OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Colchicine	64-86-8	C22-H25-N-O6

ANNOTATED BIBLIOGRAPHY

References updated: 26 October 2017

• Zimmerman HJ. Drugs used to treat gout. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 543-4.

  (Expert review of hepatotoxicity published in 1999 states that: "despite long-term use of colchicine... , there is little evidence of its causing hepatic injury in humans").
• Grosser T, Smyth E, FitzGerald G. Pharmacology of gout. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 994-1004.

  (Textbook of pharmacology and therapeutics).
• Carr AA. Colchicine toxicity. Arch Intern Med 1965; 115: 29-33. [PubMed: 14219498]

  (36 year old man given high doses of colchicine [1.2-4 mg daily] developed fever, bone marrow suppression, and sepsis with accompanying rise in alkaline phosphatase [13 to 34 U/L] and AST [to ~90 U/L] without jaundice, ultimately resolving).
• Boruchow IB. Bone marrow depression associated with acute colchicine toxicity in the presence of hepatic dysfunction. Cancer 1966; 19: 541-3. [PubMed: 5933578]

  (69 year old man with obstructive jaundice due to pancreatic cancer developed fatal colchicine toxicity after taking a total dose of 14 mg over 6 days, whereupon he developed fever, bone marrow suppression and hypotension; underlying liver disease may have predisposed to toxicity).
• Bruns BJ. Colchicine toxicity. Australas Ann Med 1968; 17: 341-4. [PubMed: 5701926]

  (14 year old girl took overdose of colchicine [30 mg] and developed abdominal pain, vomiting and diarrhea followed by fever, pancytopenia, confusion, and seizures [bilirubin 1.7 mg/dL, AST 152 U/L, normal Alk P], alopecia appearing during recovery).
• Stemmermann GN, Hayashi T. Colchicine intoxication. A reappraisal of its pathology based on a study of three fatal cases. Hum Pathol 1971; 2: 321-32. [PubMed: 5095674]

  (Three cases of unintentional overdose of colchicine accompanied by vomiting, diarrhea, abdominal pain and followed by metabolic acidosis, renal and bone marrow failure, hypotension, stupor, widespread bleeding and death; liver abnormalities and hepatic necrosis on autopsy were frequent; etiology appears to be arrest of mitoses causing gastrointestinal and bone marrow failure).
• Ellwood MG, Robb GH. Self-poisoning with colchicine. Postgrad Med J 1971; 47: 129-38. [PMC free article: PMC2467157] [PubMed: 5576148]

  (Two women, ages 16 and 35 years, with intentional colchicine overdose developed nausea, vomiting, dehydration and hypotension followed by alopecia several weeks later; fatal case had centrolobular hepatic necrosis and fat).
• Domnguez de Villota E, Galdos P, Mosquera JM, Tomas MI. Colchicine overdose: an unusual origin of multiorgan failure. Crit Care Med 1979; 7: 278-9. [PubMed: 446061]

  (50 year old man took an overdose [30 mg] of colchicine and rapidly developed fever, diarrhea, vomiting, dehydration and hypotension with renal failure, acidosis, septicemia, and liver test abnormalities [bilirubin 0.7 rising to 6.6 mg/dL, AST 58 to 333 U/L, Alk P 91 to 667 U/L], but ultimate full recovery; sepsis and hypotension may have contributed to the liver abnormalities).
• Murray SS, Kramlinger KG, McMichan JC, Mohr DN. Acute toxicity after excessive ingestion of colchicine. Mayo Clin Proc 1983; 58: 528-32. [PubMed: 6876886]

  (15 year old girl took 2.4 mg of colchicine and rapidly developed nausea, weakness, hypotension, acidosis, respiratory failure and bone marrow suppression [no mention of bilirubin, AST 481 U/L, Alk P 595 U/L], ultimate recovery, alopecia on day 12).
• Rosalki SB, Foo AY. Alkaline phosphatase of possible renal origin identified in plasma after colchicine overdose. Clin Chem 1989; 35: 702-3. [PubMed: 2702760]

  (27 year old woman with colchicine overdose developed rising Alk P [135 rising to 639 U/L], which on analysis was identified as renal in origin).
• Baldwin LR, Talbert RL, Sampler R. Accidental overdose of insufflated colchicine. Drug Saf 1990; 5: 305-12. [PubMed: 2375835]

