Does simvastatin cause more myotoxicity compared with other statins?

Annals of Pharmacotherapy

Volumn 43, Issue 12, 2009, Pages 2012-2020

  Backes, James M ^a   Howard, Patricia A ^b   Ruisinger, Janelle F ^a   Moriarty, Patrick M ^a  

^a UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

Drug interactions; Myopathy; Rhabdomyolysis; Statins

Indexed keywords

AMIODARONE; ATORVASTATIN; CERIVASTATIN; CLARITHROMYCIN; CYCLOSPORIN; CYTOCHROME P450; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; CYTOCHROME P450 INHIBITOR; DANAZOL; ENZYME INHIBITOR; ERYTHROMYCIN; FIBRIC ACID DERIVATIVE; FLUINDOSTATIN; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ITRACONAZOLE; KETOCONAZOLE; MACROLIDE; MEVINOLIN; NEFAZODONE; PRAVASTATIN; PROTEINASE INHIBITOR; PYRROLE DERIVATIVE; ROSUVASTATIN; SIMVASTATIN; TELITHROMYCIN; VERAPAMIL;

CLINICAL TRIAL; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDUCED DISEASE; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG WITHDRAWAL; ENZYME INHIBITION; EVENING DOSAGE; FOOD DRUG INTERACTION; GLUCURONIDATION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; INCIDENCE; LOW DRUG DOSE; MAXIMUM PERMISSIBLE DOSE; MUSCLE DISEASE; MYALGIA; MYOPATHY; PRACTICE GUIDELINE; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; RHABDOMYOLYSIS; RISK FACTOR; SIDE EFFECT; UNSPECIFIED SIDE EFFECT; WEAKNESS;

CLINICAL TRIALS AS TOPIC; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; DYSLIPIDEMIAS; ENZYME INHIBITORS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MUSCULAR DISEASES; RHABDOMYOLYSIS; RISK FACTORS; SIMVASTATIN;

EID: 72249115539     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1M410     Document Type: Review

References (73)

