Rosuvastatin Calcium

Trade Names:
Crestor
- Tablets 5 mg
- Tablets 10 mg
- Tablets 20 mg
- Tablets 40 mg

Pharmacology

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Inhibits HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.

Pharmacokinetics

Absorption

Absolute bioavailability is about 20%. C _max is reached in 3 to 5 h.

Distribution

The mean steady-state Vd is about 134 L. Rosuvastatin is 88% protein bound, mainly to albumin.

Metabolism

Rosuvastatin's major metabolite is formed by CYP2C9.

Not extensively metabolized; about 10% recoverable as a metabolite.

Elimination

Primarily excreted in the feces (90%). The elimination half-life is about 19 h.

Special Populations

Plasma concentrations increase about 3-fold in patients with severe renal function impairment (CrCl less than 30 mL/min). Mild to moderate renal function impairment did not affect plasma levels.

C _max and AUC are increased.

No differences in plasma concentrations between patients 65 yr of age and older compared with younger patients.

No differences in plasma concentrations between men and women.

An approximate 2-fold increase in median exposure has been demonstrated in Asian subjects. No clinically important differences in pharmacokinetics have been found among Afro-Caribbean, black, white, or Hispanic patients.

Median exposure in Asian subjects was approximately 2-fold more compared with a white control group.

Steady-state plasma concentrations in patients on chronic hemodialysis are approximately 50% higher compared with subjects with healthy renal function.

Indications and Usage

As an adjunct to diet to reduce elevated total cholesterol (total-C), LDL-C, non–HDL-C, apolipoprotein B (apo B), and triglyceride (TG) levels, and to increase HDL-C in patients with primary hypercholesterolemia and mixed dyslipidemia; as an adjunct to diet for the treatment of patients with elevated serum TG levels; as an adjunct to other lipid-lowering treatments, or alone if such treatments are not available; to reduce LDL-C, total-C, and apo B in patients with homozygous familial hypercholesterolemia; as an adjunct to diet to slow the progression of atherosclerosis in adults as part of a treatment strategy to lower total-C and LDL-C to target levels.

Contraindications

Pregnancy; breast-feeding; active liver disease or unexplained, persistent elevations of serum transaminases; hypersensitivity to any component of the product.

Dosage and Administration

PO Start with 10 mg once daily. For patients with marked hyperlipidemia (LDL-C more than 190 mg/dL) and aggressive lipid targets, consider starting with 20 mg once daily. After initiation or upon titration, analyze lipid levels within 2 to 4 wk and adjust dose accordingly.

PO Limit rosuvastatin dosage to 10 mg once daily.

PO Avoid concurrent therapy with gemfibrozil; however, if used in combination with gemfibrozil, the dosage of rosuvastatin should be limited to 10 mg once daily. The risk of skeletal muscle effects may be enhanced when rosuvastatin is used in combination with fenofibrate or niacin; therefore, consider a reduction in rosuvastatin.

PO Start with 20 mg once daily (max, 40 mg/day).

PO Start with 5 mg once daily.

PO Limit dosage of rosuvastatin to 5 mg/day.

PO In patients with severe renal function impairment (CrCl less than 30 mL/min per 1.73 m ² ) not on hemodialysis, start with 5 mg once daily (max, 10 mg once daily).

General Advice

• Administer as a single dose at any time of day, with or without food.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F). Protect from moisture.

Drug Interactions

Rosuvastatin plasma concentrations may be decreased. Administer antacid 2 h after rosuvastatin.

Plasma concentrations of rosuvastatin may be elevated, increasing the risk of adverse reactions.

Ethinyl estradiol and norgestrel plasma concentrations may be elevated.

Rosuvastatin concentrations may be elevated, increasing adverse reactions (eg, rhabdomyolysis).

Both fenofibrate and rosuvastatin concentrations may be increased.

May increase the risk of adverse reactions (eg, rhabdomyolysis).

Anticoagulant effect of warfarin may be enhanced, increasing the risk of bleeding.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (6%); asthenia (5%); dizziness (4%); memory loss (postmarketing).

GI

Nausea (6%); constipation (5%); abdominal pain (at least 2%); pancreatitis.

Hepatic

Hepatitis, jaundice (postmarketing).

Hypersensitivity

Hypersensitivity including rash, pruritus, urticaria, and angioedema.

Lab Tests

Elevated CPK (3%); elevated ALT (2%); dipstick-positive proteinuria and microscopic hematuria; elevated alkaline phosphatase, bilirubin, glucose, glutamyl transpeptidase, and transaminase; thyroid function abnormalities.

Musculoskeletal

Myalgia (13%); arthralgia (10%).

Precautions

Pregnancy

Category X .

Lactation

Contraindicated.

Children

Safety and efficacy not established.

Renal Function

Adjust the dose in patients with severe renal function impairment (CrCl less than 30 mL/min) not requiring hemodialysis.

Hepatic Function

Contraindicated in patients with active liver disease, which may include patients with unexplained, persistent elevations in transaminase levels.

Endocrine effects

Use caution when administering with drugs that affect steroid levels or activity (eg, ketoconazole, spironolactone).

Liver enzyme abnormalities

Increases in transaminases have been reported. Use with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease.

Proteinuria and hematuria

Consider a dose reduction in patients with unexplained, persistent proteinuria and/or hematuria during routine urinalysis.

Skeletal muscle effects

Rhabdomyolysis with renal dysfunction secondary to myoglobinuria has been reported with rosuvastatin. Temporarily withhold therapy in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis (eg, hypotension, sepsis). The risk of myopathy with other drugs in this class is increased if cyclosporine, gemfibrozil, lopinavir/ritonavir, or niacin is coadministered. Consider myopathy in any patient with diffuse myalgia, muscle tenderness or weakness, or marked elevation of CPK.

Overdosage

Symptoms

The symptoms of overdose are unknown.

Patient Information

• Advise patient to take once daily as prescribed, without regard to meals, but to take with food if stomach upset occurs.
• Advise patient to try to take each dose at about the same time each day.
• Inform patient that drug helps control, but does not cure, cholesterol abnormality, and to continue taking drug as prescribed if cholesterol levels are lowered.
• Advise patient that if a dose is missed, to take it as soon as remembered, but to never take more than 1 dose of rosuvastatin a day.
• Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
• Emphasize to patient importance of the following other modalities of cholesterol control: dietary changes (reduce saturated fat intake, increase soluble fiber intake), weight control, regular exercise, and smoking cessation.
• Advise women of childbearing potential to use effective contraception during treatment with rosuvastatin.
• Advise patient who is also using an aluminum and magnesium hydroxide combination antacid to take the antacid at least 2 h after taking rosuvastatin.
• Instruct patient to notify health care provider if experiencing any unexplained muscle pain, tenderness, and/or weakness, or any other unusual feelings.

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