Colchicine

Acute Pericarditis (off-label)
Cardiovascular Risk Reduction
1. Refractory, recurrent cardiovascular events despite maximal Cardiovascular Risk Reduction AND eGFR >60 ml/min
Acute Gouty Arthritis (adjunct to NSAIDs)
Familial Mediterranean Fever
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

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)

Alkaloid isolated from Colchicum autumnale (Autumn crocus)
Anti-gout and anti-inflammatory properties
Colchicine binds tubulin, inhibiting its polymerization, and blocking microtubule formation in Mitosis
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
May also inhibit monosodium urate crystal deposition in joint tissues

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

See below regarding renal dose adjustments and Drug Interactions
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)
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

See Pericarditis
Indicated as a second line agent in Pericarditis (in combination with NSAIDs or Corticosteroids)
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
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

Oral Bioavailability: 25 to 40%
Volume of Distribution: >2 L/kg (as high as 21 L/kg in Overdose)
Serum Elimination Half-Life: 8 to 9 hours up to 30 hours
1. However, remains in adipose tissue for days
Hepatic metabolism to Styrene epoxide
Renal Clearance (20 to 30%)
Narrow Therapeutic Index
1. See Colchicine Toxicity

Narrow dosing range
1. See Colchicine Toxicity
Gastrointestinal toxicity (limits dosing)
1. Nausea or Vomiting
2. Diarrhea
Bone Marrow suppression (esp. if severe liver or renal disease)
Reversible Axonal Neuromyopathy (1% of cases)
1. Increased risk if severe liver or renal disease
Alopecia
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

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

See other references for specific indication based dosing with Drug Interactions
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)
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
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
Rhabdomyolysis risk
1. Increased risk when combined with Statins or Clarithromycin
2. Increased risk with older patients and those with Chronic Kidney Disease