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 [1]

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

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
  • Bone marrow suppression, renal failure
  • 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.)
  • If survival, can see rebound leukocytosis and transient alopecia

Comments

See Also

References

  1. Khanna D. et al.2012 ACR Guidelines for Management of Gout Part I: Systemic Non-pharmacologic and Pharmacologic Therapeutic Approach to Hyperuricemia. Arthritis Care Res (Hoboken). 2012 Oct; 64(10): 1431–1446.