Rosuvastatin is a highly potent, synthetic HMG-CoA reductase inhibitor (statin) widely prescribed for the management of dyslipidemia. As a third-generation statin, it demonstrates superior efficacy in lowering low-density lipoprotein cholesterol (LDL-C) and raising high-density lipoprotein cholesterol (HDL-C) compared to many other agents in its class. Its robust evidence base supports its use in both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), making it a cornerstone therapy in modern cardiology and preventive medicine. This profile provides a comprehensive, expert-level overview of its pharmacological characteristics, clinical applications, and essential safety information.

Features

• Active Ingredient: Rosuvastatin calcium.
• Pharmacological Class: Selective and competitive HMG-CoA reductase inhibitor.
• Standard Available Strengths: 5 mg, 10 mg, 20 mg, 40 mg tablets.
• High Potency: Exhibits some of the highest LDL-C reduction per milligram among available statins.
• Extended Half-Life: Approximately 19 hours, allowing for consistent 24-hour enzyme inhibition and flexible once-daily dosing.
• Minimal CYP450 Metabolism: Primarily metabolized via CYP2C9 to a limited extent (approximately 10%), with minimal interaction with the CYP3A4 pathway, reducing its potential for certain drug-drug interactions.
• Dual Excretion: Approximately 90% excreted unchanged in feces (via biliary excretion), with 10% excreted in urine.

Benefits

• Significant LDL-C Reduction: Achieves marked reductions in atherogenic LDL cholesterol, the primary target for ASCVD risk mitigation, with reductions of 45-63% observed at standard doses.
• Atherosclerotic Plaque Stabilization and Regression: Contributes to the stabilization of vulnerable coronary plaques by reducing their lipid core and inflammatory activity, thereby decreasing the risk of rupture and subsequent acute coronary syndromes.
• Favorable Effect on HDL-C: Consistently demonstrates a modest increase in cardioprotective HDL cholesterol levels.
• Reduction in Triglyceride Levels: Effective in lowering elevated triglyceride levels, another independent risk factor for pancreatitis and cardiovascular disease.
• Proven Reduction in Major Adverse Cardiac Events (MACE): Robust clinical trial data, including the JUPITER trial, demonstrates significant reductions in the risk of myocardial infarction, stroke, and cardiovascular mortality in appropriate patient populations.
• Comprehensive Lipid Management: Offers a holistic approach by improving the entire lipid profile (LDL-C, HDL-C, Triglycerides) and associated atherogenic particle counts.

Common use

Rosuvastatin is indicated as an adjunct to diet for the reduction of elevated total-C, LDL-C, ApoB, non-HDL-C, and triglycerides, and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. It is also indicated to slow the progression of atherosclerosis and for the primary prevention of cardiovascular events in individuals without clinically evident coronary heart disease but with an increased risk based on age, elevated hs-CRP, and at least one additional cardiovascular risk factor. Its use is central in both primary prevention (preventing first events) and secondary prevention (preventing recurrent events) strategies as per current ACC/AHA and ESC/EAS guidelines.

Dosage and direction

The dosage of rosuvastatin must be individualized based on the patient’s lipid goals, underlying risk factors, and therapeutic response. Therapy should be initiated with a appropriate starting dose, which may be adjusted at 4-week intervals based on LDL-C response and tolerability.

• Starting Dose: The recommended usual starting dose is 10 mg or 20 mg orally once daily. For patients requiring more than a 45% LDL-C reduction, a 20 mg starting dose may be considered.
• Dose Range: 5 mg to 40 mg once daily. The 40 mg dose is reserved for patients who do not achieve their LDL-C goal with 20 mg and should only be used in patients with severe hypercholesterolemia and high cardiovascular risk.
• Administration: Can be taken with or without food, at any time of day. Consistency in timing is recommended.
• Special Populations:
  • Asian Patients: Pharmacokinetic studies show an approximate 2-fold increase in median exposure in Asian subjects. Consideration should be given to initiating therapy at 5 mg.
  • Renal Impairment: For patients with severe renal impairment (CrCl <30 mL/min/1.73m²) not on hemodialysis, the recommended starting dose is 5 mg, not to exceed 10 mg.
  • Patients on Cyclosporine: Contraindicated.
  • Patients Pre-disposed to Myopathy: A 5 mg starting dose is recommended.

