Rhabdomyolysis simvastatin

Simvastatin Rhabdomyolysis occurred in a 77-year-old woman taking simvastatin 40 mg/day when she also took ciprofloxacin for a urinary tract infection [53 ]. The symptoms began after the second dose of ciprofloxacin, and 3 days later the creatine kinase activity was 28 980 U/1. After withdrawal of ciprofloxacin and simvastatin, the creatine kinase activity returned to normal within 14 days and functional activity improved by day 23. The author speculated that simvastatin toxicity had been caused by the addition of ciprofloxacin, although the mechanism is unclear, as ciprofloxacin is only a weak inhibitor of CYP3A4, of which simvastatin is a substrate. 

Simvastatin Rhabdomyolysis after combined therapy with simvastatin 80 mg/day and clarithromycin has been recently reported in two women they recovered rapidly, after simvastatin withdrawal [13T, 132 ]. The interacting mechanism was probably inhibition of CYP3A4 inhibition of P glycoprotein transport of simvastatin may also have contributed. 

Lovastatin, simvastatin Ketoconazole, erythromycin, etc. CYP3A4 Rhabdomyolysis... 

Baycol (cerivastatin, sold as Lipobay in Europe, Bayer) is a statin, a class of cholesterol-lower drugs. Statins are the most prescribed drugs in the United States, with more than 12 million people taking them, and more than 700,000 people in the United States taking cerivastatin. It received marketing approval on June 26, 1997 and was voluntarily removed from the market on August 8, 2001 because of its link to 100 deaths and several injuries from potentially the muscle disease rhabdomyolysis. The other statins — lovas-tatin (Mevacor Merck) pravastatin (Pravachol Bristol-Myers Squibb) simvastatin (Zocor Merck) fluvastatin (Lescol Novartis) atorvastatin (Lipitor Parke-Davis) rosuvastatin... 

Tipranavir both inhibits and induces the CYP3A4 system. When used in combination with ritonavir, its net effect is inhibition. Tipranavir also induces P-glycoprotein transporter and thus may alter the disposition of many other drugs (Table 49-4). Concurrent administration of tipranavir with fosamprenavir or saquinavir should be avoided owing to decreased blood levels of the latter drugs. Tipranavir/ritonavir may also decrease serum levels of valproic acid and omeprazole. Levels of lovastatin, simvastatin, atorvastatin, and rosuvastatin may be increased, increasing the risk for rhabdomyolysis and myopathy. 

Simvastatin [NE] Myopathy and rhabdomyolysis noted in patients taking sim-vastatin and cyclosporine. 

Jacobson RH, Wang P, Glueck CJ. Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone. JAMA 1997 277(4) 296-7. 

A 59-year-old woman taking pravastatin 20 mg/day tolerated immunosuppression with ciclosporin, prednisone, and mycophenolate mofetil for 4 years after heart transplantation. After switching from pravastatin to simvastatin she developed severe muscle weakness and laboratory evidence of muscle breakdown. The biochemical markers of rhabdomyolysis did not normalize until after repeat hemodialysis. Clinical improvement did not occur until after 5 months. 

The incidence of rhabdomyolysis in patients taking different statins and fibrates, alone and in combination, has been estimated using data from 11 managed health care plans across the USA (43). The incidences of rhabdomyolysis were 0.44 per 10 000 person-years of treatment with atorvastatin, pravastatin, or simvastatin, 5.34 with cerivastatin, and 2.82 with fibrates. The incidence increased to 5.98 when atorvastatin, pravastatin, or simvastatin was with a fibrate, and to 1035 when cerivastatin was combined with a fibrate. 

Simvastatin 5 mg/day caused rhabdomyolysis in a 61-year-old man who was not taking concomitant interacting drugs (49). 

An elderly lady with chronic renal insufficiency developed rhabdomyolysis during simvastatin therapy (50). Her symptoms of muscle pain, fatigue, myoglobuli-nuria, oliguria, and pulmonary edema occurred 48 hours after the first dose of simvastatin. Simvastatin was immediately withdrawn, and she was dialysed for 1 week. 

Ketoconazole can also cause rhabdomyolysis when taken with both lovastatin and simvastatin (77). 

A 73-year-old woman had rhabdomyolysis, cholestatic hepatitis, and mild renal insufficiency 14 days after she started to take the centrally acting muscle relaxant chlorzoxazone while also taking simvastatin (79). Withdrawal of the causal medication and conservative therapy with volume substitution and forced diuresis was followed by almost complete resolution of the symptoms. 

