What are the adverse effects of colchicine?

From the Guidelines

Colchicine is associated with significant adverse effects, including gastrointestinal issues, such as diarrhea, nausea, vomiting, cramps, and pain, as well as headache and fatigue, particularly in patients with renal or hepatic impairment. The most common adverse effects of colchicine are gastrointestinal in nature, including diarrhea, nausea, vomiting, cramps, and pain, which are reported to occur in patients taking the medication 1. Other less common adverse effects include headache and fatigue 1. It is essential to note that colchicine is contraindicated in patients with renal or hepatic impairment who are using potent cytochrome P450 3A4 inhibitors or P-glycoprotein inhibitors 1. To minimize the risk of adverse effects, low-dose colchicine is recommended when using colchicine to treat acute gout, with a suggested regimen of 1.2 mg followed by 0.6 mg 1 hour later 1. Key considerations for the use of colchicine include:

• Gastrointestinal adverse effects are common
• Patients with renal or hepatic impairment are at increased risk of toxicity
• Concomitant use of certain medications, such as CYP3A4 inhibitors, can increase the risk of adverse effects
• Low-dose regimens can reduce the risk of gastrointestinal adverse effects while maintaining efficacy 1.

From the FDA Drug Label

The most commonly reported adverse reaction in clinical trials of colchicine for the prophylaxis of gout was diarrhea. The most common adverse reactions reported in the clinical trial with Colchicine Tablets, USP for treatment of gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%) Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating Colchicine Tablets, USP, usually presenting within 24 hours, and occurring in up to 20% of patients given therapeutic doses. Typical symptoms include cramping, nausea, diarrhea, abdominal pain and vomiting Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. The following adverse reactions have been reported with colchicine: * Neurological: sensory motor neuropathy * Dermatological: alopecia, maculopapular rash, purpura, rash * Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting * Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia * Hepatobiliary: elevated AST, elevated ALT * Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis * Reproductive: azoospermia, oligospermia

The adverse effects of colchicine include:

• Gastrointestinal effects: diarrhea, nausea, abdominal pain, vomiting, and cramping
• Neurological effects: sensory motor neuropathy
• Dermatological effects: alopecia, maculopapular rash, purpura, and rash
• Hematological effects: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia
• Hepatobiliary effects: elevated AST and ALT
• Musculoskeletal effects: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, and rhabdomyolysis
• Reproductive effects: azoospermia and oligospermia
• Other effects: myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous systems 2

From the Research

Adverse Effects of Colchicine

The adverse effects of colchicine can be severe and life-threatening. Some of the key adverse effects include:

• Gastrointestinal symptoms such as nausea, vomiting, and diarrhea, which can occur in 5-10% of patients 3
• Myelosuppression, myoneuropathy, and multiple organ failure, which can occur with intentional overdose or therapeutic dosing in patients with reduced clearance of colchicine due to pre-existing renal or hepatic impairment 4
• Acute pancreatitis, which has rarely been reported and only in association with severe colchicine overdose accompanied by multi-organ failure, but can also occur with therapeutic dosing in patients with pre-existing renal impairment 4
• Multi-organ dysfunction and failure, which can result from the disruption of microtubular networks and lead to impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility 5
• Increased risk of myopathy when co-administered with statins 5

Factors Contributing to Adverse Effects

Several factors can contribute to the adverse effects of colchicine, including:

• Dose: High doses of colchicine can increase the risk of adverse effects, with a high fatality rate reported after acute ingestions exceeding 0.5 mg/kg 5
• Drug interactions: Inhibitors of CYP3A4 and P-glycoprotein, such as clarithromycin, erythromycin, ketoconazole, and ciclosporin, can increase colchicine concentrations and increase the risk of adverse effects 5
• Renal or hepatic impairment: Patients with pre-existing renal or hepatic impairment may be at increased risk of adverse effects due to reduced clearance of colchicine 5, 4
• Age: Elderly patients may be at increased risk of adverse effects due to age-related changes in renal function and drug metabolism 4

Clinical Presentation

Colchicine poisoning can present in three sequential and usually overlapping phases:

• Gastrointestinal phase: 10-24 hours after ingestion, characterized by gastrointestinal symptoms such as nausea, vomiting, and diarrhea 5
• Multi-organ dysfunction phase: 24 hours to 7 days after ingestion, characterized by multi-organ dysfunction and failure 5
• Recovery phase: typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness 5