Precautions

• Skeletal Muscle Effects: Patients should be advised to report promptly any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, as these may be signs of rare but serious myopathy, including rhabdomyolysis.
• Liver Enzyme Monitoring: Liver function tests (LFTs) should be performed before initiating therapy and as clinically indicated thereafter. An increase in serum transaminases can occur, which is usually transient and asymptomatic.
• HbA1c/Fasting Glucose: Statin therapy, including rosuvastatin, is associated with a slight increased risk of raising HbA1c and fasting serum glucose levels. The cardiovascular benefits generally outweigh this risk, but it should be monitored.
• Renal Function: As rosuvastatin is excreted renally to a small degree, caution is advised in patients with severe renal impairment, requiring dose limitation.
• Alcohol: Patients should be cautioned about excessive alcohol consumption, as this may increase the risk of hepatotoxicity.

Contraindications

• Hypersensitivity to rosuvastatin or any component of the formulation.
• Active liver disease or unexplained persistent elevations of serum transaminases.
• Pregnancy and lactation (Category X). Cholesterol and products synthesized from cholesterol are essential for fetal development. Statins are contraindicated in women who are or may become pregnant.
• Concomitant use with cyclosporine.

Possible side effect

The majority of patients tolerate rosuvastatin well. Side effects are generally mild and transient.

• Common (>1/100, <1/10): Headache, dizziness, nausea, constipation, abdominal pain, myalgia (muscle ache), asthenia (weakness).
• Uncommon (>1/1000, <1/100): Pruritus (itching), rash, urticaria (hives).
• Rare (<1/1000):
  • Myopathy/Rhabdomyolysis: Characterized by muscle pain, tenderness, or weakness with CK elevations >10 times ULN. Myositis and autoimmune myopathy have also been reported.
  • Hepatobiliary disorders: Hepatitis, jaundice.
  • Immune System: Hypersensitivity reactions, including angioedema.
  • Nervous System: Memory loss, confusion.
  • Reproductive System: Gynecomastia (very rare).

Drug interaction

• Cyclosporine: Contraindicated. Concomitant use increases rosuvastatin exposure significantly (up to 7-fold) and dramatically increases the risk of myopathy/rhabdomyolysis.
• Gemfibrozil and other Fibrates: Avoid concomitant use with gemfibrozil. If used with other fibrates (e.g., fenofibrate), the benefit of combined therapy should be carefully weighed against the increased risk of myopathy. Use the lowest necessary dose of rosuvastatin.
• Antacids: Simultaneous administration of aluminum and magnesium hydroxide-containing antacids can decrease rosuvastatin absorption. Dosing should be separated by at least 2 hours.
• Warfarin: Rosuvastatin may potentiate the anticoagulant effect of warfarin, leading to an increase in INR. Close monitoring of INR is required during initiation and upon dosage adjustment of rosuvastatin.
• Protease Inhibitors (e.g., Lopinavir/Ritonavir): Combination may increase rosuvastatin exposure and the risk of myopathy. Use with caution and at the lowest possible dose.
• Other Lipid-Lowering Agents (Niacin): The risk of myopathy may be increased when used with niacin.

Missed dose

If a dose is missed, it should be taken as soon as remembered, unless it is almost time for the next scheduled dose. Do not double the dose to make up for a missed one. Resume the regular dosing schedule.

Overdose

There is no specific antidote for rosuvastatin overdose. In the event of an overdose, symptomatic and supportive measures should be instituted. The patient should receive appropriate supportive treatment and liver function and CK levels should be monitored. Given its extensive protein binding, rosuvastatin is not expected to be eliminated efficiently by hemodialysis.

Storage

Store at room temperature between 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C to 30°C (59°F to 86°F). Keep the container tightly closed and protect from moisture and light. Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational and informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided is based on the drug’s prescribing information but may not be all-inclusive.

Reviews

• Clinical Consensus: Rosuvastatin is regarded by the cardiology community as a highly effective and well-tolerated statin for aggressive lipid-lowering. Its potency allows for goal attainment in a high percentage of patients, even those with very high baseline LDL-C or statin intolerance to other agents.
• JUPITER Trial Landmark: The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) was a pivotal study demonstrating a 44% reduction in the primary composite endpoint (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes) in patients with normal LDL-C but elevated high-sensitivity C-reactive protein.
• Real-World Evidence: Large observational studies and registries consistently confirm its efficacy and safety profile in diverse patient populations, supporting its position as a first-line agent for ASCVD risk reduction.