Colchicine

BRAND NAMES

Colchicine is marketed under various brand names worldwide, which differ based on the country and manufacturer. Some of the most widely recognized brand names in the United States and around the world include:

U.S. Brand Names

• Colcrys

• Mitigare

• Gloperba

• Lodoco 

International and Other Brand Names

• Colchicindon

• Colchicum-Dispert

• Colchigo

MECHANISM OF ACTION

Colchicine works mainly by interrupting the inflammatory process through binding to tubulin and preventing its polymerization, thereby blocking microtubule formation. This disruption hinders the activity of white blood cells—especially neutrophils—by inhibiting their movement, activation, and degranulation. As a result, colchicine also suppresses the inflammasome pathway and decreases the release of pro-inflammatory cytokines. Through these actions, it effectively reduces inflammation linked to conditions such as gout and Familial Mediterranean Fever (FMF).

PHARMACOKINETICS:         

Absorption

After oral administration, colchicine is quickly and efficiently absorbed, mainly in the jejunum and ileum of the small intestine. Maximum plasma levels are usually achieved within 0.5 to 3 hours following ingestion.

Distribution

Colchicine is a lipid-soluble alkaloid that distributes rapidly and extensively throughout the body, reaching various tissues and organs. Its concentration within leukocytes (white blood cells) is notably higher than that found in plasma.

Metabolism

Colchicine undergoes primary metabolism in the liver and gastrointestinal tract, mainly through the action of the cytochrome P450 enzyme CYP3A4 and the efflux transporter P-glycoprotein (P-gp).

Excretion

Colchicine is mainly excreted by the liver into the bile, with a small amount eliminated through the kidneys. It also undergoes considerable enterohepatic recirculation.

PHARMACODYNAMICS

The pharmacodynamics of colchicine are primarily centered on its ability to bind to the protein tubulin, thereby disrupting the formation and function of microtubules. This disruption has significant anti-inflammatory effects, particularly within leukocytes (white blood cells), and is the key to its therapeutic action in conditions like gout and Familial Mediterranean Fever (FMF). 

ADMINISTRATION

Colchicine is typically administered orally in the form of tablets or capsules. For acute gout attacks, it is usually given in a higher initial dose followed by smaller doses until symptoms improve. In chronic use, lower doses are prescribed to prevent recurrent gout flares or manage familial Mediterranean fever. It is important to take colchicine exactly as directed to avoid toxicity, as the therapeutic dose is close to the toxic dose. Patients with liver or kidney impairment may require dose adjustments under medical supervision.

DOSAGE AND STRENGTH

Colchicine is available in oral tablet or capsule forms, commonly in strengths of 0.5 mg and 0.6 mg. For acute gout attacks, an initial dose of 1.2 mg is often followed by 0.6 mg one hour later, then 0.6 mg once or twice daily until symptoms subside. For prevention of recurrent gout or management of familial Mediterranean fever, lower doses of 0.6 mg once or twice daily are typically used. Dosage may need adjustment in patients with kidney or liver impairment to reduce the risk of toxicity. Treatment should always follow a physician’s guidance due to colchicine’s narrow therapeutic range.

DRUG INTERACTIONS

Colchicine has numerous important drug interactions, mainly because it is metabolized by the CYP3A4 enzyme and transported by P-glycoprotein (P-gp). Drugs that inhibit these pathways can cause dangerously high colchicine levels in the body, raising the risk of serious side effects such as muscle damage (myopathy or rhabdomyolysis), blood disorders, and organ failure.

FOOD INTERACTIONS

Colchicine has minimal direct food interactions, meaning it can generally be taken with or without food. However, taking it with a large meal may slow absorption slightly, potentially delaying its effect. Grapefruit and grapefruit juice should be avoided, as they can inhibit the CYP3A4 enzyme, increasing colchicine levels and the risk of toxicity. Alcohol does not directly interact with colchicine but may exacerbate gastrointestinal side effects.

CONTRAINDICATIONS

Colchicine is contraindicated in individuals with known hypersensitivity to colchicine or any of its components. It should not be used in patients with severe kidney or liver impairment, as accumulation can lead to toxicity. It is also contraindicated in individuals with pre-existing blood disorders or gastrointestinal conditions that increase the risk of severe side effects. Concurrent use with strong CYP3A4 or P-glycoprotein inhibitors in vulnerable patients is generally avoided due to the risk of life-threatening toxicity. Additionally, colchicine is contraindicated during pregnancy and breastfeeding unless specifically prescribed by a physician.

SIDE EFFECTS

• Diarrhea (the most frequent side effect)

• Nausea

• Vomiting

• Abdominal discomfort or cramps

• Headaches

• Fatigue or overall weakness

OVER DOSE

An overdose of colchicine can be life-threatening and requires immediate medical attention. Symptoms may include severe nausea, vomiting, diarrhea, abdominal pain, muscle weakness, low blood pressure, irregular heartbeat, and organ failure. Colchicine toxicity can progress rapidly, leading to bone marrow suppression, multi-organ failure, and potentially death. There is no specific antidote, so treatment focuses on supportive care, such as activated charcoal if ingested recently, fluid management, and monitoring of vital organ functions. Early medical intervention is critical to improve outcomes.

TOXICITY

Colchicine toxicity is a life-threatening poisoning with a narrow therapeutic index and no specific antidote. It causes widespread, multi-organ damage by disrupting microtubules, which are vital for cell division and function.