DIRA 1.0: Atlas of Drug-induced Rhabdomyolysis

COLCHICINE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Moderate-DIR concern

Severity Score:3

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

WARNINGS AND PRECAUTIONS
Neuromuscular Toxicity
Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid, or benzafibrate (themselves associated with myotoxicity) or cyclosporine with COLCRYS may potentiate the development of myopathy [see DRUG INTERACTIONS (7)]. Once colchicine is stopped, the symptoms generally resolve within 1 week to several months.
ADVERSE REACTIONS
Postmarketing Experience
Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous systems.
These most often occur with excessive accumulation or overdosage [see OVERDOSAGE (10)].
The following adverse reactions have been reported with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine.
Neurological: sensory motor neuropathy
Dermatological: alopecia, maculopapular rash, purpura, rash
Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting
Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia
Hepatobiliary: elevated AST, elevated ALT
Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis
Reproductive: azoospermia, oligospermia
DRUG INTERACTIONS
COLCRYS (colchicine) is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine. If COLCRYS is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely. Fatal drug interactions have been reported.
Physicians should ensure that patients are suitable candidates for treatment with COLCRYS and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction. Signs and symptoms of COLCRYS toxicity should be evaluated promptly and, if toxicity is suspected, COLCRYS should be discontinued immediately.
Table 4 provides recommendations as a result of other potentially significant drug interactions. Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

Rhabdomyolysis

42850

Other ADRs

1456

14115823

Odds Ratio = 14.028

Drug Property Information

ATC Code(s):

M04AC01 - colchicine

M04AC - Preparations with no effect on uric acid metabolism
M04A - ANTIGOUT PREPARATIONS
M04 - ANTIGOUT PREPARATIONS
M - MUSCULO-SKELETAL SYSTEM

Active Ingredient:colchicine

Active Ingredient UNII:SML2Y3J35T

Drugbank ID:DB01394

PubChem Compound:2833

CAS Number:64-86-8

Dosage Form(s):tablet, film coated

Route(s) Of Administrator:oral

Daily Dose:

1.0 mg/day M04AC01

Chemical Structure:

SMILE Code:
CC(=O)NC1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC

Reference

COHORT STUDY:

1: Rhabdomyolysis: an evaluation of 475 hospitalized patients.

[Melli G, Chaudhry V, Cornblath DR, Medicine (Baltimore). 2005 Nov;84(6):377-85.]

ABSTRACT

Rhabdomyolysis is a common and potentially lethal clinical syndrome that results from acute muscle fiber necrosis with leakage of muscle constituents into blood. Myoglobinuria is the most significant consequence, leading to acute renal failure (ARF) in 15%-33% of patients with rhabdomyolysis. Rhabdomyolysis occurs from inherited diseases, toxins, muscle compression or overexertion, or inflammatory processes, among other disorders. In some cases, no cause is found. We describe 475 patients from the Johns Hopkins Hospital inpatient records between January 1993 and December 2001 for the following discharge diagnosis codes: myoglobinuria, rhabdomyolysis, myopathy, toxic myopathy, malignant hyperthermia, neuroleptic malignant syndrome, and polymyositis. Of 1362 patients, 475 patients with an acute neuromuscular illness with serum creatine kinase (CK) more than 5 times the upper limit of normal (>975 IU/L) were included. Patients with recent myocardial infarction or stroke were excluded. The etiology was assigned by chart review. For all, the highest values of serum CK, serum creatinine and urine myoglobin, hemoglobin, and red blood cells were recorded. Forty-one patients had muscle biopsy within at least 2 months from the onset of rhabdomyolysis.Of the 475 patients, 151 were female and 324 were male (median age, 47 yr; range, 4-95 yr). Exogenous toxins were the most common cause of rhabdomyolysis, with illicit drugs, alcohol, and prescribed drugs responsible for 46%. Among the medical drugs, antipsychotics, statins, zidovudine, colchicine, selective serotonin reuptake inhibitors, and lithium were the most frequently involved. In 60% of all cases, multiple factors were present. In 11% of all cases, rhabdomyolysis was recurrent. Underlying myopathy or muscle metabolic defects were responsible for 10% of cases, in which there was a high percentage of recurrence, only 1 etiologic factor, and a low incidence of ARF. In 7%, no cause was found. ARF was present in 218 (46%) patients, and 16 died (3.4%). A linear correlation was found between CK and creatinine and between multiple factors and ARF, but there was no correlation between ARF and death or between multiple factors and death. Urine myoglobin detected by dipstick/ultrafiltration was positive in only 19%. Toxins are the most frequent cause of rhabdomyolysis, but in most cases more than 1 etiologic factor was present. Patients using illicit drugs or on prescribed polytherapy are at risk for rhabdomyolysis. The absence of urine myoglobin, by qualitative assay, does not exclude rhabdomyolysis. With appropriate care, death is rare.

