Weakness simvastatin

Simvastatin is a statin. Patients taking statins must be advised to immediately report any unexplained muscle pain, tenderness and weakness and to take the dose preferably at night. Patients must also be advised to follow dietary measures, namely ovoid fatty foods and maintain a high-fibre diet. 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

Simvastatin (Zocor) [Anrilipemic/HMG-CoA Reductase Inhibitor] Uses X Cholesterol Action HMG-CoA reductase inhibitor Dose Adults. 5-80 mg PO w/ meals X in renal insuff Peds. 10-17 y 10 mg, 40 mg/daily max Caution [X, —] Avoid concurrent use of gemfibrozil Contra PRG, liver Dz Disp Tabs 5,10, 20, 40, 80 mg SE HA, GI upset, myalgia, myopathy (muscle pain, tenderness or weakness w/ creatine kinase 10 x ULN), Hep Interactions T Effects OF digoxin, warfarin T risk of myopathy/iiiabdomyolysis W/ amiodarone, cyclosporine, CYP3A4 inhibitors, fibrates, HIV protease inhibitors, macrolides, niacin, verapamil, grapefruit juice X effects W/ cholestyramine, colestipol, fluvas-tatin, isradipine, propranolol EMS T Effects of warfarin use amiodarone and... 

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. 

A 56-year-old man taking simvastatin was given clarithromycin and amiodarone for pneumonia and a supraventricular tachycardia. He found it difficult to move and complained of general weakness and muscle pain. The blood creatine kinase activity was over 20 000 IU/... 

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). 

In a meta-analysis of megatrials with simvastatin, the overall incidence of myopathy was 0.025% (32). The authors suggested that potent inhibitors of CYP3A4 greatly increase the risk, but that weak inhibitors do not. Episodes of gout occurred in three of nine patients with chronic renal insufficiency who took simvastatin (33). 

A 63-year-old white man with insulin-dependent diabetes and recent coronary artery bypass surgery developed diffuse muscle pain with generalized muscular weakness after taking amiodarone 1 g/day for 10 days then 200 mg/ day plus simvastatin 40 mg/day (37). He had a significant increase in creatine kinase activity, peaking at 40 392 U/l. 

A 75-year-old-man taking simvastatin 80 mg/day and diltiazem 240 mg/day developed extreme weakness and diffuse muscle pain. All drugs were withdrawn and he underwent hemodialysis. Within 3 weeks his muscle pain disappeared and he regained function in his legs. The activities of creatine kinase and transaminases gradually returned to normal, but he continued to need hemodialysis. 

A 64-year-old African-American man developed worsening renal insufficiency, raised creatine kinase activity, diffuse muscle pain, and severe muscle weakness. He had been taking simvastatin for about 6 months and clarithromycin for sinusitis for about 3 weeks. He was treated aggressively with intravenous hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy showed necrotizing myopathy secondary to a toxin. He continued to receive intermittent hemodialysis until he died from infectious complications 3 months after admission. 

Simvastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) 10 times above the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and very rare fatalities have occurred. 

The FASTER randomized controlled pilot trial studied the benefit of clopidogrel versus placebo and simvastatin versus placebo initiated within 24-hours of symptom onset in patients with TIA or minor stroke, all of whom were treated with aspirin (Kennedy et al. 2007). The primary outcome was any stroke (ischemic and hemorrhagic) within 90 days. Minor stroke was defined as a score < 3 on the National Institutes of Health Stroke Scale (NIHSS) at the time of randomization and TIA was defined in the usual way. In addition, patients were excluded if they did not have weakness or speech disturbance or if symptom duration was less than five minutes. 

This topic has been re-analysed in a systematic review of published papers, in which relevant information from a total of 34 patients was identified (163). AU but two patients were also taking concomitant drugs known to affect the muscles, among which glucocorticoids, simvastatin, lovastatin, colchicine, and pyrazinamide were the most frequently cited. Ciclosporin is therefore difficult to implicate in most patients, but at least one case with positive ciclosporin re-administration supported a causative role. The clinical picture was non-specific, with myalgia, cramps, and muscle weakness, sometimes associated with raised serum creatine kinase activity, and heterogeneous histopathology. FinaUy, skeletal muscle abnormalities have rarely been described in patients without muscle symptoms. 

A 51-year-old woman taking zidovudine, lamivudine, indinavir, and simvastatin started to take ritonavir and after 1 week developed diffuse muscle weakness and body aches. Creatine kinase (total and the MB isozyme), lactate dehydrogenase, and transaminases were all raised. There were crystals and hemoglobin in the urine. 

Human menopausal gonadotropin-CoA reductase inhibitors Sertraline, paroxetine, fluvoxamine, and fluoxetine may inhibit the metabolism of lovastatin and simvastatin resulting in myosis and rhabdomyolysis although its inhibition is weak, these combinations are best avoided. 

An 83-year-old man who had been taking multiple medications including simvastatin 40 mg daily for 2 years was given fluconazole 400 mg daily as part of a prophylactic regimen against chemotherapy-induced neutropenic sepsis. After one week he developed generalised muscle weakness and was found to have brown urine and an elevated serum creatine kinase. His medication was stopped, and he was treated with hydration and diuretics, after which his symptoms resolved. ... 

A patient with chronic renal failure who had been taking simvastatin for 2 years was given colchieine for gout. Within 2 weeks he developed muscle weakness, whieh was diagnosed as myopathy. Both drugs were stopped and the symptoms resolved. ... 

A 68-year-old man who had been taking simvastatin 40 mg daily longterm without problem developed rhabdomyolysis (progressive muscle pain and weakness, tea-coloured urine, renal impairment, and a raised creatine phosphokinase) within 3 weeks of starting to take danazol 200 mg three times daily. He was given haemodialysis and subsequently recovered. 

These appear to be the only reports of this apparent interaction, but the pharmacokinetic basis of the interaction seems to be established. The US manufacturers of lovastatin suggest that the dose should not exceed 20 mg daily in the presence of danazol. Similarly the manufacturers of simvastatin suggest that the dose should not exceed 10 mg daily in the presence of danazol. It would seem prudent to reinforce the symptoms of myopathy and tell patients to report any unexplained muscle pain, tenderness or weakness. The authors of the lovastatin report point out that, as in this case, severe lovastatin muscle toxicity may be very slow to develop. See also muscle toxicity , (p.l086), for further guidance on monitoring, and risk factors for muscle toxicity. 

A 51-year-old woman was admitted to hospital with a 4-day history of muscular aches and weakness. Among other drugs, she had been taking zidovudine, lamivudine, indinavir, and simvastatin for 2 years. Ritonavir 100 mg twice daily had been added to her usual regimen 2 weeks previously. The rhabdomyolysis was therefore attributed to an interaction between ritonavir and simvastatin. Another similar case has also been reported. See also (b) above and (e) below for interactions of ritonavir combined with other protease inhibitors. 

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