Crestor Pre-Surgery Hold Window: What You Need to Know About Rosuvastatin Before an Operation

Does rosuvastatin need to be stopped before surgery?

The Crestor prescribing information treats an operation as an acute condition rather than a scheduled stop with a countdown. The label says to temporarily discontinue Crestor in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis, and it lists sepsis, shock and major surgery as examples [1]. The label notes that acute kidney injury from myoglobinuria and rare fatalities have occurred with statins [1].

The muscle risk the label describes

Listed risk factors for myopathy and rhabdomyolysis are age 65 or older, uncontrolled hypothyroidism, renal impairment, certain other drugs and a higher dose; Asian patients may be at higher risk, and 40 mg daily carries more risk than lower doses [1]. Rare immune-mediated necrotizing myopathy is also described [1]. The label directs that Crestor be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected, and it tells patients to report unexplained muscle pain, tenderness or weakness, particularly with malaise or fever [1].

Kidney function and dose ceilings

Rosuvastatin needs no dose adjustment for mild or moderate renal impairment. Severe impairment (creatinine clearance under 30 mL/min/1.73 m2, not on hemodialysis) calls for a 5 mg start and no more than 10 mg daily; exposure is about 3-fold higher in that group [1]. Plasma levels were 50% higher on chronic hemodialysis than in healthy volunteers [1]. Other ceilings in the label are 5 mg daily with cyclosporine and 10 mg daily with gemfibrozil when that combination cannot be avoided [1].

How long rosuvastatin stays in the body

The plasma half-life is about 19 hours, peak concentration arrives 3 to 5 hours after a dose and absolute bioavailability is about 20% [1]. About 90% is excreted in feces, and roughly 10% of a dose is recovered as metabolite [1]. Rosuvastatin is not a prodrug; more than 90% of circulating HMG-CoA reductase inhibitory activity is accounted for by the parent compound [1].

Drug interactions that matter around an operation

Cyclosporine raised rosuvastatin AUC about 7-fold and Cmax about 11-fold, and the label caps Crestor at 5 mg daily with it [1]. In a 10-patient heart transplant study the AUC ratio was 7.1 and the Cmax ratio 10.6 versus 21 historical healthy controls, with no change in cyclosporine levels [2]. Gemfibrozil is to be avoided; in a 20-volunteer crossover study it raised rosuvastatin AUC 1.88-fold and Cmax 2.21-fold [1][3]. Several antivirals also raise levels: atazanavir/ritonavir 3.1-fold, and sofosbuvir/velpatasvir/voxilaprevir 7.4-fold, which the label says to avoid [1]. CYP3A4 is not the main issue here; itraconazole raised AUC only about 1.4-fold [1]. The label also says rosuvastatin significantly increased INR in patients on warfarin and asks that INR be checked before starting and often enough after starting, titration or stopping [1].

What the outcome trial did not test

JUPITER randomized 17,802 apparently healthy adults to rosuvastatin 20 mg or placebo and was stopped at a median 1.9 years; LDL cholesterol fell 50%, hsCRP fell 37%, and the primary endpoint rate was 0.77 versus 1.36 per 100 person-years (hazard ratio 0.56) [4]. It was a rosuvastatin-versus-placebo trial, not a test of stopping or continuing the drug around surgery.