PMID: 16267412

OTHER REFERENCE(S):

1: Severe hypertriglyceridemia and colchicine intoxication following suicide attempt.

[Lev Shaul,Snyder David,Azran Carmil,Zolotarsky Victor,Dahan Arik]
Drug Des Devel Ther.2017 Nov 22;11:3321-3324. doi: 10.2147/DDDT.S140574. eCollection 2017. PMID: 29200827

2: Colchicine intoxication in familial Mediterranean fever patients using clarithromycin for the treatment of Helicobacter pylori: a series of six patients.

[Haj Yahia Soad,Ben Zvi Ilan,Livneh Avi]
Rheumatol Int.2018 Jan;38(1):141-147. doi: 10.1007/s00296-017-3823-1. Epub 2017 Oct 3. PMID: 28975396

3: Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report.

[Frydrychowicz Clara,Pasieka Bastian,Pierer Matthias,Mueller Wolf,Petros Sirak,Weidhase Lorenz]
J Med Case Rep.2017 Jan 4;11(1):8. doi: 10.1186/s13256-016-1169-z. PMID: 28049514

4: Poster 97 Statin-Induced Rhabdomyolysis Triggered by Concomitant Colchicine Administration: A Case Report.

[Auriemma Michael J,Bunning Robert D]
PM R.2016 Sep;8(9S):S193. doi: 10.1016/j.pmrj.2016.07.140. Epub 2016 Sep 24. PMID: 27672864

5: An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function.

[Patel Shyam,Andres Jennifer,Qureshi Kamran]
Case Rep Med.2016;2016:3191089. doi: 10.1155/2016/3191089. Epub 2016 Aug 22. PMID: 27635145

6: Colchicine-Induced Rhabdomyolysis: An Autopsy Case.

[Arslan Murat Nihat,Özgün Ayşe,Daş Taner,Kumru Durmuş,Şam Bülent,Koç Sermet]
Am J Forensic Med Pathol.2016 Jun;37(2):57-9. doi: 10.1097/PAF.0000000000000225. PMID: 27049658

7: Thiocolchicoside: review of adverse effects.

Prescrire Int.2016 Feb;25(168):41-3. PMID: 27042729

8: Progressive Organ Failure After Ingestion of Wild Garlic Juice.

[Galland-Decker Coralie,Charmoy Alexia,Jolliet Philippe,Spertini Olivier,Hugli Olivier,Pantet Olivier]
J Emerg Med.2016 Jan;50(1):55-60. doi: 10.1016/j.jemermed.2015.06.034. Epub 2015 Aug 15. PMID: 26281812

9: Colchicine-clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori.

[Cohen Oren,Locketz Garrett,Hershko Alon Y,Gorshtein Alexander,Levy Yair]
Rheumatol Int.2015 Nov;35(11):1937-41. doi: 10.1007/s00296-015-3325-y. Epub 2015 Jul 26. PMID: 26210999

10: Clarithromycin-associated rhabdomyolysis in an infant.

[Mustafa Gulgun,Necati Balamtekin]
J Clin Rheumatol.2014 Dec;20(8):457. doi: 10.1097/RHU.0000000000000192. PMID: 25417692

11: Acute colchicine intoxication complicated with extramedullary hematopoiesis due to filgrastim in a child.

