Renal insufficiency simvastatin

Renal function impairment- Exercise caution when simvastatin is administered to patients with severe renal insufficiency. Initiate therapy in such patients with 5 mg/day and monitor closely. 

Renal function impairment Closely monitor patients with renal impairment. Higher systemic exposure of simvastatin may occur in severe renal insufficiency. Plasma concentrations after a single dose of iovastatin were approximately 2-fold higher in patients with severe renal insufficiency. Plasma concentrations of rosuvastatin increased to a clinically significant extent (about 3-fold) in patients with severe renal impairment. 

Renal function impairment For patients with severe renal insufficiency, do not start ezetimibe/simvastatin unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Exercise caution when ezetimibe/simvastatin is administered to these patients, and monitor them closely. Concomitant bile acid sequestrants Give ezetimibe/simvastatin either 2 hours or more before or 4 hours or more after administration of a bile acid sequestrant. Concomitant cyclosporine Exercise caution when initiating ezetimibe/simvastatin in the setting of cyclosporine. In patients taking cyclosporine, do not start ezetimibe/simvastatin unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Do not exceed 10 mg ezetimibe/10 mg simvastatin daily. 

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 Simvastatin was immediately withdrawn, and she was dialysed for 1 week. 

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. 

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 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. 

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. 

In another case, a 39-year-old woman mistakenly took simvastatin for weight reduction and developed a bilateral leg compartment syndrome and acute renal insufficiency due to myonecrosis [60 ]. 

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