence have not been reported.
• Funding: not applicable (FDA-approved labelling)

Tolerance, abuse or dependence with colchicine has not been reported.

One of the three randomised trials the label cites for familial Mediterranean fever produced no usable result. (Source 4)

• Official position, Low certainty.
• Size: 11 patients enrolled, six of whom completed the study before it was stopped.
• Who: Patients with familial Mediterranean fever.
• How long: not stated; stopped at an interim analysis.
• Result: The label records that the third study was discontinued after an interim analysis of six of the 11 patients enrolled had completed it, and that the results could not be confirmed. It does not report a result for that study.
• Funding: not applicable (FDA-approved labelling)

The third study was discontinued after an interim analysis of six of the 11 patients enrolled had completed the study; results could not be confirmed.

Where the evidence is mixed

In 5,522 people with chronic coronary disease, colchicine 0.5 mg daily lowered cardiovascular events, but deaths from non-cardiovascular causes were numerically higher. (Source 5)

• Randomized trial, Moderate certainty.
• Size: 5,522 participants (2,762 colchicine, 2,760 placebo)
• Who: Adults aged 35 to 85 with proven coronary artery disease, clinically stable for at least 6 months; 15.3% female, mean age 66.
• How long: Median 28.6 months.
• Result: Primary endpoint 187 (6.8%) vs 264 (9.6%); 2.5 vs 3.6 events per 100 person-years; hazard ratio 0.69, 95% CI 0.57 to 0.83, P<0.001. Key secondary 115 (4.2%) vs 157 (5.7%), HR 0.72 (0.57 to 0.92), P = 0.007. Death from non-cardiovascular causes 0.7 vs 0.5 events per 100 person-years, HR 1.51, 95% CI 0.99 to 2.31.
• Funding: independent public funding (National Health Medical Research Council of Australia and others)

The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).

Where the research disagrees

Whether low-dose colchicine reduces cardiovascular events after a heart attack

• Tardif and colleagues, NEJM 2019 (COLCOT), randomised, double-blind, placebo-controlled trial, 4,745 participants, median 22.6 months, publicly funded: The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). (Source 18)
• Jolly and colleagues, NEJM 2025 (CLEAR SYNERGY / OASIS 9), randomised, placebo-controlled 2-by-2 factorial trial, 7,062 participants at 104 centres in 14 countries, median 3 years, publicly funded: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Source 24)

How much confidence to place in colchicine for an acute gout flare

• McKenzie and colleagues, Cochrane 2021, Cochrane systematic review of 4 randomised trials, 803 participants, GRADE low quality for every comparison: We found low-quality evidence that low-dose colchicine may be an effective treatment for acute gout when compared to placebo and low-quality evidence that its benefits may be similar to NSAIDs. (Source 25)
• FDA-approved colchicine tablet labelling, regulatory position based on one randomised dose-comparison trial, SPL version 10 effective 20 August 2025: Colchicine tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare. (Source 26)

How much

• Reference intake: Colchicine is a prescription medicine and the dose is set by the prescriber. The FDA label for colchicine tablets (SPL version 10, effective 20 August 2025) gives 0.6 mg once or twice daily for gout flare prophylaxis, 1.2 mg at the first sign of a flare followed by 0.6 mg an hour later for treatment, and 1.2 mg to 2.4 mg daily for familial Mediterranean fever. The separate Lodoco label gives 0.5 mg once daily for cardiovascular risk reduction. (Source 27)
• Upper limit: There is no reference intake or tolerable upper intake level for a prescription drug. The label caps gout flare prophylaxis at 1.2 mg per day and gout flare treatment at 1.8 mg over a one-hour period, stating that higher doses have not been found more effective. For comparison, the poisoning literature puts a high fatality rate above 0.5 mg per kg and the label reports 100% mortality above 0.8 mg per kg. (Source 27)
• Studied: COLCOT gave 0.5 mg once daily for a median of 22.6 months to people within 30 days of a myocardial infarction. (Source 18)
• Studied: LoDoCo2 gave 0.5 mg once daily for a median of 28.6 months to people with chronic coronary disease. (Source 5)
• Studied: CLEAR SYNERGY randomised 7,062 post-infarction patients to colchicine or placebo for a median of 3 years. (Source 23)
• Studied: The pericarditis trial gave 0.5 mg twice daily for 3 months to people over 70 kg and 0.5 mg once daily to those 70 kg or under, on top of aspirin or ibuprofen. (Source 28)
• Studied: The gout flare trial compared a 1.8 mg total low-dose regimen with a 4.8 mg total high-dose regimen and placebo. (Source 3)
• Studied: RECOVERY gave 1 mg after randomisation then 0.5 mg 12 hours later and then 0.5 mg twice a day for up to 10 days (the trial report writes those doses as 500 micrograms), with the frequency halved for moderate CYP3A4 inhibitors, low kidney function or body weight under 70 kg. (Source 29)

