Skip to main content
Top
Published in: Drug Safety 11/2006

01-11-2006 | Short Communication

Risk Factors for Rhabdomyolysis with Simvastatin and Atorvastatin

Authors: Dr Kathlyn J. Ronaldson, Justine M. O’Shea, Ian W. Boyd

Published in: Drug Safety | Issue 11/2006

Login to get access

Abstract

Objective: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC).
Design: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age ≥70 years, dose ≥40mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications.
Results: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin.
A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor (‘statin’) doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin.
Conclusion: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.
Literature
1.
go back to reference Pharmaceutical Pricing Section, Pharmaceutical Benefits Branch, Ministry of Health and Ageing, Government of Australia. Expenditure and prescriptions twelve months to 30 June 2005 [online]. Available from URL: http://www.health.gov.au/internet/wcms/publishing.nsf/ Content/pbs-stats-pbexp-jun05-index [ccessed 2006Jan 30] Pharmaceutical Pricing Section, Pharmaceutical Benefits Branch, Ministry of Health and Ageing, Government of Australia. Expenditure and prescriptions twelve months to 30 June 2005 [online]. Available from URL: http://​www.​health.​gov.​au/​internet/​wcms/​publishing.​nsf/​ Content/pbs-stats-pbexp-jun05-index [ccessed 2006Jan 30]
2.
go back to reference Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22CrossRef Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22CrossRef
3.
go back to reference Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–96CrossRefPubMed Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–96CrossRefPubMed
4.
go back to reference 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: 1495–504CrossRefPubMed 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: 1495–504CrossRefPubMed
5.
go back to reference Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002; 36: 288–95CrossRefPubMed Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002; 36: 288–95CrossRefPubMed
7.
go back to reference Ballantyne CM, Corsini A, Davidson MH, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003; 163: 553–64CrossRefPubMed Ballantyne CM, Corsini A, Davidson MH, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003; 163: 553–64CrossRefPubMed
8.
go back to reference McKelvie PA, Dennett X. Myopathy associated with HMG-CoA reductase inhibitors (statins): a series of 10 patients and review of the literature. J Clin Neuromuscular Dis 2002; 3: 143–8CrossRef McKelvie PA, Dennett X. Myopathy associated with HMG-CoA reductase inhibitors (statins): a series of 10 patients and review of the literature. J Clin Neuromuscular Dis 2002; 3: 143–8CrossRef
9.
go back to reference Huynh T, Cordato D, Yang F, et al. HMG CoA reductase-inhibitor-related myopathy and the influence of drug interactions. Intern Med J 2002; 32: 486–90CrossRefPubMed Huynh T, Cordato D, Yang F, et al. HMG CoA reductase-inhibitor-related myopathy and the influence of drug interactions. Intern Med J 2002; 32: 486–90CrossRefPubMed
10.
go back to reference Zocor (simvastatin) [Australian Product Information]. Granville, NSW: Merck Sharpe & Dohme (Aust.) Pty Ltd, 2005 May 26 Zocor (simvastatin) [Australian Product Information]. Granville, NSW: Merck Sharpe & Dohme (Aust.) Pty Ltd, 2005 May 26
11.
go back to reference Lipitor (atorvastatin) [Australian Product Information]. West Ryde, NSW: Pfizer Australia Pty Ltd, 2005 Mar 29 Lipitor (atorvastatin) [Australian Product Information]. West Ryde, NSW: Pfizer Australia Pty Ltd, 2005 Mar 29
12.
go back to reference Fusidin (fusidic acid) [Australian Product Information]. Parkville, VIC: CSL Limited, 2005 Dec 8 Fusidin (fusidic acid) [Australian Product Information]. Parkville, VIC: CSL Limited, 2005 Dec 8
13.
go back to reference Krum H, McNeil JJ. The short life and rapid death of a novel antihypertensive and antianginal agent. Med J Aust 1998; 169: 408–9PubMed Krum H, McNeil JJ. The short life and rapid death of a novel antihypertensive and antianginal agent. Med J Aust 1998; 169: 408–9PubMed
14.
go back to reference Tateishi T, Soucek P, Caraco Y, et al. Colchicine biotransformation by human liver microsomes: identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol 1997; 53: 111–6CrossRefPubMed Tateishi T, Soucek P, Caraco Y, et al. Colchicine biotransformation by human liver microsomes: identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol 1997; 53: 111–6CrossRefPubMed
15.
