Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin

Abstract

Abstract. Mogyoro Âsi A, Bradley B, Showalter A, Schubert ML (Medical College of Virginia/Virginia Commonwealth University and Hunter Holmes McGuire VAMC, Richmond, Virginia, USA). Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin (Case Report). J Intern Med 1999; 246: 599±602.Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is widely used to treat hyperlipidaemia. Although myalgias are recognized adverse effects, clinically significant elevations in serum creatine phosphokinase (CPK) levels are uncommon. We describe a case of rhabdomyolysis and acute renal failure associated with concomitant use of simvastatin and warfarin. Rhabdomyolysis and renal failure occurred 7 days after warfarin (5 mg day 21 ) was added to a chronic stable dose of simvastatin (20 mg day 21 ) and resolved abruptly after discontinuation of simvastatin. We recommend careful monitoring when warfarin is given to patients receiving simvastatin.

Potential drug interactions with statins: Estonian register-based study

“…Previous studies showed that a combination of simvastatin with fibrates, cyclosporine, digoxin, macrolide antibiotics, warfarin or azoles increased the risk of statin- mediated rhabdomyolysis [9,22,23]. Therefore, in our study, 10% of simvastatin users (4.3% of all statin users) are at a risk of developing rhabdomyolysis.…”

“…Here, the cost of the medicines may have been the reason for the change – more expensive medicines were replaced with cheaper analogues without consideration of the potential risks due to drug interactions, which may become clinically significant, especially in the older population and in particular, in the case of polypharmacy [10, 22]. …”

Drug–drug interactions that interfere with statin metabolism

“…However, the potentiating effect of warfarin on statin levels has not yet been studied in sufficient detail [79]. Pitavastatin and rosuvastatin are known to be weakly metabolized by CYP2C9 [80].…”

Fibrat-/Statin-Myopathie

“…Bisher wurden keine muskulären Nebenwirkungen, insbesondere keine CK-Erhöhung oder Rhabdomyolyse beschrieben [17,23,25]. [63], Diltiazem [65], Gemfibrozil [57,59], Mibefradil [72], Nefazodon [73], Pravastatin, Sildenefil [77], Troglitazone [78] oder Warfarin [79] Rhabdomyolysen beschrieben (Tabelle 3). Die Kombination Simvastatin mit Ezetimibe wurde von 40 Patienten ohne muskuläre Nebenwirkungen vertragen [8].…”