View More View Less
  • 1 Department of Internal Medicine, Szent Lázár County Hospital, Salgótarján, Hungary
  • | 2 Fresenius MC Dialysis Center, Szent Lázár County Hospital, Salgótarján, Hungary
  • | 3 Intensive Care Unit, Szent Lázár County Hospital, Salgótarján, Hungary
  • | 4 Salgó út 4, H-3100, Salgótarján, Hungary
Restricted access

Abstract

Abstract

Rhabdomyolysis (RML) is a rare and severe adverse effect of simvastatin (SIM). Several risk factors were described to play a role in its pathogenesis, namely age > 65, diabetes mellitus, renal disease, high dose statin therapy, chemicals metabolized by cytochrome P450 3A4 or idiosyncrasia.

Case summary

A 66-year-old man with diabetes, ischaemic heart disease and hypertension, on medication of CYP3A4 substrates amlodipine and alprazolam, maximal daily dose of SIM started for unknown cholesterol level. On the second day dark-brown urine, paraparesis, bile-like vomiting, on the fourth day of treatment total tetraparesis and oliguria characterized RML with acute renal failure. During his hospitalization of one-hundred-six days he underwent fourty-nine dialysis treatments. At the follow-up sixteen months after exmission from hospital, his walking improved to using one stick. His cholesterol level is in the physiological range with no statin therapy.

Conclusions

On account of risk factors listed above this case should have been administered low initial dose of SIM. On developing myalgia or weakness in muscles, treatment must be stopped. In a case of predisposition to RML statin therapy and dosage can only be performed under continuous supervision.

  • [1]. R. Lane M. Phillips 2003 Rhabdomyolysis BMJ 327 115116.

  • [2]. A. Salinas J. Solís L. A. Rico 2007 Severe rhabdomyolysis secondary to simvastatin and acenocoumarol Eur. J. Intern. Med. 18 165.

  • [3]. A. Lasocki B. Vote R. Fassett et al. 2007 Simvastatin-induced rhabdomyolysis following cyclosporine treatment for uveitis Ocul. Immunol. Inflamm. 15 345346.

    • Search Google Scholar
    • Export Citation
  • [4]. S. S. Jacob S. Jacob C. Williams et al. 2005 Simvastatin, fenofibrate, and rhabdomyolysis Diabet. Care 28 1258.

  • [5]. R. Gilad Y. Lampl 1999 Rhabdomyolysis induced by simvastatin and ketoconazole treatment Clin. Neuropharmacol. 22 295297.

  • [6]. B. Ricaurte A. Guirguis H. C. Taylor et al. 2006 Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity Ann. Pharmacother. 40 753757.

    • Search Google Scholar
    • Export Citation
  • [7]. H. Nägele S. Behrens S. Hashagen et al. 2007 Rhabdomyolysis after addition of digitoxin to chronic simvastatin and amiodarone therapy Drug Metabol. Drug Interact. 22 195200.

    • Search Google Scholar
    • Export Citation
  • [8]. J. W. Bielecki C. Schraner V. Briner et al. 1999 Rhabdomyolysis and cholestatic hepatitis under treatment with simvastatin and chlorzoxazone Schweiz. Med. Wochenschr. 129 514518.

    • Search Google Scholar
    • Export Citation
  • [9]. R. Hazin J. Y. Abuzetun M. Suker et al. 2008 Rhabdomyolysis induced by simvastatin-fluconazole combination J. Natl. Med. Assoc. 100 444446.

    • Search Google Scholar
    • Export Citation
  • [10]. D. Schmassmann-Suhijar R. Bullingham R. Gasser et al. 1998 Rhabdomyolysis due to interaction of simvastatin with mibefradil Lancet 351 19291930.

    • Search Google Scholar
    • Export Citation
  • [11]. G. A. Schmidt J. D. Hoehns J. L. Purcell et al. 2007 Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir J. Am. Board Fam. Med. 20 411416.

    • Search Google Scholar
    • Export Citation
  • [12]. E. R. Andreou S. Ledger 2003 Potential drug interaction between simvastatin and danazol causing rhabdomyolysis Can. J. Clin. Pharmacol. 10 172174.

