Colchicine

Aka: Colchicine, Colcrys, Lodoco, Gloperba, Mitigare

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II. Indications

  1. Acute Pericarditis (off-label)
  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. Familial Mediterranean Fever
  5. 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

III. 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)

IV. 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

V. Medications

  1. Colchicine Tablets (Colcrys): 0.6 mg
  2. Colchicine Tablets (Lodoco): 0.5 mg
  3. Colchicine Capsules (Mitigare): 0.6 mg
  4. Colchicine Oral Solution (Gloperba): 0.6 mg/5 ml

VI. Dosing: Acute Gout Flare

  1. See Gouty Arthritis
  2. See below regarding renal dose adjustments and Drug Interactions
  3. Do NOT use Colchicine for acute gout in those with renal Impairment and already on Colchicine prophylaxis
  4. 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
  5. 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
  6. Endpoints
    1. Joint Pain improves
    2. Diarrhea
    3. Maximum Dose: 6 mg in 24 hours
  7. 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 (or use with caution on Hemodialysis)

VII. Dosing: Gout Prophylaxis

  1. See Gouty Arthritis
  2. Adult: 0.6 mg orally once to twice daily
  3. Limit dose to 0.3 mg orally daily in GFR <30 ml/min (with close monitoring)

VIII. Dosing: Familial Mediterranean Fever

  1. See below regarding renal dose adjustments and Drug Interactions
  2. Adult
    1. Dose 1.2 to 2.4 orally daily or divided twice daily
    2. Increase or decrease in 0.3 mg/day increments
    3. Limit dose to 0.3 mg orally daily in GFR <30 ml/min (with close monitoring)
  3. Child
    1. Age 4 to 6 years: 0.3 to 1.8 mg orally daily
    2. Age 6 to 12 years: 0.9 to 1.8 mg orally daily or divided twice daily
    3. Age >=12 years: Use adult dosing

IX. Dosing: Acute Pericarditis

  1. See Pericarditis
  2. Indicated as a second line agent in Pericarditis (in combination with NSAIDs or Corticosteroids)
  3. Dose 1-2 mg on day 1 and then 0.5 to 1 mg/day for 3 months (divided dosing)
    1. Colchicine weaned after CRP drops to <3
    2. Weight > 70 kg (154 lb): 0.5 mg twice daily
    3. Weight <70 kg (154 lb): 0.5 mg once daily
  4. Significantly reduces Pericarditis episode duration and recurrence rate
    1. Imazio (2005) Circulation 112: 2012-6
    2. Imazio (2013) N Engl J Med 369(16): 1522-8

X. Dosing: Cardiovascular Risk Reduction

  1. See Cardiovascular Risk Reduction
  2. Adjunct to other measures (e.g. Statin, Aspirin)
  3. Colchicine (Lodoco) 0.5 mg per day

XI. 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

XII. 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. Higher risk with renal Impairment or hepatic Impairment and advanced age
    2. Also higher risk with specific drugs (see Drug Interactions below)
      1. Colchicine
      2. Statin
      3. Fibrate

XIII. Safety

  1. Pregnancy Category C
  2. Considered safe in Lactation (but monitor infant for Diarrhea)
  3. Monitoring: Baseline and repeated at 1 month
    1. Complete Blood Count
    2. Liver transaminases (AST, ALT)
    3. Creatine Phosphokinase (CPK)
    4. Serum Creatinine

XIV. 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]

XV. Drug Interactions

  1. See other references for specific indication based dosing with Drug Interactions
  2. Strong CYP3A4 inhibitors (e.g. Clarithromycin, Itraconazole, Ritonavir)
    1. Do not use Colchicine with with Macrolides (e.g. Clarithromycin, Azithromycin, Erythromycin)
    2. Avoid concurrent use or significantly lower Colchicine dosing (e.g. 0.3 mg every other day)
  3. Moderate CYP3A4 Inhibitors (e.g. Ciprofloxacin, Verapamil)
    1. Lower Colchicine dosing (e.g. 0.3 mg daily or twice daily)
    2. Avoid Colchicine with regular intake of Grapefruit
  4. Drug Interactions also occur with P-Glycoprotein Inhibitors
    1. Avoid with Itraconazole
    2. Lower Colchicine dose (e.g. 0.3 mg once daily) with Cyclosporine, Ranolazine
  5. Rhabdomyolysis risk
    1. Increased risk when combined with Statins or Clarithromycin
    2. Increased risk with older patients and those with Chronic Kidney Disease

XVI. Resources

  1. Colchicine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7ef16d-262b-4dc0-92d6-7afe4aa21ebd

XVII. References

  1. (2011) Presc Lett 18(12): 70
  2. Borstad (2004) J Rheumatol 31:2429-32 [PubMed]

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Related Studies

Cost: Medications

colchicine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
COLCHICINE 0.6 MG CAPSULE Generic $4.15 each
COLCHICINE 0.6 MG TABLET Generic $0.37 each
colcrys (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
COLCRYS 0.6 MG TABLET Generic $0.37 each
mitigare (on 8/17/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MITIGARE 0.6 MG CAPSULE Generic $4.15 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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