Pharmacology Update

Rosuvastatin Calcium (Crestor)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved another HMG-CoA reductase inhibitor (statin) for the treatment of elevated cholesterol. Rosuvastatin is a potent new statin that is not extensively metabolized and has low potential for drug interaction. It is licensed from Shionogi in Japan and marketed by AstraZeneca as Crestor.

Indications

Rosuvastatin is indicated as an adjunct to diet to reduce elevated total cholesterol, LDL-cholesterol, ApoB, nonHDL-cholesterol and triglycerides, and to increase HDL-cholesterol in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Type IIa and IIb). It is also indicated for patients with elevated triglycerides (Fredrickson Type IV) and patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments to lower LDL-cholesterol, total-cholesterol, and ApoB.1

Dosage

The dose range for rosuvastatin is 5-40 mg depending on goal of therapy, concomitant drugs, and patient response. The usual starting dose is 10 mg daily and 20 mg daily for patients with homozygous familial hypercholesterolemia. It may be taken at any time of day and without regard to meals, and no dosage adjustment is needed for patients with mild-to-moderate renal impairment. In patients with severe renal impairment not on hemodialysis, the starting dose is 5 mg daily, and in those taking cyclosporine, the dose should be limited to 5 mg daily.1 Rosuvastatin is available as 5-mg, 10-mg, 20-mg, and 40-mg tablets.

Potential Advantages

Rosuvastatin is not extensively metabolized by the cytochrome P450 enzyme system, and, as a result, drug interactions associated with other statins are not associated with rosuvastatin.1 Rosuvastatin appears to be the most potent statin on a milligram basis. In a 12-week, randomized, double-blind, placebo-controlled, comparative study, rosuvastatin 5 mg and 10 mg produced a greater reduction in LDL-C than atorvastatin 10 mg.2 LDL-C reductions were 40% and 43% for rosuvastatin 5 mg (n =128) and 10 mg (n = 129), respectively, compared to 35% for atorvastatin 10 mg (n = 127). These were significant at P < 0.01 and P < 0.001, respectively. At those doses, 42% and 47% of patients on rosuvastatin met NCEP ATP III goal compared to 19% for atorvastatin.

Potential Disadvantages

Higher doses of rosuvastatin (ie, 40 mg and 80 mg) appeared to be associated with a higher frequency of proteinuria of 2+ or higher compared to the same dose of atorvastatin.5 The frequencies were 2.8% and 11%, respectively, compared to 0.4% and 0.3% for atorvastatin 40 mg and 80 mg. There is limited clinical experience with rosuvastatin. While it appears to be well tolerated, its safety profile needs to be confirmed with further clinical studies and postmarketing surveillance.

Comments

Rosuvastatin is a potent, hydrophilic HMG-CoA reductase inhibitor (statin) with a low potential for drug interactions and a long elimination half-life (about 19 hours). In patients with hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Type IIa and IIb), rosuvastatin 10 mg reduced LDL-C by about 50%, total cholesterol by about 36%, and triglycerides by about 10% at 6 weeks.1-3 In comparative studies, rosuvastatin is more potent than atorvastatin and simvastatin on a mg-for-mg basis.1,2,4 The drug appears to be well tolerated and the overall incidence of adverse events were similar to other statins with the possible difference of proteinuria.4

The average wholesale cost of rosuvastatin is $2.63 per tablets for all strengths. This is 12% less than the average weighted cost for atorvastatin.6

Clinical Implications

Statins are the firstline pharmacological management of hypercholesterolemia. Rosuvastatin offers a potent new agent in this class with a low risk for drug interactions. Due to rosuvastatin’s potency, a higher percent of patient may achieve NCEP LDL-C goals compared to currently available statins.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.

References

1. Crestor Product Information. AstraZeneca. August 2003.

2. Davidson M, et al. Am J Cardiol. 2002;89(3):268-275.

3. Olsson AG, et al. Am J Cardiol. 2002;88(5):504-508.

4. Carswell CI, et al. Drugs. 2002;62(14):2075-2085.

5. FDC Report. The Pink Sheet. 2003;65(33):4-5.

6. FDC Report. The Pink Sheet. 2003;65(33):3.