    • Search Google Scholar
    • Export Citation
  • [13]. A. J. Burtenshaw G. Sellors R. Downing 2008 Presumed interaction of fusidic acid with simvastatin Anaesthesia 63 656658.

  • [14]. P. Kotanko W. Kirisits F. Skrabal 2002 Rhabdomyolysis and acute renal graft impairment in a patient treated with simvastatin, tacrolimus, and fusidic acid Nephron 90 234235.

    • Search Google Scholar
    • Export Citation
  • [15]. C. B. Hare M. P. Vu C. Grunfeld et al. 2002 Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death Clin. Infect. Dis. 35 e111e112.

    • Search Google Scholar
    • Export Citation
  • [16]. V. Bhatia 2004 Massive rhabdomyolysis with simvastatin precipitated by amoxicillin J. Postgrad. Med. 50 234235.

  • [17]. N. Kanathur M. G. Mathai R. P. Byrd Jr et al. 2001 Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis Tenn. Med. 94 339341.

    • Search Google Scholar
    • Export Citation
  • [18]. A. Tal M. Rajeshawari W. Isley 1997 Rhabdomyolysis associated with simvastatin-gemfibrozil therapy South Med. J. 90 546547.

  • [19]. M. Z. Skrabal J. A. Stading M. S. Monaghan 2003 Rhabdomyolysis associated with simvastatin-nefazodone therapy South Med. J. 96 10341035.

    • Search Google Scholar
    • Export Citation
  • [20]. A. J. Kahri M. M. Valkonen M. K. Vuoristo et al. 2004 Rhabdomyolysis associated with concomitant use of simvastatin and clarithromycin Ann. Pharmacother. 38 719.

    • Search Google Scholar
    • Export Citation
  • [21]. M. Veeraputhiran M. Sundermeyer 2008 Rhabdomyolysis resulting from pharmacologic interaction between erlotinib and simvastatin Clin. Lung Cancer 9 232234.

    • Search Google Scholar
    • Export Citation
  • [22]. D. V. Vlahakos A. Manginas D. Chilidou et al. 2002 Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine Transplantation 73 19621964.

    • Search Google Scholar
    • Export Citation
  • [23]. J. L. Patier F. Ferrere M. A. Moreno-Cobo et al. 2007 Rhabdomyolysis caused by the association of simvastatin and risperidone Med. Clin. (Barc.) 129 439.

    • Search Google Scholar
    • Export Citation
  • [24]. M. Justiniano S. Dold L. R. Espinoza 2007 Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine J. Clin. Rheumatol. 13 266268.

    • Search Google Scholar
    • Export Citation
  • [25]. G. Campbell U. Jayakumar S. McCracken et al. 2007 A cautionary tale: delayed onset rhabdomyolysis due to erythromycin/simvastatin interaction Age Ageing 36 597.

    • Search Google Scholar
    • Export Citation
  • [26]. J. L. Maxa L. B. Melton C. C. Ogu et al. 2002 Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole Ann. Pharmacother. 36 820823.

    • Search Google Scholar
    • Export Citation
  • [27]. A. Mogyorósi B. Bradley A. Showalter et al. 1999 Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin J. Intern. Med. 246 599602.

    • Search Google Scholar
    • Export Citation
  • [28]. S. Jamil P. Iqbal 2004 Rhabdomyolysis induced by a single dose of a statin Heart 90 e3.

  • [29]. I. D. Cockshott 2004 Bicalutamide: clinical pharmacokinetics and metabolism Clin. Pharmacokinet. 43 855678.

  • [30]. L. Wang L. J. Christopher D. Cui et al. 2008 Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics Drug Metab. Dispos. 36 18281839.

    • Search Google Scholar
    • Export Citation
  • [31]. J. van Harten 1995 Overview of the pharmacokinetics of fluvoxamine Clin. Pharmacokinet. 29 Suppl.1 19.

  • [32]. V. A. Eagling D. J. Back M. G. Barry 1997 Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir Br. J. Clin. Pharmacol. 44 190194.