1. Mitka M. Expanding statin use to help more at-risk patients is causing financial heartburn. JAMA 2003;290:2243-2245 (Pubitemid 37430551)
2. Hsu I, Spinler SA, Johnson NE. Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Ann Pharmacother 1995;29:743-759
3. Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients - the PRIMO study. Cardiovasc Drugs Ther 2005;19:403-414 (Pubitemid 43228152)
4. Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol 2002;40:567-572 (Pubitemid 34833176)
5. Davidson MH. Combination therapy for dyslipidemia: safety and regulatory considerations. Am J Cardiol 2002;90:50-60.
6. Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol 1997;79:38-42.
7. Rosenson RS, Bays HE. Results of two clinical trials on the safety and efficacy of pravastatin 80 and 160 mg per day. Am J Cardiol 2003;91:878-881
8. Jacobson TA. Statin safety: lessons from new drug applications for marketed statins. Am J Cardiol 2006;97:44C-51C.
9. Omar MA, Wilson JP, Cox TS. Rhabdomyolysis and HMG-CoA reductase inhibitors. Ann Pharmacother 2001;35:1096-1107 DOI 10.1345/aph.10228
10. Bottorff MB. Statin safety and drug interactions: clinical implications. Am J Cardiol 2006;97:27C-31C.
11. Nissen SE. High-dose statins in acute coronary syndromes: not just lipid levels. JAMA 2004;292:1365-1367 (Pubitemid 39223231)
12. Mitka M. Researchers worry about myopathy risk for patients taking high-dose simvastatin. JAMA 2009;301:261-262
13. Package insert labeling change - concomitant use with 3A4 inhibitors. 2002. www.accessdata.fda.gov/drugsatfda-docs/appletter/2002/19766s51ltr.pdf (accessed 2009 Jul 2).
14. FDA MedWatch safety alert August 2008 - simvastatin used with amiodarone. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlerts forHumanMedicalProducts/ucm095009.htm (accessed 2009 Jul 2).
15. Robinson JG. Simvastatin: present and future perspectives. Exp Opin Pharmacother 2007;8:2159-2172
16. Neuvonen PJ, Kantola T, Kivisto KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998;63:332-341 (Pubitemid 28182231)
17. Kantola T, Kivisto KT, Neuvonen PJ. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 1998;64:177-182 (Pubitemid 28423853)
18. Neuvonen PJ, Jalava KM. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996;60:54-61.
19. Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998;64:58-65.
20. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-581 (Pubitemid 44908269)
21. Jacobson TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 2004;94:1140-1146
22. Kivisto KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998;46:49-53. (Pubitemid 28308424)
23. Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000; 68:391-400. (Pubitemid 30803528)
24. Cooper KJ, Martin PD, Dane AL, Warwick MJ, Schneck DW, Cantarini MV. Effect of itraconazole on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2003;73:322-329
25. Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on cerivastatin pharmacokinetics. Eur J Clin Pharmacol 1999;54:851-855
26. Amsden GW, Kuye O, Wei GC. A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers. J Clin Pharmacol 2002;42:444-449 (Pubitemid 34259779)
27. Siedlik PH, Olson SC, Yang BB, Stern RH. Erythromycin coadministration increases plasma atorvastatin concentrations. J Clin Pharmacol 1999;39:501-504
28. Muck W, Ochmann K, Rohde G, Unger S, Kuhlmann J. Influence of erythromycin pre- and co-treatment on single-dose pharmacokinetics of the HMG-CoA reductase inhibitor cerivastatin. Eur J Clin Pharmacol 1998;53:469-473 (Pubitemid 28154748)
29. Cooper KJ, Martin PD, Dane AL, Warwick MJ, Raza A, Schneck DW. The effect of erythromycin on the pharmacokinetics of rosuvastatin. Eur J Clin Pharmacol 2003;59:51-56
30. Hermann M, Asberg A, Christensen H, Holdaas H, Hartmann A, Reubsaet JL. Substantially elevated levels of atorvastatin and metabolites in cyclosporine-treated renal transplant recipients. Clin Pharmacol Ther 2004;76:388-391 (Pubitemid 39313130)
31. Regazzi MB, Iacona I, Campana C, et al. Altered disposition of pravastatin following concomitant drug therapy with cyclosporin A in transplant recipients. Transplant Proc 1993;25:2732-2734 (Pubitemid 23239614)
32. Hedman M, Neuvonen PJ, Neuvonen M, Holmberg C, Antikainen M. Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression. Clin Pharmacol Ther 2004;75:101-109 (Pubitemid 38130122)
33. Asberg A. Interactions between cyclosporin and lipid-lowering drugs: implications for organ transplant recipients. Drugs 2003;63:367-378 (Pubitemid 36259524)
34. Simonson SG, Raza A, Martin PD, et al. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clin Pharmacol Ther 2004;76:167-177 (Pubitemid 39013406)
35. Arnadottir M, Eriksson LO, Thysell H, Karkas JD. Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Nephron 1993;65:410-413 (Pubitemid 23321239)
36. Ichimaru N, Takahara S, Kokado Y, et al. Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus. Atherosclerosis 2001;158:417-423 (Pubitemid 32913652)
