Basic Information
ID DDInter133 and DDInter431
Interaction Coadministration of colchicine and HMG-CoA reductase inhibitors may increase the risk of myopathy due to a combination of pharmacodynamic and pharmacokinetic effects. These agents are individually myotoxic and may have additive or synergistic effects when used together. In addition, colchicine and some HMG-CoA reductase inhibitors are substrates of the CYP450 3A4 isoenzyme and P-glycoprotein efflux transporter, thus competitive inhibition may occur resulting in increased drug absorption and decreased excretion.
Management Extreme caution is advised if colchicine is used in combination with HMG-CoA reductase inhibitors, particularly in the elderly and patients with underlying renal or hepatic impairment. Some experts recommend checking the creatine kinase level a week or two after coadministration of these agents and after any dose increase, although such monitoring does not reliably prevent the occurrence of severe myopathy. Patients should be advised to contact their physician if they experience symptoms of toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paraesthesia, and numbness. The drugs should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.
References [1] "Colchicine: serious interactions." Prescrire Int 17 (2008): 151-3 [2] 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) 48 (2010): 845-8 [3] Wilbur K, Makowsky M "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy 24 (2004): 1784-92 [4] Hsu WC, Chen WH, Chang MT, Chiu HC "Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin." Clin Neuropharmacol 25 (2002): 266-8 [5] Justiniano M, Dold S, Espinoza LR "Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine." J Clin Rheumatol 13 (2007): 266-8 [6] Alayli G, Cengiz K, Canturk F, Durmus D, Akyol Y, Menekse EB "Acute myopathy in a patient with concomitant use of pravastatin and colchicine." Ann Pharmacother 39 (2005): 1358-61 [7] Tufan A, Dede DS, Cavus S, Altintas ND, Iskit AB, Topeli A "Rhabdomyolysis in a patient treated with colchicine and atorvastatin." Ann Pharmacother 40 (2006): 1466-9 [8] Francis L, Bonilla E, Soforo E, et al. "Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin." Clin Rheumatol 27 (2008): 129-31 [9] Atasoyu EM, Evrenkaya TR, Solmazgul E "Possible colchicine rhabdomyolysis in a fluvastatin-treated patient." Ann Pharmacother 39 (2005): 1368-9 [10] "Product Information. Colcrys (colchicine)." AR Scientific Inc, Philadelphia, PA. [11] Goldbart A, Press J, Sofer S, Kapelushnik J "Near fatal acute colchicine intoxication in a child. A case report." Eur J Pediatr 159 (2000): 895-7 [12] Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K "Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure." J Nephrol 19 (2006): 515-7 [13] Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C "Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration." Clin Nephrol 55 (2001): 181-2 [14] Cheng VC, Ho PL, Yuen KY "Two probable cases of serious drug interaction between clarithromycin and colchicine." South Med J 98 (2005): 811-3 [15] McKinnell J, Tayek JA "Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis." J Clin Rheumatol 15 (2009): 303-5 [16] Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E "Acute colchicine intoxication: possible role of erythromycin administration." J Rheumatol 19 (1992): 494-6 [17] Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P "Acute colchicine intoxication during clarithromycin administration." Ann Pharmacother 38 (2004): 2074-7 [18] Wilbur K, Makowsky M "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy 24 (2004): 1784-92 [19] Schiff D, Drislane FW "Rapid-onset colchicine myoneuropathy." Arthritis Rheum 35 (1992): 1535-6 [20] Boomershine KH "Colchicine-induced rhabdomyolysis." Ann Pharmacother 36 (2002): 824-6 [21] van der Velden W, Huussen J, Ter Laak H, de Sevaux R "Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin." Neth J Med 66 (2008): 204-6 [22] Hung IF, Wu AK, Cheng VC, et al. "Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study." Clin Infect Dis 41 (2005): 291-300 [23] Pettinger WA "Clonidine, a new antihypertensive drug." N Engl J Med 293 (1975): 1179-80 [24] Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ "Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation." Biochem Pharmacol 53 (1996): 111-6 [25] Dahan A, Amidon GL "Grapefruit juice and its constitueants augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein." Pharm Res 26 (2009): 883-92 [26] "Colchicine: serious interactions." Prescrire Int 17 (2008): 151-3 [27] Putterman C, Ben-Chetrit E, Caraco Y, Levy M "Colchicine intoxication: clinical pharmacology, risk factors, features, and management." Semin Arthritis Rheum 21 (1991): 143-55 [28] "Product Information. Colcrys (colchicine)." AR Scientific Inc, Philadelphia, PA. [29] "Severe colchicine-macrolide interactions." Prescrire Int 12 (2003): 18-9 [30] Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706 [31] Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83 [32] Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402 [33] "Product Information. Mevacor (lovastatin)." Merck & Co, Inc, West Point, PA. [34] Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10 [35] Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74 [36] Thompson PD, Clarkson P, Karas RH "Statin-associated myopathy." JAMA 289 (2003): 1681-90 [37] "Product Information. Zocor (simvastatin)." Merck & Co, Inc, West Point, PA.
Alternative for Atorvastatin C10B
Amlodipine Niacin Valsartan Perindopril Acetylsalicylic acid Indapamide
Ramipril Lisinopril Ezetimibe Bempedoic acid

C10A
Colestipol
More
Alternative for Colchicine M04A
Pegloticase Febuxostat Rasburicase Lesinurad
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.