  (29 year old man and girlfriend snorted colchicine mistaking it for methamphetamine and developed nausea, diarrhea, fever, bone marrow suppression, renal failure and mild enzyme elevations [AST 311 U/L, Alk P 460 U/L], rapidly resolving in patient; the girl friend died).
• Putterman C, Ben-Chetrit E, Caraco Y, Levy M. Colchicine intoxication: clinical pharmacology, risk factors, features, and management. Semin Arthritis Rheum 1991; 21: 143-55. [PubMed: 1788551]

  (Overview of history, chemistry, pharmacokinetics, and side effects of colchicine focusing on features and management of overdose; mentions that liver damage from colchicine is uncommon, but has been described).
• Ben-Chetrit E, Levy M. Colchicine: 1998 Update. Semin Arthrit Rheum 1998; 28: 48-59. [PubMed: 9726336]

  (Review of history, structure, pharmacology, efficacy, side effects and indications of colchicine; overdose can cause cholera-like syndrome of diarrhea, dehydration and shock with renal, cardiac, hepatic, and bone marrow failure).
• Brvar M, Kozelj G, Mozina M, Bunc M. Acute poisoning with autumn crocus(Colchicum autumnale L.). Wien Klin Wochenschr 2004; 116: 205-8. [PubMed: 15088997]

  (71 year old woman ate autumn crocus and developed nausea, diarrhea followed by anemia with AST and LDH levels rising to 8 times ULN, resolving quickly and followed by alopecia during recovery).
• Livio Ndiaye F, Wiesel PH, Goy JJ, Genton A. [Abdominal pain and recurrent cholestatic jaundice] Praxis (Bern 1994) 2004; 93: 1051-4. French. [PubMed: 15318531]

  (70 year old man with heart and kidney transplants, developed jaundice and abdominal pain 1 month after starting colchicine and allopurinol [bilirubin 14.3 mg/dL, ALT 60 U/L, Alk P 244 U/L], resolving with stopping; then had acute abdominal pain and jaundice after 3 days of high doses of colchicine [total dose 7 mg] with bilirubin 5.6 mg/dL, ALT 20 U/L, Alk P 229 U/L, recovering quickly).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US between 2004 and 2008, more than 100 agents were implicated, but not colchicine).
• Kamath A, Mehal W, Jain D. Colchicine-associated ring mitosis in liver biopsy and their clinical implications. J Clin Gastroenterol 2008; 42: 1060-2. [PMC free article: PMC3730132] [PubMed: 18391833]

  (54 year old man with chronic hepatitis C taking colchicine [0.6 mg/day] had scattered mitotic figures in hepatocytes, in addition to chronic hepatitis on liver biopsy).
• Montiel V, Huberlant V, Vincent MF, Bonbled F, Hantson P. Multiple organ failure after an overdose of less than 0.4 mg/kg of colchicine: role of coingestants and drugs during intensive care management. Clin Toxicol (Phila) 2010; 48: 845-8. [PubMed: 20969505]

  PubMed Citation (33 year old woman developed severe diarrhea and hypotension within 24 hours of taking an overdose of colchicine [20 mg], ibuprofen [8 g], diclofenac [1 g], atorvastatin [100 mg] and furosemide [400 mg] with progressive multiorgan failure [bilirubin 1.0 rising to 17.2 mg/dL, ALT 41 to 4710 U/L, CK 211 to 26,990 U/L] over the next 14 days and death).
• Smith MW, Roberts DM, Ritson SM, Day RO. Death and morbidity from supratherapeutic dosing of colchicine. Med J Aust 2011; 194: 612-3. [PubMed: 21644880]

  (Short descriptions of 3 patients who developed severe nausea, vomiting, diarrhea, and myalgias within a few days of startng high doses of colchicine [2-4 mg daily]; one died of multiorgan failure, the other two recovered rapidly upon stopping, one had “hepatic dysfunction”).
• Iosfina I, Lan J, Chin C, Werb R, Levin A. Massive colchicine overdose with recovery. Case Rep Nephrol Urol 2012; 2: 20-4. [PMC free article: PMC3482071] [PubMed: 23197951]

  (47 year old woman took an overdose of colchicine [90 mg] and presented one hour later with abdominal pain, later developing respiratory, renal, cardiovascular and hepatic failure [AST rising from 29 to 15,111 U/L within 3 days], but ultimately recovered).
• Little A, Tung D, Truong C, Lapinsky S, Burry L. Colchicine overdose with coingestion of nonsteroidal antiinflammatory drugs. CJEM 2014; 16: 252-6. [PubMed: 24852590]

