What are the side effects of colchicine?

Side Effects of Colchicine

Gastrointestinal Side Effects (Most Common)

Gastrointestinal symptoms are the most frequent adverse effects of colchicine, occurring in nearly all patients at therapeutic doses, and include diarrhea, nausea, vomiting, abdominal cramping, and pain. 1

• Diarrhea is dose-dependent: High-dose regimens (1.2 mg followed by 0.6 mg/h for 6 hours) cause diarrhea in 77% of patients, while low-dose regimens (1.2 mg followed by 0.6 mg after 1 hour) reduce this to 23%, compared to 14% with placebo 1
• Gastrointestinal symptoms typically occur within the first 24 hours of treatment and affect up to 20% of patients at therapeutic doses 2
• These symptoms may signal impending toxicity and should prompt immediate evaluation 2
• All participants in controlled trials experienced gastrointestinal side effects (diarrhea and/or vomiting), with a number needed to harm of 1 3

Management of GI Side Effects

• Split the daily dose into multiple administrations to reduce symptom severity 1
• Temporarily reduce dairy products (lactose intolerance may contribute) 1
• Use antidiarrheal and spasmolytic agents as needed 1, 2
• Consider starting at subtherapeutic doses (0.5 mg/day) and gradually increasing by 0.5 mg increments 1

Serious and Life-Threatening Toxicity

Colchicine has a narrow therapeutic index with no clear distinction between toxic and lethal doses, and can cause multi-organ failure and death, particularly in patients with renal or hepatic impairment or when combined with CYP3A4/P-glycoprotein inhibitors. 2, 4, 5

Multi-Organ Dysfunction

Systemic toxicity develops in sequential phases 2, 5:

• Phase 1 (0-24 hours): Gastrointestinal symptoms mimicking gastroenteritis 5
• Phase 2 (24 hours to 7 days): Multi-organ dysfunction including:
  • Acute renal failure 2
  • Respiratory failure 2
  • Cardiac arrhythmias and impaired contractility 2, 5
  • Disseminated intravascular coagulation 2
  • Neurological alterations 2
  • Shock and sepsis 2, 5
• Phase 3 (weeks): Recovery or long-term sequelae 5

Lethal Doses

• The lowest reported lethal oral doses range from 7-26 mg 5
• High fatality rates occur after acute ingestions exceeding 0.5 mg/kg 5
• Death results from rapidly progressive multi-organ failure and sepsis 5

Hematologic and Neuromuscular Effects

Colchicine causes myelosuppression and neuromuscular toxicity, particularly in patients with renal impairment or when combined with certain medications. 4, 6, 7

Warning Signs Requiring Immediate Medical Attention 4:

• Muscle weakness or pain
• Numbness or tingling in fingers or toes
• Unusual bleeding or bruising
• Increased infections
• Weakness or fatigue
• Pale or gray color to lips, tongue, or palms

Myopathy Risk

• Combining colchicine with statins or fibrates significantly increases myopathy risk through additive muscle toxicity 6
• Ciclosporin co-administration can aggravate neuromuscular adverse effects 6

Other Adverse Effects

• Headache and fatigue occur infrequently 1
• Acute pancreatitis has been reported even with therapeutic dosing in elderly patients with renal impairment 7
• Abdominal pain is common in patients with familial Mediterranean fever 4

Critical Drug Interactions

Do not use colchicine in patients with liver or kidney problems who are taking CYP3A4 or P-glycoprotein inhibitors—serious side effects including death have been reported. 4

High-Risk Combinations 2, 4, 6:

• Macrolides (clarithromycin, erythromycin—not spiramycin): Risk of life-threatening pancytopenia 6
• Azole antifungals (ketoconazole): Increased colchicine concentrations 5
• Ciclosporin: Enhanced neuromuscular toxicity 6
• Statins and fibrates: Increased myopathy risk 6
• Grapefruit juice: Increases colchicine levels 4

Special Populations Requiring Dose Adjustment

Patients with renal or hepatic impairment require dose reductions to minimize toxicity risk. 2, 4

• Severe renal impairment (eGFR <30 mL/min): Avoid colchicine 2
• Cirrhosis: Elimination half-life may increase up to seven-fold 2
• Elderly patients: Use with extreme caution, particularly with pre-existing renal impairment 6, 7
• Maximum daily doses: 3 mg in adults, 2 mg in children for FMF 2

Pregnancy and Lactation

• Colchicine crosses the placenta but has not been shown to cause fetal toxicity 5
• It does not adversely affect reproductive potential in males or females 5
• Colchicine is excreted in breast milk and is considered compatible with lactation, though monitoring the infant for side effects is recommended 4, 5

Monitoring Requirements

• Monitor patients every 6 months for response, toxicity, and compliance 2
• Watch for early signs of toxicity, especially diarrhea, which is the earliest warning sign in patients with renal failure and the elderly 6
• No effective means exist to eliminate colchicine from tissues and blood once toxicity occurs—management is primarily supportive 2