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Colchicine

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Colchicine, Colcrys, Lodoco

  • See Also
  1. Colchicine Toxicity
  • Indications
  1. Acute Pericarditis
  2. Cardiovascular Risk Reduction
    1. Refractory, recurrent cardiovascular events despite maximal Cardiovascular Risk Reduction AND eGFR >60 ml/min
  3. Acute Gouty Arthritis (adjunct to NSAIDs)
  4. Gout prophylaxis (started with Allopurinol to prevent triggering acute attack)
    1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227796.htm
    2. Less viable option (too expensive) now that generic preparations were removed from the market
    3. Use NSAIDs instead, until generic pricing again
  • Contraindications
  1. Severe renal or liver disease (see adverse effects below)
    1. If used, limit to the 3 dose protocol below and do not repeat for 2 weeks
    2. Do not use with Cyclosporine or Cytochrome P450 3A4 Inhibitor if severe liver or renal disease (lethal interaction)
  • Mechanism
  1. Alkaloid isolated from Colchicum autumnale (Autumn crocus)
  2. Anti-gout and anti-inflammatory properties
  3. Colchicine binds tubulin, inhibiting its polymerization, and blocking microtubule formation in mitosis
  4. Decreases inflammatory response
    1. Inhibits chemotaxis, migration and Phagocytosis of Leukocytes and other inflammatory cells
    2. Gastrointestinal cells and Red Blood Cells are affected first due to their rapid division cycles
  5. May also inhibit monosodium urate crystal deposition in joint tissues
  1. See Gout for prophylaxis protocol when starting allopurinal
  2. Tolerable Protocol (as adjunct to NSAIDs)
    1. Start within 24 hours of attack
    2. Option 1: Colchicine 0.6 mg orally twice daily
    3. Option 2: Colchicine 0.6 mg two taken immediately, then a third one hour later
      1. New protocol (2010) - recommended dosing for Colcrys
  3. Old Protocol (Not recommended - poorly tolerated due to Diarrhea, serious toxicity)
    1. Start: 1.0 mg given within 24 hours of attack
    2. Then: 0.5 mg each hour or 1.0 mg every 2 hours prn
  4. Endpoints
    1. Joint Pain improves
    2. Diarrhea
    3. Maximum Dose: 6 mg in 24 hours
  1. See Cardiovascular Risk Reduction
  2. Adjunct to other measures (e.g. Statin, Aspirin)
  3. Colchicine (Lodoco) 0.5 mg per day
  • Dosing
  • Renal dose adjustment
  1. GFR >50 ml/minute: 0.6 mg orally twice daily
  2. GFR 35-50 ml/minute: 0.6 mg orally once daily
  3. GFR 10-34 ml/minute: 0.6 mg orally every 2-3 days
  4. GFR <10 ml/minute: Do NOT use
  • Adverse Effects
  1. Narrow dosing range
    1. See Colchicine Toxicity
  2. Gastrointestinal toxicity (limits dosing)
    1. Nausea or Vomiting
    2. Diarrhea
  3. Bone Marrow suppression (esp. if severe liver or renal disease)
  4. Reversible Axonal Neuromyopathy (1% of cases)
    1. Increased risk if severe liver or renal disease
  5. Alopecia
  6. Rhabdomyolysis
    1. See Drug Interactions below
  • Safety
  1. Pregnancy Category C
  2. Unknown safety in Lactation
  • Efficacy
  1. Cardiovascular Risk Reduction
    1. Reduced cardiovascular event rates in those at risk (NNT 36)
    2. Also reduced risk of events after Myocardial Infarction
    3. Nidorf (2020) N Engl J Med 383(19):1838-47 [PubMed]
    4. Tardif (2019) N Engl J Med 381(26):2497-505 [PubMed]
  • Monitoring
  • Baseline and repeated at 1 month
  1. Complete Blood Count
  2. Liver transaminases (AST, ALT)
  3. Creatine Phosphokinase (CPK)
  4. Serum Creatinine
  • Pharmacokinetics
  1. Oral Bioavailability: 25 to 40%
  2. Volume of Distribution: >2 L/kg (as high as 21 L/kg in Overdose)
  3. Serum Elimination Half-Life: 8 to 9 hours up to 30 hours
    1. However, remains in adipose tissue for days
  4. Hepatic metabolism to Styrene epoxide
  5. Renal Clearance (20 to 30%)
  6. Narrow Therapeutic Index
    1. See Colchicine Toxicity
  • Drug Interactions
  1. Cyclosporine
  2. Cytochrome P450 3A4 inhibitors (e.g. Clarithromycin, Verapamil)
    1. Do not use with with Macrolides (e.g. Clarithromycin, Azithromycin, Erythromycin)
    2. Avoid Grapefruit
  3. Drug Interactions also occur with P-Glycoprotein Inhibitors
    1. Avoid Itraconazole
  4. Rhabdomyolysis risk
    1. Increased risk when combined with Statins or Clarithromycin
    2. Increased risk with older patients and those with Chronic Kidney Disease
  • Resources
  1. Colchicine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7ef16d-262b-4dc0-92d6-7afe4aa21ebd
  • References
  1. (2011) Presc Lett 18(12): 70
  2. Borstad (2004) J Rheumatol 31:2429-32 [PubMed]