II. Indications
- Acute Pericarditis
-
Cardiovascular Risk Reduction
- Refractory, recurrent cardiovascular events despite maximal Cardiovascular Risk Reduction AND eGFR >60 ml/min
- Acute Gouty Arthritis (adjunct to NSAIDs)
-
Gout prophylaxis (started with Allopurinol to prevent triggering acute attack)
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227796.htm
- Less viable option (too expensive) now that generic preparations were removed from the market
- Use NSAIDs instead, until generic pricing again
III. Contraindications
- Severe renal or liver disease (see adverse effects below)
- If used, limit to the 3 dose protocol below and do not repeat for 2 weeks
- Do not use with Cyclosporine or Cytochrome P450 3A4 Inhibitor if severe liver or renal disease (lethal interaction)
IV. Mechanism
- 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
- Inhibits chemotaxis, migration and Phagocytosis of Leukocytes and other inflammatory cells
- 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
V. Dosing: Gout in normal Renal Function
- See Gout for prophylaxis protocol when starting allopurinal
- Tolerable Protocol (as adjunct to NSAIDs)
- Start within 24 hours of attack
- Option 1: Colchicine 0.6 mg orally twice daily
- Option 2: Colchicine 0.6 mg two taken immediately, then a third one hour later
- New protocol (2010) - recommended dosing for Colcrys
- Old Protocol (Not recommended - poorly tolerated due to Diarrhea, serious toxicity)
- Start: 1.0 mg given within 24 hours of attack
- Then: 0.5 mg each hour or 1.0 mg every 2 hours prn
- Endpoints
- Joint Pain improves
- Diarrhea
- Maximum Dose: 6 mg in 24 hours
VI. Dosing: Cardiovascular Risk Reduction
- See Cardiovascular Risk Reduction
- Adjunct to other measures (e.g. Statin, Aspirin)
- Colchicine (Lodoco) 0.5 mg per day
VII. Dosing: Renal dose adjustment
- GFR >50 ml/minute: 0.6 mg orally twice daily
- GFR 35-50 ml/minute: 0.6 mg orally once daily
- GFR 10-34 ml/minute: 0.6 mg orally every 2-3 days
- GFR <10 ml/minute: Do NOT use
VIII. Adverse Effects
- Narrow dosing range
- Gastrointestinal toxicity (limits dosing)
- Bone Marrow suppression (esp. if severe liver or renal disease)
- Reversible Axonal Neuromyopathy (1% of cases)
- Increased risk if severe liver or renal disease
- Alopecia
-
Rhabdomyolysis
- See Drug Interactions below
IX. Safety
- Pregnancy Category C
- Unknown safety in Lactation
X. Efficacy
-
Cardiovascular Risk Reduction
- Reduced cardiovascular event rates in those at risk (NNT 36)
- Also reduced risk of events after Myocardial Infarction
- Nidorf (2020) N Engl J Med 383(19):1838-47 [PubMed]
- Tardif (2019) N Engl J Med 381(26):2497-505 [PubMed]
XI. Monitoring: Baseline and repeated at 1 month
- Complete Blood Count
- Liver transaminases (AST, ALT)
- Creatine Phosphokinase (CPK)
- Serum Creatinine
XII. Pharmacokinetics
- 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
- However, remains in adipose tissue for days
- Hepatic metabolism to Styrene epoxide
- Renal Clearance (20 to 30%)
- Narrow Therapeutic Index
XIII. Drug Interactions
- Cyclosporine
-
Cytochrome P450 3A4 inhibitors (e.g. Clarithromycin, Verapamil)
- Do not use with with Macrolides (e.g. Clarithromycin, Azithromycin, Erythromycin)
- Avoid Grapefruit
-
Drug Interactions also occur with P-Glycoprotein Inhibitors
- Avoid Itraconazole
-
Rhabdomyolysis risk
- Increased risk when combined with Statins or Clarithromycin
- Increased risk with older patients and those with Chronic Kidney Disease
XIV. Resources
XV. References
- (2011) Presc Lett 18(12): 70
- Borstad (2004) J Rheumatol 31:2429-32 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
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 |