Most drug interactions associated with rhabdomyolysis occur when ciclosporin is combined with simvastatin or lovastatin. It has been suggested that if a statin is to be combined with ciclosporin, pravastatin or fluvastatin should be chosen instead (80). 

Pershad A, Cardello FP. Simvastatin and rhabdomyolysis—a case report and brief review. J Pharm Technol 1999 15 88-9. 

Al Shohaib S. Simvastatin-induced rhabdomyolysis in a patient with chronic renal failure. Am J Nephrol 2000 20(3) 212-3. 

Gilad R, Lampl Y. Rhabdomyolysis induced by simvastatin and ketoconazole treatment. Clin Neuropharmacol 1999 22(5) 295-7. 

Bielecki JW, Schraner C, Briner V, Kuhn M. Rhabdomyolyse und cholestatische Hepatitis unter der Behandlung mit Simvastatin und Chlorzoxazon. [Rhabdomyolysis and cholestatic hepatitis under treatment with simvastatin and chlorzoxazone.] Schweiz Med Wochenschr 1999 129(13) 514-8. 

Stirling CM, Isles CG. Rhabdomyolysis due to simvastatin in a transplant patient Are some statins safer than others Nephrol Dial Transplant 2001 16(4) 873-4. 

Yuen SL, McGarity B. Rhabdomyolysis secondary to interaction of fusidic acid and simvastatin. Med J Aust 2003 179 172. 

Simvastatin is an HMG Co-A reductase inhibitor. Its most serious adverse effect is rhabdomyolysis, which is enhanced by other drugs that inhibit CYP3A4 (1). 

A 53-year-old man taking simvastatin 40 mg/day developed rhabdomyolysis and hepatitis and had a raised serum lactate concentration (8.3 mmol/1 reference range 0.5-2.2) (8). Everything resolved 7 days after drug withdrawal. 

Rhabdomyolysis has been reported in patients taking simvastatin (28,29). Of 66 patients who took simvastatin for 1 year, two had myalgia and weakness with creatine kinase activity above 3000 (normally less than 100) (30). 

Rhabdomyolysis due to an interaction of simvastatin with diltiazem has been reported (41). 

A potential drug interaction between simvastatin and danazol, causing rhabdomyolysis and acute renal insufficiency, has been reported (43). Rhabdomyolysis can occur with all statins when they are used alone and particularly when they are combined with other drugs that are themselves myotoxic or that increase the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral systemic availability. 

Severe rhabdomyolysis occurred in a 52-year-old woman taking a combination of gemfibrozil and simvastatin (44). 

In two cases, rhabdomyolysis was caused by itraconazole in heart transplant recipients taking long-term ciclosporin and simvastatin (48,49). To avoid severe myopathy, ciclosporin concentrations should be monitored frequently and statins should be withdrawn or the dosage should be reduced, as long as azoles need to be prescribed in transplant recipients. Patients need to be educated about signs and symptoms that require immediate physician intervention. 

A 49-year-old man developed rhabdomyolysis after taking simvastatin 80 mg/day combined with clarithromycin 500 mg bd for 6 weeks (55). This effect was probably causal according to the Naranjo algorithm. 

An interaction with warfarin with resulting acute rhabdomyolysis has been observed in a patient taking simvastatin (59). This has not been observed with other statins. 

Berland Y, Vacher Coponat H, Durand C, Baz M, Laugier R, Musso JL. Rhabdomyolysis with simvastatin use. Nephron 1991 57(3) 365-6. 

Roten L, Schoenenberger RA, Krahenbuhl S, Schhenger RG. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother 2004 38(6) 978-81. 

Peces R, Pobes A. Rhabdomyolysis associated with concurrent use of simvastatin and diltiazem. Nephron 2001 89(l) 117-8. 

Andreou ER. Potential drug interaction between simvastatin and danazol causing rhabdomyolysis. Can J Clin Pharmacol 2003 10 172-4. 

Tal A, Rajeshawari M, Isley W. Rhabdomyolysis associated with simvastatin-gemfibrozil therapy. South Med J 1997 90(5) 546-7. 

Vlahakos DV, Manginas A, Chilidou D, Zamanika C, Alivizatos PA. Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine. Transplantation 2002 73(12) 1962-4. 

Maxa JL, Melton LB, Ogu CC, Sills MN, Limanni A. Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole. Ann Pharmacother 2002 36(5) 820-3. 

Lee AJ, Maddix DS. Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin. Ann Pharmacother 2001 35(1) 26-31. 

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