go back to reference Mirghani RA, Hellgren U, Bertilsson L, et al. Metabolism and elimination of quinine in healthy volunteers. Eur J Clin Pharmacol 2003; 59: 423–7CrossRefPubMed Mirghani RA, Hellgren U, Bertilsson L, et al. Metabolism and elimination of quinine in healthy volunteers. Eur J Clin Pharmacol 2003; 59: 423–7CrossRefPubMed
16.
go back to reference Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine 2005; 84: 377–85CrossRefPubMed Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine 2005; 84: 377–85CrossRefPubMed
17.
18.
go back to reference Sipe BE, Jones RJ, Bokhart GH. Rhabdomyolysis causing AV blockade due to possible atorvastatin, esomeprazole, and clarithromycin interaction. Ann Pharmacother 2003; 37: 808–11CrossRefPubMed Sipe BE, Jones RJ, Bokhart GH. Rhabdomyolysis causing AV blockade due to possible atorvastatin, esomeprazole, and clarithromycin interaction. Ann Pharmacother 2003; 37: 808–11CrossRefPubMed
19.
go back to reference Canadian Adverse Reaction Newsletter. Clopidogrel (Plavix): suspected drug interaction with atorvastatin (Lipitor) and cyclosporine resulting in rhabdomyolysis [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v15n2_e.html [Accessed 2006 Sep 19] Canadian Adverse Reaction Newsletter. Clopidogrel (Plavix): suspected drug interaction with atorvastatin (Lipitor) and cyclosporine resulting in rhabdomyolysis [online]. Available from URL: http://​www.​hc-sc.​gc.​ca/​dhp-mps/​medeff/​bulletin/​carn-bcei_​v15n2_​e.​html [Accessed 2006 Sep 19]
20.
go back to reference Mogyorósi A, Bradley B, Showalter A, et al. Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. J Intern Med 1999; 246: 599–602CrossRefPubMed Mogyorósi A, Bradley B, Showalter A, et al. Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. J Intern Med 1999; 246: 599–602CrossRefPubMed
21.
go back to reference Wicki J, Rutschmann OT, Burri H, et al. Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia possibly complicated by clozapine. Ann Pharmacother 1998; 32: 892–5CrossRefPubMed Wicki J, Rutschmann OT, Burri H, et al. Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia possibly complicated by clozapine. Ann Pharmacother 1998; 32: 892–5CrossRefPubMed
22.
go back to reference Rätz Bravo AE, Tchambaz L, Krähenbühl-Melcher A, et al. Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Drug Saf 2005; 28: 263–75CrossRefPubMed Rätz Bravo AE, Tchambaz L, Krähenbühl-Melcher A, et al. Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Drug Saf 2005; 28: 263–75CrossRefPubMed
23.
go back to reference Pharmaceutical Benefits Scheme, Medicare Australia [online]. Available from URL: http://www.medicareaustralia.gov.au/statistics/dyn_pbs/forms/pbs_tab1.shtml [Accessed 2006 Jan 31] Pharmaceutical Benefits Scheme, Medicare Australia [online]. Available from URL: http://​www.​medicareaustrali​a.​gov.​au/​statistics/​dyn_​pbs/​forms/​pbs_​tab1.​shtml [Accessed 2006 Jan 31]
24.
go back to reference Gaist D, García Rodríguez LA, Huerta C, et al. Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. Epidemiology 2001; 12: 565–9CrossRefPubMed Gaist D, García Rodríguez LA, Huerta C, et al. Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. Epidemiology 2001; 12: 565–9CrossRefPubMed
25.
go back to reference Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 2585–90CrossRefPubMed Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 2585–90CrossRefPubMed
26.
go back to reference Cziraky MJ, Willey MJ, McKenney JM, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol 2006; Suppl. 97: 61C–8CCrossRef Cziraky MJ, Willey MJ, McKenney JM, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol 2006; Suppl. 97: 61C–8CCrossRef
27.
go back to reference de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes. JAMA 2004; 292: 1307–16CrossRefPubMed de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes. JAMA 2004; 292: 1307–16CrossRefPubMed
28.
go back to reference Krasuski RA, Doeppenschmidt D, Henry JS, et al. Conversion to atorvastatin in patients intolerant or refractory to simvastatin therapy: The CAPISH Study. Mayo Clin Proc 2005; 80: 1163–8CrossRefPubMed Krasuski RA, Doeppenschmidt D, Henry JS, et al. Conversion to atorvastatin in patients intolerant or refractory to simvastatin therapy: The CAPISH Study. Mayo Clin Proc 2005; 80: 1163–8CrossRefPubMed
Metadata
Title
Risk Factors for Rhabdomyolysis with Simvastatin and Atorvastatin
Authors
Dr Kathlyn J. Ronaldson
Justine M. O’Shea
Ian W. Boyd
Publication date
01-11-2006
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 11/2006
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200629110-00005

Other articles of this Issue 11/2006

Drug Safety 11/2006 Go to the issue

Review Article

Betahistine