Colchicine

Administration

• Type: Antigout
• Dosage Forms: Capsules, Tablets
• Routes of Administration: Oral
• Common Trade Names: Colcris; Mitigare (US), Jamp-Colchicine; PMS-Colchicine (Canadian)

Adult Dosing

Gout

• Flare treatment: Initial: 1.2mg and then 0.6mg in an hour (maximum 1.8mg within 1 hour). In patient receiving prophylaxis treatment wait for 12 h after flare dosing before resuming prophylaxis dose. Do not repeat treatment for at least 3 days (Canadian labelling recommendation)
• Prophylaxis Treatment: 0.6mg twice daily (maximum 1.2mg/day) for 3 months (without tophi) to 6 months (≥1 tophi) after reaching target serum uric acid levels

Familial Mediterranean Fever

• 1.2mg to 2.4mg per day in 1-2 decided dose. Titrate (increase or decrease) 0.3mg daily increment based on efficacy and adverse effects.

Pediatric Dosing

Familial Mediterranean Fever

• Children 4 to 6 years: 0.3 to 1.8mg daily in 1-2 divided doses
• Children 6 to 12 years: 0.9 to 1.8mg daily in 1-2 divided doses
• Adolescents >12 years: Adult dosing

Gout

• Prophylaxis/treatment: Adult dosing

Special Populations

• Pregnancy Rating: C
• Lactation risk: Colchicine enters breast milk, caution should be used when administering in a nursing woman.

Renal Dosing

• Adult:
  • Gout flare treatment:
    • Use colchicine to treat acute route flare is contraindicated in patients with renal impairment who are receiving colchicine for prophylaxis.
    • CrCl 30-80 mL/minute: dose adjustment not required, monitor closely for adverse effects.
    • CrCl <30 mL/minute: consider dose reduction, should not repeat dose more frequently that every 14 days.
    • Dialysis: A single dose of 0.6mg, should not repeat dose more frequently that every 14 days.
  • Gout prophylaxis:
    • CrCl 30-80 mL/minute: dose adjustment not required, monitor closely for adverse effects.
    • CrCl <30 mL/minute: nitial dose: 0.3mg daily, titrate with caution, monitor closely for adverse effects.
    • Dialysis: 0.3mg twice weekly, monitor closely for adverse effects.
  • FMF:
    • CrCl 30-80 mL/minute: monitor closely for adverse effects, consider dosage reduction.
    • CrCl <30mL/minute: Initial dose: 0.3mg daily, titrate with caution, monitor closely for adverse effects.
    • Dialysis: a single dose of 0.3mg, titrate with caution, monitor closely for adverse effects.

• Pediatric: Not defined

Hepatic Dosing

• Adult:
  • Mild to moderate impairment: use with caution, closely monitor for adverse effects.
  • Severe impairment: consider dosage adjustment.
• Pediatric: Not defined

Contraindications

• Allergy to class/drug
• Concomitant use with P-glycoprotein or strong CYP3A4 inhibitor in patients with renal or hepatic impairment
• Patient with both renal and hepatic impairment
• Serious gastrointestinal or cardiac disease

Adverse Reactions

Serious (<1%)

• Bone marrow suppression
• Disseminated intravascular coagulation
• Toxic neuromuscular disease
• Rhabdomyolysis
• Hepatotoxicity
• Hypersensitivity reaction

Common

• Diarrhoea
• Nausea
• Vomiting
• Abdominal cramp/abdominal pain
• Gout
• Pharyngolaryngeal pain
• Fatigue
• Headache

Pharmacology

• Half-life: 27 to 31 hours (multiple dose; young, healthy volunteers)
• Metabolism: Hepatic (CYP3A4)
• Excretion: Urine

Mechanism of Action

• Disrupts cytoskeleton function: inhibit beta-tubulin polymerization into microtubules.
• Prevent activation, migration and degranulation of neutrophils mediating some gout symptoms.

Toxicity

• Rapidly absorbed and extensively distributed
• Maximum therapeutic dose: 8-10 mg in 1 day
• Nausea, vomiting, abdominal pain, bloody diarrhea
• Lactic Acidosis
• Delirium, seizures, coma
• Death within 8-36 hours caused by respiratory failure or arrhythmia
• Aggressive supportive care (colchicine-specific antibodies are not available in U.S.)

References

Authors

Yajai Apibunyopas, Ross Donaldson, Ben Isakson, Neil Young