37. Park JW, Siekmeier R, Lattke P, et al. Pharmacokinetics and pharmacodynamics of fluvastatin in heart transplant recipients taking cyclosporine A. J Cardiovasc Pharmacol Ther 2001;6:351-361 (Pubitemid 34141820)
38. Muck W, Mai I, Fritsche L, et al. Increase in cerivastatin systemic exposure after single and multiple dosing in cyclosporine-treated kidney transplant recipients. Clin Pharmacol Ther 1999;65:251-261 (Pubitemid 29142931)
39. Backman JT, Kyrklund C, Kivisto KT, Wang JS, Neuvonen PJ. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000;68:122-129 (Pubitemid 30659167)
40. Kyrklund C, Backman JT, Kivisto KT, Neuvonen M, Laitila J, Neuvonen PJ. Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Clin Pharmacol Ther 2001;69:340-345 (Pubitemid 32477075)
41. Schneck DW, Birmingham BK, Zalikowski JA, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2004;75:455-463
42. Prueksaritanont T, Gorham LM, Ma B, et al. In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 1997;25:1191-1199
43. Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther 2003;73:538-544 (Pubitemid 37249124)
44. Backman JT, Luurila H, Neuvonen M, Neuvonen PJ. Rifampin markedly decreases and gemfibrozil increases the plasma concentrations of atorvastatin and its metabolites. Clin Pharmacol Ther 2005;78:154-167 (Pubitemid 41112284)
45. Spence JD, Munoz CE, Hendricks L, Latchinian L, Khouri HE. Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol 1995;76:80A-3A.
46. Black C, Jick H. Etiology and frequency of rhabdomyolysis. Pharmacotherapy 2002;22:1524-1526
47. Matsuzawa Y, Kita T, Mabuchi H, et al. Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients. Circ J 2003;67:287-294
48. Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004;292:2585-2590 (Pubitemid 39577514)
49. Cziraky MJ, Willey VJ, McKenney JM, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol 2006;97:61C-8C.
50. Bays H. Statin safety: an overview and assessment of the data - 2005. Am J Cardiol 2006;97:6C-26C.
51. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol 2006;97:52C-60C.
52. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435 (Pubitemid 40471450)
53. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294:2437-2445 (Pubitemid 41627921)
54. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-2207
55. SEARCH Study Collaborative Group, Bowman L, Armitage J, Bulbulia R, Parish S, Collins R. Study of the effectiveness of additional reductions in cholesterol and homocysteine. American Heart Association Scientific Sessions. New Orleans, LA, 2008.
56. Serruys PW, de Feyter P, Macaya C, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;287:3215-3222 (Pubitemid 34686102)
57. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004;292:1307-1316
58. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-559
59. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504 (Pubitemid 38477774)
60. Product information. Zocor (simvastatin). Whitehouse Station, NJ: Merck and Co., June 2008.
61. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002;346:539-540
62. Product information. Zocor (simvastatin). Whitehouse Station, NJ: Merck and Co., June 2002.
63. Becquemont L, Neuvonen M, Verstuyft C, et al. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther 2007;81:679-684 (Pubitemid 46625102)
64. Chouhan UM, Chakrabarti S, Millward LJ. Simvastatin interaction with clarithromycin and amiodarone causing myositis (letter). Ann Pharmacother 2005;39:1760-1761 Epub 13 Sept 2005. DOI 10.1345/aph.1G195 (Pubitemid 41393145)
65. Nagele H, Behrens S, Hashagen S, Azizi M. Rhabdomyolysis after addition of digitoxin to chronic simvastatin and amiodarone therapy. Drug Metabol Drug Interact 2007;22:195-200. (Pubitemid 47215873)
66. Ricaurte B, Guirguis A, Taylor HC, Zabriskie D. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother 2006;40:753-757 Epub 14 Mar 2006. DOI 10.1345/aph.1G462
67. Roten L, Schoenenberger RA, Krähenbühl S, Schlienger RG. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother 2004;38:978-981 Epub 6 Apr 2004. DOI 10.1345/aph.1D498
68. Saliba WR, Elias M. Myopathy from the combination of simvastatin and amiodarone (letter). Eur J Intern Med 2006;17:148. (Pubitemid 43265873)
69. Schmidt GA, Hoehns JD, Purcell JL, Friedman RL, Elhawi Y. Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir. J Am Board Fam Med 2007;20:411-416 (Pubitemid 47173856)
70. Wratchford P, Ponte CD. High-dose simvastatin and rhabdomyolysis. Am J Health Syst Pharm 2003;60:698-700.
71. Merck Sharp Dohme - licensed medications in the United Kingdom. http://emc.medicines.org.uk/document.aspx?documentId=1201 (accessed 2009 Jul 2).
72. FDA approval letter - simvastatin 80 mg dose, 1998. www.accessdata.fda. gov/drugsatfda-docs/appletter/1998/19766s026s028.pdf (accessed 2009 Jul 2).
73. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239 [Erratum in Circulation 2004;110:763].