A common belief, and what the research shows

The belief: Colchicine is an ancient herbal remedy for gout, so it must be gentle and safe.

What the research shows: Colchicine has one of the narrowest safety margins of any commonly prescribed drug. The poisoning review states: "High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg." The FDA label records that "There was 100% mortality in those who ingested more than 0.8 mg/kg." and that "Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period". Even at ordinary doses, "Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses.", and combining it with clarithromycin was followed by death in about one in ten hospital patients in a retrospective study.

Questions and answers

What is it?

Colchicine is an alkaloid from the autumn crocus, sold as a prescription tablet or capsule. It is an anti-inflammatory that works on the cell skeleton rather than on the immune signalling pathways most anti-inflammatories target. It does not lower uric acid and it is not a painkiller in the usual sense. (Source 1)

What does it do in the body?

It stops neutrophils and monocytes doing the things that drive an inflammatory flare: it blocks microtubule assembly so these cells cannot activate, release their granules or migrate into inflamed tissue, and it appears to interfere with the inflammasome complex that switches on interleukin-1 beta. That is why it works in gout, in familial Mediterranean fever and in pericarditis, which are all inflammasome-driven. (Source 1)

Is it good or bad for you?

Both, and the dose is the hinge. The recommended low dose for a gout flare helped about as often as a dose nearly three times larger while causing a third as many gut side effects; the high dose gave 829 adverse events per 1000 against 260 on placebo. In overdose colchicine is lethal: the label reports 100% mortality among people who swallowed more than 0.8 mg per kilogram of body weight, which is many times a day's prescribed dose, and those figures describe poisoning, not treatment. In coronary disease the benefit is genuinely disputed, with two positive trials and one larger null trial. (Source 17)

How do you get more of it?

Colchicine is prescription-only; it is not sold as a supplement and should not be obtained from the plant, which is lethally poisonous. The label sets out the doses: 0.6 mg once or twice daily for gout flare prophylaxis, 1.2 mg then 0.6 mg an hour later for a flare, 1.2 to 2.4 mg daily for familial Mediterranean fever, and separately 0.5 mg once daily for cardiovascular risk reduction. (Source 27)

If it is harmful, what reduces it?

If colchicine levels are too high, stopping the drug is the only route - dialysis does not remove it and there is no antidote in commercial use. Where neuromuscular toxicity has developed, symptoms generally settle within a week to several months after it is stopped. Avoiding grapefruit and CYP3A4 or P-glycoprotein inhibitors is what prevents levels building up in the first place. (Source 14)

Why might someone be low in it or missing it?

Someone may be on a lower dose or none because of kidney or liver impairment, because they take a strong CYP3A4 or P-glycoprotein inhibitor (which makes the combination contraindicated in renal or hepatic impairment), because of pre-existing blood problems, or because gut side effects forced them off it. The label requires dose reduction or interruption even in people with normal kidney and liver function when an interacting drug is needed. (Source 30)

Which whole foods contain it or feed it?

No food in ordinary use contains colchicine; the plant it comes from, autumn crocus, is poisonous and is not a food. The food that matters is the one to avoid: grapefruit and grapefruit juice raise colchicine exposure by blocking the enzyme that clears it, and both labels advise avoiding them. (Source 11)

What happens if you do not have it?

Colchicine is a medicine, not a nutrient, so there is no deficiency state. 'Without it' means the underlying condition runs its own course: in familial Mediterranean fever, the placebo arms of the small crossover trials had many more attacks - 59 attacks in 90 days against 5 on colchicine in one study, and 68 in 60 days against 18 in another. (Source 4)

How can you test for it?

