Colchicine

Colchicine

  • An alkaloid from Colchicum Autumnale 
  • Pregnancy category C (safe with breastfeeding)

  • 0.6 mg orally, twice–three times/day (Dose reduction recommended in severe renal/hepatic impairment)
  • Long ½ life of 20- 40 hours 
  • Drug must be shielded from light (degraded by ultraviolet radiation)

  • Metabolized through liver
  • Mainly excreted in bile/feces
  • 10-20% excreted in urine unchanged

Antimitotic & anti-inflammatory

Binds to tubulin leading to microtubules assembly inhibition and mitotic arrest at metaphase:

  • concentrates in leukocytes, & via microtubule inhibition leads to decreased neutrophil motility, chemotaxis & adhesiveness to endothelium
  • Interferes with lysosomal degranulation

Food and drug administration (FDA)

  • Gout
  • Familial Mediterranean fever

Off label

  • Neutrophilic (Pyoderma gangrenosum, sweets, Behçet, aphthous stomatitis)
  • Vasculitis (leukocytoclastic vasculitis, urticarial vasculitis)
  • Pustular psoriasis
  • linear IgA bullous dermatosis, dermatitis herpetiformis, epidermolysis bullosa equiseta, IgA pemphigus 
  • Autoimmune connective tissue disease (dermatomyositis, systemic sclerosis, relapsing polychondritis)

Absolute

  • Hypersensitivity
  • Blood dyscrasias

Relative

  • Gastrointestinal, renal, hepatic, cardiac disorders
  • Concomitant use of P-glycoprotein inhibitors & strong CYP3A4 inhibitors

Gastrointestinal (#1), dose related nausea, abdominal pain, diarrhea 

  • Bone marrow suppression (especially with renal insufficiency & prolonged therapy)
  • Myopathy
  • Peripheral neuropathy
  • Alopecia
  • Azoospermia 
  • Megaloblastic anemia (Vitamin B12 deficiency)

Overdose

  • Cholera-like syndrome (dehydration, hypokalemia, hyponatremia, metabolic acidosis, renal failure)
  • Multi-organ failure (respiratory distress syndrome, disseminated intravascular coagulation, central nervous system, bone marrow failure), epidermal necrolysis

  • Mainly through P-glycoprotein inhibitors for example cyclosporine & CYP3A4 inhibitors

Baseline

  • Complete blood count, chemistry profile, urinalysis

Follow-up

  • Complete blood count monthly for 1st several months then every 3-6 months 

Drugs that inhibit microtubular assembly in dermatology

  • – Colchicine
  • – Podophyllotoxin
  • – Griseofulvin
  • – Albendazole
  • – Taxanes & Vinca alkaloids 
  • – Tirbanibulin