[Kilic Suar C,Alaygut Demet,Unal Ekrem,Koç Elif,Patiroglu Turkan]
J Pediatr Hematol Oncol.2014 Oct;36(7):e460-2. doi: 10.1097/MPH.0000000000000071. PMID: 24309614

12: Colchicine-induced rhabdomyolysis following a concomitant use of clarithromycin in a haemodialysis patient with familial Mediterranean fever.

[Çelebi Zeynep Kendi,Akturk Serkan,Oktay Esen Ismet,Duman Neval,Keven Kenan]
Clin Kidney J.2013 Dec;6(6):665-6. doi: 10.1093/ckj/sft129. PMID: 26120465

13: Characterization of Statin-Associated Myopathy Case Reports in Thailand Using the Health Product Vigilance Center Database.

[Boonmuang Pornwalai,Nathisuwan Surakit,Chaiyakunapruk Nathorn,Suwankesawong Wimon,Pokhagul Pattreya,Teerawattanapong Nattawat,Supsongserm Pairin]
Drug Saf.2013 Sep;36(9):779-87. doi: 10.1007/s40264-013-0055-5. PMID: 23615756

14: Cytochrome P450 drug interactions with statin therapy.

[Goh Ivanna Xin Wei,How Choon How,Tavintharan Subramaniam]
Singapore Med J.2013 Mar;54(3):131-5. PMID: 23546024

15: Colchicine-induced rhabdomyolysis caused by interaction with clarithromycin in a patient with Behcet disease.

[Kim Ji-Beom,Kim Sujeong,Lee Taehoon,Lee Yoon Su,Cho You Sook,Moon Hee-Bom,Kim Yong-Gil,Kim Tae-Bum]
J Clin Rheumatol.2013 Mar;19(2):108-9. doi: 10.1097/RHU.0b013e31828639e0. PMID: 23425672

16: Colchicine-induced rhabdomyolysis caused by interaction with clarithromycin in a patient with Behçet disease.

[Kim Ji-Beom,Kim Sujeong,Yoon Sun-young,Lee Taehoon,Lee Yoon Su,Kwon Hyouk-Soo,Cho You Sook,Moon Hee-Bom,Kim Yong-Gil,Kim Tae-Bum]
J Clin Rheumatol.2012 Dec;18(8):453-4. doi: 10.1097/RHU.0b013e318279304e. PMID: 23211591

17: Severe colchicine intoxication in a renal transplant recipient on cyclosporine.

[Garrouste C,Philipponnet C,Kaysi S,Enache I,Tiple A,Heng A E]
Transplant Proc.2012 Nov;44(9):2851-2. doi: 10.1016/j.transproceed.2012.09.028. PMID: 23146540

18: Colchicine toxicity in end-stage renal disease patients: a case-control study.

[Solak Yalcin,Atalay Huseyin,Biyik Zeynep,Alibasic Hayrudin,Gaipov Abduzhappar,Guney Figen,Kucuk Adem,Tonbul Halil Zeki,Yeksan Mehdi,Turk Suleyman]
Am J Ther.2014 Nov-Dec;21(6):e189-95. doi: 10.1097/MJT.0b013e31825a364a. PMID: 22874645

19: Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin.

[Bouquié Régis,Deslandes Guillaume,Renaud Christian,Dailly Eric,Haloun Alain,Jolliet Pascale]
J Clin Rheumatol.2011 Jan;17(1):28-30. doi: 10.1097/RHU.0b013e3182056042. PMID: 21169852

20: Rhabdomyolysis induced by co-administration of fluvastatin and colchicine.

[Sarullo Filippo M,Americo Luigi,Di Franco Antonino,Di Pasquale Pietro]
Monaldi Arch Chest Dis.2010 Sep;74(3):147-9. PMID: 21110512

21: Multiple organ failure after an overdose of less than 0.4 mg/kg of colchicine: role of coingestants and drugs during intensive care management.

[Montiel Virginie,Huberlant Vincent,Vincent Marie-Françoise,Bonbled Frédéric,Hantson Philippe]
Clin Toxicol (Phila).2010 Oct;48(8):845-8. doi: 10.3109/15563650.2010.509101. Epub 2010 Aug 12. PMID: 20969505

22: Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis.