There is no routine blood test for colchicine levels in ordinary care and no therapeutic range is defined in the label. What gets monitored is the consequences: full blood count for myelosuppression, kidney and liver function because both govern clearance, and muscle symptoms. The label warns explicitly that checking creatine kinase does not reliably catch severe myopathy before it happens. (Source 10)

References

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2. Cochrane Database of Systematic Reviews. Colchicine for acute gout.. 2021. PMID 34438469, DOI 10.1002/14651858.CD006190.pub3. Read the source
3. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 14 Clinical Studies. 2025. Read the source
4. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 14 Clinical Studies (FMF). 2025. Read the source
5. New England Journal of Medicine. Colchicine in Patients with Chronic Coronary Disease.. 2020. PMID 32865380, DOI 10.1056/NEJMoa2021372. Read the source
6. New England Journal of Medicine. A randomized trial of colchicine for acute pericarditis.. 2013. PMID 23992557, DOI 10.1056/NEJMoa1208536. Read the source
7. Lancet Respiratory Medicine. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.. 2021. PMID 34672950, DOI 10.1016/S2213-2600(21)00435-5. Read the source
8. DailyMed / U.S. National Library of Medicine. LODOCO (colchicine tablets 0.5 mg) - prescribing information, Section 7 Drug Interactions (Table 1, with its footnote). 2026. Read the source
9. Clinical Infectious Diseases. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study (Conclusions).. 2005. PMID 16007523, DOI 10.1086/431592. Read the source
10. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 7 Drug Interactions (Table 4). 2025. Read the source
11. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 17 Patient Counseling Information - Fatal Overdose, Blood Dyscrasias, Drug and Food Interactions. 2025. Read the source
12. DailyMed / U.S. National Library of Medicine. LODOCO (colchicine tablets 0.5 mg) - prescribing information, Section 5 Warnings and Precautions. 2026. Read the source
13. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 9 Drug Abuse and Dependence. 2025. Read the source
14. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 5.4 Neuromuscular Toxicity. 2025. Read the source
15. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 10 Overdosage. 2025. Read the source
16. Cochrane Database of Systematic Reviews. Colchicine for acute gout (high-dose comparison).. 2021. PMID 34438469, DOI 10.1002/14651858.CD006190.pub3. Read the source
17. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 6.1 Clinical Trials Experience in Gout. 2025. Read the source
18. New England Journal of Medicine. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction.. 2019. PMID 31733140, DOI 10.1056/NEJMoa1912388. Read the source
19. Clinical Infectious Diseases. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study (Results).. 2005. PMID 16007523, DOI 10.1086/431592. Read the source
20. Clinical Toxicology. Colchicine poisoning: the dark side of an ancient drug.. 2010. PMID 20586571, DOI 10.3109/15563650.2010.495348. Read the source
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22. DailyMed / U.S. National Library of Medicine. LODOCO (colchicine tablets 0.5 mg) - prescribing information, Section 14 Clinical Studies. 2026. Read the source
23. New England Journal of Medicine. Colchicine in Acute Myocardial Infarction.. 2025. PMID 39555823, DOI 10.1056/NEJMoa2405922. Read the source
24. New England Journal of Medicine. Colchicine in Acute Myocardial Infarction (Conclusions).. 2025. PMID 39555823, DOI 10.1056/NEJMoa2405922. Read the source
25. Cochrane Database of Systematic Reviews. Colchicine for acute gout (Authors' conclusions).. 2021. PMID 34438469, DOI 10.1002/14651858.CD006190.pub3. Read the source
26. DailyMed / U.S. National Library of Medicine (labeler: PAR Health USA, LLC). COLCHICINE tablet, film coated - prescribing information, Section 1 Indications and Usage with Section 1.1 Gout Flares, SPL version 10, effective 2025-08-20. 2025. Read the source
27. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 2.1 Gout Flares (dosage). 2025. Read the source
28. New England Journal of Medicine. A randomized trial of colchicine for acute pericarditis (Methods).. 2013. PMID 23992557, DOI 10.1056/NEJMoa1208536. Read the source
29. Lancet Respiratory Medicine. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): Methods.. 2021. PMID 34672950, DOI 10.1016/S2213-2600(21)00435-5. Read the source
30. DailyMed / U.S. National Library of Medicine. COLCHICINE tablet, film coated - prescribing information, Section 5.3 Drug Interactions. 2025. Read the source