What is the purpose of administering colchicine (nonsteroidal anti-inflammatory medication)?

Why We Give Colchicine

Colchicine is administered primarily to treat and prevent inflammatory attacks in Familial Mediterranean Fever (FMF), to treat acute gout flares and prevent gout recurrences, and to manage acute and recurrent pericarditis. 1

Primary Indications

Familial Mediterranean Fever (FMF)

• Colchicine is the mainstay treatment for FMF and should be started as soon as a clinical diagnosis is made. 1
• The ultimate goal is to achieve complete control of unprovoked attacks and minimize subclinical inflammation between attacks. 1
• Treatment prevents the development of AA amyloidosis, a serious complication that develops from ongoing uncontrolled inflammation. 1
• In patients with established AA amyloidosis, the aim is to obtain complete and sustained control of biochemical inflammation, measured by serum amyloid A (SAA) or C-reactive protein (CRP). 1
• Colchicine should be continued during conception, pregnancy, and lactation without discontinuation. 1

Acute Gout Flares and Prevention

• Colchicine is a first-line agent for treating acute gout attacks, with recommended dosing of 1.2 mg at the first sign of flare followed by 0.6 mg one hour later (maximum 1.8 mg over one hour). 1, 2
• For prophylaxis of gout flares, the recommended dose is 0.6 mg once or twice daily (maximum 1.2 mg/day). 2
• Prophylactic colchicine is particularly beneficial when initiating uric acid-lowering therapy (allopurinol, febuxostat, pegloticase), as these medications can trigger gout flares by mobilizing urate from tissue deposits. 2
• Treatment provides 50% pain relief in approximately one in three patients (NNT = 3). 1

Pericarditis

• Colchicine halves the risk of recurrence in patients with acute and recurrent pericarditis (relative risk 0.50,95% CI 0.42-0.60). 3
• It has been established as first-line treatment for acute (first episode) and recurrent pericarditis on top of conventional therapy, as well as for prevention of postpericardiotomy syndrome. 4

Cardiovascular Disease (Emerging Indication)

• In patients after acute coronary syndrome (ACS), low-dose colchicine may be reasonable to reduce risk of major adverse cardiovascular events (MACE). 1
• The COLCOT trial showed that colchicine reduced the composite outcome of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent coronary revascularization by 32% when started within 30 days after MI. 1
• Annual influenza vaccination combined with colchicine therapy is recommended in ACS patients to reduce death and MACE. 1

Mechanism of Action

Colchicine works through multiple anti-inflammatory pathways: 3, 5

• Binds to tubulin and interferes with microtubular function in leukocytes
• Reduces neutrophil chemotaxis, margination, and aggregation
• Inhibits inflammasome signaling and decreases production of cytokines (particularly interleukin-1β)
• Prevents neutrophil extracellular trap release
• Reduces neutrophil-platelet interactions

Dosing Considerations

Adults

• FMF: 1.2 to 2.4 mg daily, increased in 0.3 mg increments as needed to control disease (maximum tolerated dose). 2
• Gout prophylaxis: 0.6 mg once or twice daily. 2
• Acute gout: 1.2 mg followed by 0.6 mg one hour later. 2
• Cardiovascular disease: 0.5 to 0.6 mg daily. 1

Pediatric (FMF only)

• Ages 4-6 years: 0.3 to 1.8 mg daily 2
• Ages 6-12 years: 0.9 to 1.8 mg daily 2
• Ages >12 years: 1.2 to 2.4 mg daily 2

Critical Safety Considerations

Drug Interactions

Colchicine is contraindicated in patients with liver or kidney problems who are taking strong CYP3A4 and/or P-glycoprotein inhibitors, as this combination can be fatal. 1, 2

High-risk interacting medications include: 1, 2

• Macrolides (clarithromycin, erythromycin)
• Azole antifungals (ketoconazole, itraconazole)
• HIV protease inhibitors (ritonavir, atazanavir, indinavir)
• Cyclosporine
• Verapamil
• Statins

Renal and Hepatic Impairment

• In patients with decreased renal function, the risk of toxicity is very high; monitor creatine phosphokinase (CPK) levels carefully and reduce dose accordingly. 1
• If liver enzymes are elevated >2-fold the upper normal limit, reduce the colchicine dose and investigate the cause. 1
• Colchicine is contraindicated in severe renal failure (creatinine clearance <15 mL/min). 1

Toxicity Recognition

Colchicine overdose can be fatal, with a narrow therapeutic index requiring careful monitoring. 1

Toxicity manifests in three stages: 1

• Stage 1 (0-24 hours): Gastrointestinal symptoms (abdominal cramping, vomiting, diarrhea), dehydration, shock, acute renal failure, seizures
• Stage 2 (24-72 hours): Multiorgan failure, bone marrow suppression, renal insufficiency, arrhythmias, disseminated intravascular coagulation, coma, death
• Stage 3 (recovery): Bone marrow recovery, rebound leukocytosis, resolution of organ failure, alopecia

Common Side Effects

• Gastrointestinal intolerance (diarrhea, nausea) occurs in approximately 10% of patients and is the most common reason for treatment withdrawal. 3, 4
• All patients in early trials experienced gastrointestinal symptoms at high doses (1 mg loading followed by 0.5 mg every 2 hours until toxicity). 1
• Lower doses (0.5 mg three times daily) may be sufficient and better tolerated. 1

Monitoring Requirements

• Response, toxicity, and compliance should be monitored every 6 months in stable FMF patients. 1
• Monitor complete blood counts and liver function tests regularly. 1
• In FMF, monitor inflammatory markers (SAA or CRP) at least every 3 months during dose escalation. 1
• More frequent monitoring (every 3 months) is needed when tapering biologics in FMF patients on combination therapy. 1

Common Pitfalls to Avoid

• Never discontinue colchicine during pregnancy or lactation in FMF patients—current evidence does not justify amniocentesis or treatment cessation. 1
• Do not use intravenous colchicine due to potential for severe and fatal toxicity. 1
• Avoid grapefruit and grapefruit juice, which can increase colchicine levels and risk of toxicity. 2
• Do not assume symptoms during colchicine therapy are always FMF attacks—patients remain susceptible to other conditions like appendicitis. 1
• Colchicine is not an analgesic and should not be used to treat pain from other causes. 2