  (39 year old woman took an intentional multidrug overdose [25 mg colchicine, 1.25 g indomethacin, 75 mg zopiclone] and presented with severe nausea, vomiting and abdominal pain followed by shock, multiorgan failure and death 52 hours after the ingestion [ALT peak 1050 U/L, AST 4100 U/L, CPK 5,840 U/L, bilirubin not given]).
• Aghabiklooei A, Zamani N, Hassanian-Moghaddam H, Nasouhi S, Mashayekhian M. Acute colchicine overdose: report of three cases. Reumatismo 2014; 65: 307-11. [PubMed: 24705036]

  (Three cases of colchicine overdose, all presenting rapidly with nausea, abdominal pain and diarrhea, and two then developing metabolic acidosis, renal failure, cardiovascular collapse and death).
• Fernández S, Castro P, Nogué S, Nicolás JM. [Refractory shock and severe leukopenia with multisystemic organ failure due to colchicine intentional overdose]. Med Clin (Barc) 2014; 143 (3): 140. Spanish. [PubMed: 24378151]

  (24 year old man developed nausea and abdominal pain within hours of a colchicine overdose [30 mg], followed by acidosis and rhabdomyolysis [CPK 1128 U/L], bone marrow suppression, sepsis and then renal, cardioascular and pulmonary failure, dying 5 days after the ingestion).
• Kilic SC, Alaygut D, Unal E, Koç E, Patiroglu T. Acute colchicine intoxication complicated with extramedullary hematopoiesis due to filgrastim in a child. J Pediatr Hematol Oncol 2014; 36: e460-2. [PubMed: 24309614]

  (3 year old boy took an overdose of his mother's colchicine and developed nausea, vomiting and diarrhea followed by rhabdomyolysis, acidosis, neutropenia and sepsis, which was treated with recombinant G-CSF and was followed by leukocytosis and hepatomegaly which the authors attributed to extramedullary hematopoiesis).
• Shuttleworth E, Sawyer R, Holland M, Cooksley T. The perils of Grandma's medication: colchicine toxicity causing pneumomediastinum. Acute Med 2014; 13: 171-3. (19 year old man took an overdose of colchicine [50 mg] and developed refractory vomiting followed by subcutaneous and mediastinum emphysema, bone marrow suppression [white count 1100/µ . [PubMed: 25521087]

  L, platelets 4000/µL], and coagulopathy [prothrombin time 17.9 sec], but recovered with supportive therapy only).
• Boonstra JJ, Kan AA, de Vries I, Deneer VH, Meinders AJ. [A potentially fatal intoxication with colchicine]. Ned Tijdschr Geneeskd 2015; 159: A8144. Dutch. [PubMed: 25804106]

  (18 year old woman took an overdose of colchicine [30 mg] and developed abdominal pain and vomiting followed by anema, thrombocytopenia and paralytic ileus requiring intensive care, but with ultimate recovery; no liver test results provided).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to colchicine).
• Arslan MN, Özgün A, Daş T, Kumru D, Şam B, Koç S. Colchicine-induced rhabdomyolysis: An Autopsy Case. Am J Forensic Med Pathol 2016; 37: 57-9. [PubMed: 27049658]

  (18 year old woman with familial Mediterranean fever developed fatal rhabdomyolysis and shock after a colchicine overdose (4.5 mg), and had moderate fatty liver at autopsy).
• Alaygut D, Kilic SC, Kaya A, Oflaz MB, Bolat F, Cevit Ö, Icagasioglu FD. Assessment of 17 pediatric cases With colchicine poisoning in a 2-year period. Pediatr Emerg Care 2016; 32: 168-72. [PubMed: 26928096]

  (Over a 2 year period, 17 children, ages 1 to 17 years, were admitted to a Turkish referral center for colchicine overdose, 6 had Familial Mediterranean fever and the others had swallowed family members' drug, 8 were symptomatic with nausea, abdominal pain or diarrhea, serum enyzme elevations arose in 2 patients, but were likely due to rhabdomyolysis [peak ALT 119 and 646 U/L, AST 3357 and 3003, CPK 3700 and 75,643 U/L]; all survived).
• Lloyd G. Colchicine in overdose. Br J Gen Pract 2016; 66: 605. [PMC free article: PMC5198648] [PubMed: 27884896]

  (The author reminds readers: "Please be aware of the devasting consequences of a significant colchicine overdose").
• Roddy E, Mallen CD. Colchicine in overdose. Br J Gen Pract. 2017; 67: 61. [PMC free article: PMC5308094] [PubMed: 28126860]

  (In answer to Lloyd [2016] "We urge prescribers not to abandon an effective treatment for this excruciatingly painful...condition").