[McKinnell James,Tayek John A]
J Clin Rheumatol.2009 Sep;15(6):303-5. doi: 10.1097/RHU.0b013e3181bbbcd7. PMID: 19734738

23: Colchicine-induced toxicity in a heart transplant patient with chronic renal failure.

[Eleftheriou Giorgio,Bacis Guiseppe,Fiocchi Roberto,Sebastiano Roberta]
Clin Toxicol (Phila).2008 Nov;46(9):827-30. doi: 10.1080/15563650701779703. PMID: 18608282

24: Severe obstructive sleep apnea after cerivastatin therapy: a case report.

[Ebben Matthew R,Sethi Nitin K,Spielman Arthur J]
J Clin Sleep Med.2008 Jun 15;4(3):255-6. PMID: 18595439

25: Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine.

[Justiniano Maria,Dold Sylvia,Espinoza Luis R]
J Clin Rheumatol.2007 Oct;13(5):266-8. PMID: 17921794

26: Which statin should be used together with colchicine? Clinical experience in three patients with nephrotic syndrome due to AA type amyloidosis.

[Sahin Garip,Korkmaz Cengiz,Yalcin Ahmet Uğur]
Rheumatol Int.2008 Jan;28(3):289-91. Epub 2007 Aug 17. PMID: 17703308

27: Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin.

[Francis Lisa,Bonilla Eduardo,Soforo Ekaterina,Neupane Hom,Nakhla Hassan,Fuller Christine,Perl Andras]
Clin Rheumatol.2008 Jan;27(1):129-31. Epub 2007 Jul 13. PMID: 17628739

28: Colchicine-induced rhabdomyolysis.

[Altman Arie,Szyper-Kravitz Martine,Shoenfeld Yehuda]
Clin Rheumatol.2007 Dec;26(12):2197-2199. doi: 10.1007/s10067-007-0682-2. Epub 2007 Jul 10. PMID: 17619811

29: A complex case of renal amyloidosis with a rare co-occurrence of 2 mutations in separate hereditary periodic fever syndrome-related genes.

[Cigni Alessandro,Ledda Franca,Satta Andrea E]
J Nephrol.2006 Jul-Aug;19(4):543-9. PMID: 17048217

30: Colchicine myoneuropathy: the role of rhabdomyolysis.

[Varughese George I,Varghese Abraham I]
Nephrology (Carlton).2006 Oct;11(5):481-2; author reply 482. PMID: 17014570

31: Rhabdomyolysis in a patient treated with colchicine and atorvastatin.

[Tufan Abdurrahman,Dede Didem Sener,Cavus Safak,Altintas Neriman Defne,Iskit Alper Bektas,Topeli Arzu]
Ann Pharmacother.2006 Jul-Aug;40(7-8):1466-9. Epub 2006 Jun 13. PMID: 16772404

32: Rhabdomyolysis: an evaluation of 475 hospitalized patients.

[Melli Giorgia,Chaudhry Vinay,Cornblath David R]
Medicine (Baltimore).2005 Nov;84(6):377-85. PMID: 16267412

33: [A case report of acute neuromyopathy induced by concomitant use of colchicine and bezafibrate].

[Sugie Masayuki,Kuriki Ayako,Arai Daisuke,Ichikawa Hiroo,Kawamura Mitsuru]
No To Shinkei.2005 Sep;57(9):785-90. PMID: 16248366

34: Acute renal failure associated with an accidental overdose of colchicine.

[Borrás-Blasco J,Enriquez R,Sirvent A E,Amoros F,Navarro-Ruiz A,Reyes A]
Int J Clin Pharmacol Ther.2005 Oct;43(10):480-4. PMID: 16240705

35: Possible colchicine rhabdomyolysis in a fluvastatin-treated patient.

[Atasoyu Enes Murat,Evrenkaya T Rifki,Solmazgul Emrullah]
Ann Pharmacother.2005 Jul-Aug;39(7-8):1368-9. Epub 2005 Jun 14. PMID: 15956236

36: Cytoskeletal myotoxicity from simvastatin and colchicine.