    • Search Google Scholar
    • Export Citation
  • [33]. L. Youlten 2004 The effect of repeat dosing with cimetidine on the pharmacokinetics of intravenous granisetron in healthy volunteers J. Pharm. Pharmacol. 56 169175.

    • Search Google Scholar
    • Export Citation
  • [34]. H. L. Lin U. M. Kent P. F. Hollenberg 2002 Mechanism-based inactivation of cytochrome P450 3A4 by 17 alpha-ethynylestradiol: evidence for heme destruction and covalent binding to protein J. Pharmacol. Exp. Ther. 301 160167.

    • Search Google Scholar
    • Export Citation
  • [35]. T. Uno N. Yasui-Furukori 2006 Effect of grapefruit juice in relation to human pharmacokinetic study Curr. Clin. Pharmacol. 1 157161.

    • Search Google Scholar
    • Export Citation
  • [36]. R. A. McLellan R. K. Drobitch H. McLellan et al. 1995 Norfloxacin interferes with cyclosporine disposition in pediatric patients undergoing renal transplantation Clin. Pharmacol. Ther. 58 322327.

    • Search Google Scholar
    • Export Citation
  • [37]. D. J. Graham J. A. Staffa D. Shatin et al. 2004 Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs JAMA 292 25852590.

    • Search Google Scholar
    • Export Citation
  • [38]. P. Gervois I. P. Torra J. C. Fruchart et al. 2000 Regulation of lipid and lipoprotein metabolism by PPAR activators Clin. Chem. Lab. Med. 38 311.

    • Search Google Scholar
    • Export Citation
  • [39]. K. Morimura C. Cheung J. M. Ward et al. 2006 Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis Carcinogenesis 27 10741080.

    • Search Google Scholar
    • Export Citation
  • [40]. J. Mátyus T. Király I. Kárpáti et al. 2001 Fibrát okozta súlyos rhabdomyolysis idült veseelégtelen betegekben Magy. Belorv. Arch. 54 3134 (Severe rhabdomyolysis caused by fibrates in patients with chronic renal insufficiency.).

    • Search Google Scholar
    • Export Citation
  • [41]. J. Sacher L. Weigl M. Werner et al. 2005 Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells JPET 314 10321041.

    • Search Google Scholar
    • Export Citation
  • [42]. I. Kárpáti 2004 Rhabdomyolysis és az akut veseelégtelenség Gy. Kakuk Klinikai nephrologia Medicina Budapest (Rhabdomyolysis and acute renal insufficiency.).

    • Search Google Scholar
    • Export Citation
  • [43]. S. Schech D. Graham J. Staffa 2007 Risk factors for statin-associated rhabdomyolysis Pharmacoepidemiol. Drug Saf. 16 352358.

  • [44]. H. B. Brewer 2003 Benefit-risk assessment of Rosuvastatin 10 to 40 milligrams Am. J. Cardiol. 92 Suppl. 23K29K.

  • [45]. D. N. Kiortsis T. D. Filippatos D. P. Mikhailidis 2007 Statin-associated adverse effects beyond muscle and liver toxicity Atherosclerosis 195 716.

    • Search Google Scholar
    • Export Citation
  • [46]. J. R. Modi M. S. Cratty 2002 Fluvastatin-induced rhabdomyolysis Ann. Pharmacother. 36 18701874.

  • [47]. L. A. García-Rodríguez A. González-Pérez M. R. Stang et al. 2008 The safety of rosuvastatin in comparison with other statins in over 25 000 statin users in the Saskatchewan Health Databases Pharmacoepidemiol. Drug Saf. 17 953961.

    • Search Google Scholar
    • Export Citation
  • [48]. K. Yokote H. Bujo H. Hanaoka et al. 2008 Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients. Collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study) Atherosclerosis 201 345352.

    • Search Google Scholar
    • Export Citation
  • [49]. K. J. Ronaldson J. M. O'shea I.W. Boyd 2006 Risk factors for rhabdomyolysis with simvastatin and atorvastatin Drug Saf. 29 10611067.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 3 3 0
Full Text Views 12 4 0
PDF Downloads 0 0 0