[Baker Steven K,Goodwin Susan,Sur Monalisa,Tarnopolsky Mark A]
Muscle Nerve.2004 Dec;30(6):799-802. PMID: 15389652

37: Case report: fatal poisoning with Colchicum autumnale.

[Brvar Miran,Ploj Tom,Kozelj Gordana,Mozina Martin,Noc Marko,Bunc Matjaz]
Crit Care.2004 Feb;8(1):R56-9. Epub 2004 Jan 2. PMID: 14975056

38: Colchicine-induced rhabdomyolysis in a patient with chronic heart failure.

[Debie Karen,Conraads Viviane,Vrints Christiaan]
Acta Cardiol.2003 Dec;58(6):561-2. PMID: 14713183

39: Colchicine-induced myopathy with myotonia in a patient with chronic renal failure.

[Caglar Kayser,Odabasi Zeki,Safali Mukerrem,Yenicesu Mujdat,Vural Abdulgaffar]
Clin Neurol Neurosurg.2003 Sep;105(4):274-6. PMID: 12954545

40: Colchicine-induced rhabdomyolysis: the whole is greater than the sum of its parts!

[Vasudevan Abu R,Uthamalingam Shanmugham,Kumar Sajal,Tamarin Frank,Brensilver Jeffrey M]
Am J Med.2003 Aug 15;115(3):249. PMID: 12935834

41: Colchicine-induced rhabdomyolysis.

[Phanish Mysore K,Krishnamurthy Suchitra,Bloodworth Lionel L O]
Am J Med.2003 Feb 1;114(2):166-7. PMID: 12586247

42: Rhabdomyolysis associated with gemfibrozil-colchicine therapy.

[Atmaca Hulusi,Sayarlioglu Hayriye,Külah Eyüp,Demircan Nejat,Akpolat Tekin]
Ann Pharmacother.2002 Nov;36(11):1719-21. PMID: 12398566

43: Colchicine-induced rhabdomyolysis.

[Boomershine Kellie H]
Ann Pharmacother.2002 May;36(5):824-6. PMID: 11978160

44: Colchicine induced rhabdomyolysis.

[Chattopadhyay I,Shetty H G,Routledge P A,Jeffery J]
Postgrad Med J.2001 Mar;77(905):191-2. PMID: 11222829

45: [Multi-systemic toxicity of colchicine and renal failure: apropos of a case].

[Rosset L,Descombes E,Fellay G,Regamey C]
Schweiz Med Wochenschr.1998 Dec 5;128(49):1953-7. PMID: 9887475

46: Fatal colchicine overdose: report of a case and review of the literature.

[Milne S T,Meek P D]
Am J Emerg Med.1998 Oct;16(6):603-8. PMID: 9786547

47: Colchicine induced rhabdomyolysis.

[Dawson T M,Starkebaum G]
J Rheumatol.1997 Oct;24(10):2045-6. PMID: 9330953

48: Colchicine toxicity in patients with chronic renal failure.

[Montseny J J,Meyrier A,Gherardi R K]
Nephrol Dial Transplant.1996 Oct;11(10):2055-8. PMID: 8918722

49: [Diarrhea and cytolysis].

[Verdier-Plas M,Buisson M,Lagnoui R,Bannwarth B,Ragnaud J M,Gin H,Aubertin J]
Rev Med Interne.1995;16 Suppl 2:254s-256s. PMID: 7652248

50: [Toxic myopathy with kidney failure as a colchicine side effect ifn familial Mediterranean fever].

[Stefanidis I,Böhm R,Hägel J,Maurin N]
Dtsch Med Wochenschr.1992 Aug 14;117(33):1237-40. PMID: 1499522

51: [Drug-induced rhabdomyolysis].

[Chichmanian R M,Mignot G,Spreux A]
Ann Med Interne (Paris).1991;142(8):587-91. PMID: 1807179

52: Is myopathy in renal transplant patients induced by cyclosporin or colchicine?

[Rumpf K W,Henning H V]
Lancet.1990 Mar 31;335(8692):800-1. PMID: 1969550

Search for drugs: