Rosuvastatin is a highly potent, synthetic HMG-CoA reductase inhibitor, widely recognized in clinical practice for its superior efficacy in managing dyslipidemia. As a third-generation statin, it demonstrates exceptional LDL-cholesterol reduction capabilities, significantly impacting cardiovascular risk stratification. Its hydrophilic properties contribute to a favorable pharmacokinetic profile, with selective action on hepatocytes and minimal penetration into extrahepatic tissues, reducing the potential for off-target effects. This agent is a cornerstone in both primary and secondary prevention strategies, aligning with current ACC/AHA guidelines for atherosclerotic cardiovascular disease (ASCVD) risk mitigation.

Features

• Active Ingredient: Rosuvastatin calcium
• Pharmacologic Class: HMG-CoA reductase inhibitor (statin)
• Available Strengths: 5 mg, 10 mg, 20 mg, 40 mg tablets
• Bioavailability: Approximately 20%
• Half-life: ~19 hours
• Time to Peak Plasma Concentration: 3–5 hours post-administration
• Metabolism: Minimal hepatic metabolism via CYP2C9 and CYP2C19; primarily excreted unchanged in feces
• Special Formulations: None; standard film-coated tablets

Benefits

• Achieves up to 60% reduction in LDL-C levels at maximum doses, outperforming most other statins in head-to-head trials
• Significantly lowers non-HDL cholesterol and apolipoprotein B, addressing atherogenic particle burden comprehensively
• Raises HDL cholesterol modestly but consistently, contributing to improved lipid ratios
• Demonstrates robust anti-inflammatory effects as measured by hs-CRP reduction, independent of lipid-lowering
• Reduces major adverse cardiovascular events (MACE) by 40–50% in high-risk populations over 5 years
• Slows progression and may induce regression of coronary atherosclerosis as quantified by intravascular ultrasound

Common use

Rosuvastatin is indicated as an adjunct to diet for the treatment of various dyslipidemias, including primary hypercholesterolemia and mixed dyslipidemia. It is particularly valuable in patients requiring aggressive LDL-C reduction, such as those with familial hypercholesterolemia or established ASCVD. Additionally, it is used for primary prevention in adults with elevated CRP levels without clinically evident cardiovascular disease but with increased risk based on age, hs-CRP ≥2 mg/L, and at least one additional cardiovascular risk factor. Off-label uses include polycystic ovary syndrome-associated dyslipidemia and lipid management in HIV patients on antiretroviral therapy.

Dosage and direction

Initiate treatment with 5–10 mg once daily, with or without food. Dosage should be individualized based on baseline LDL-C levels, goal of therapy, and patient response. For patients requiring more aggressive LDL-C reduction (>45%), start with 20 mg once daily. The maximum recommended dose is 40 mg reserved for patients who do not achieve goal LDL-C with 20 mg and are not of Asian ancestry or have predisposing factors for myopathy.

Dosage adjustments are necessary in specific populations:

• Asian patients: Initiate with 5 mg due to increased systemic exposure
• Renal impairment (CrCl <30 mL/min): Initial dose should not exceed 5 mg once daily
• Patients on cyclosporine: Limit to 5 mg once daily
• Concomitant gemfibrozil therapy: Avoid combination or use 5 mg once daily with extreme caution

Take consistently at the same time each day, preferably in the evening, though chronopharmacological studies show minimal difference in efficacy with timing due to long half-life.

Precautions

Monitor liver enzymes before initiation, at 12 weeks following initiation or dose escalation, and periodically thereafter. Discontinue if ALT or AST persist at >3× ULN. Assess creatine kinase (CK) levels in patients reporting unexplained muscle pain, tenderness, or weakness. Use caution in patients with history of liver disease or heavy alcohol consumption. Consider vitamin D supplementation in patients on long-term therapy due to potential reduction in vitamin D levels. Rosuvastatin may increase HbA1c and fasting serum glucose levels; monitor diabetic parameters regularly. Not recommended during pregnancy (Category X) or in nursing mothers.

Contraindications

Hypersensitivity to rosuvastatin or any component of the formulation. Active liver disease or unexplained persistent elevations of serum transaminases. Pregnancy, lactation, and women of childbearing potential not using adequate contraception. Concomitant use with cyclosporine. Patients with predisposing factors for rhabdomyolysis, including severe renal impairment (CrCl <30 mL/min), hypothyroidism, or personal/family history of hereditary muscular disorders.

Possible side effect

Common (≥5%): Headache (6.4%), myalgia (5.1%), nausea (4.8%), constipation (3.3%), abdominal pain (2.6%), asthenia (2.5%)

Less common (1–5%): Dizziness (2.4%), insomnia (1.8%), rash (1.5%), proteinuria (1.2%—typically transient and not indicative of renal injury)

Rare (<1%):

• Musculoskeletal: Rhabdomyolysis, immune-mediated necrotizing myopathy
• Hepatic: Hepatitis, jaundice
• Neurological: Memory impairment, peripheral neuropathy
• Dermatological: Photosensitivity, Stevens-Johnson syndrome
• Gastrointestinal: Pancreatitis
• Ophthalmological: Cataract progression (debated)

Laboratory abnormalities: Elevated transaminases (≥3× ULN in 0.1–0.4% of patients), increased CK (>10× ULN in 0.2–0.4%), elevated glucose (5–10 mg/dL average increase)

Drug interaction

Contraindicated combinations: Cyclosporine (increases rosuvastatin AUC 7.1-fold)

Significant interactions requiring dose limitation:

• Gemfibrozil: Increases rosuvastatin AUC 1.9-fold (max 5 mg daily)
• Lopinavir/ritonavir: Increases rosuvastatin AUC 2.1-fold (max 10 mg daily)
• Atazanavir/ritonavir: Increases rosuvastatin AUC 3.1-fold (max 10 mg daily)

Moderate interactions requiring monitoring:

• Warfarin: Rosuvastatin may potentiate anticoagulant effect (monitor INR)
• Oral contraceptives: Increases ethinyl estradiol and norgestrel AUC by 26% and 34% respectively
• Niacin (>1 g/day): May increase risk of myopathy
• Colchicine: Increased risk of myopathy, especially in elderly and renal impairment

Minimal interaction: Unlike other statins, rosuvastatin has minimal interaction with CYP3A4 inhibitors (erythromycin, ketoconazole, verapamil)

Missed dose

Take the missed dose as soon as remembered, unless it is nearly time for the next scheduled dose. Do not double the dose to make up for a missed one. The long half-life of rosuvastatin (19 hours) provides sustained lipid-lowering effect, making occasional missed doses less impactful on overall efficacy compared to shorter-acting statins. However, consistent daily adherence is crucial for optimal cardiovascular outcomes.

Overdose

No specific antidote exists. Cases of overdose have been reported with doses up to 640 mg without serious adverse effects. Suspected overdose should involve supportive measures including gastric lavage if presented within 1 hour of ingestion. Monitor for signs and symptoms of myopathy (muscle pain, weakness, dark urine) and hepatic injury. Hemodialysis is unlikely to be effective due to high protein binding (88%). Provide symptomatic treatment and monitor CK, liver enzymes, and renal function for at least 48 hours.

Storage

Store at controlled room temperature 20–25°C (68–77°F) with excursions permitted between 15–30°C (59–86°F). Protect from light and moisture. Keep in original container with tight closure. Do not store in bathroom or near kitchen sink. Keep out of reach of children and pets. Discard unused medication after expiration date printed on packaging. Do not flush medications down toilet or pour into drain unless instructed to do so.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Individual patient response to rosuvastatin may vary based on genetic factors, comorbidities, and concomitant medications. Healthcare providers should always consider the complete clinical picture when prescribing therapy. Patients should not initiate, discontinue, or modify dosage without consulting their healthcare provider. The full prescribing information should be consulted before administration.

Reviews

Clinical evidence: The JUPITER trial (n=17,802) demonstrated 44% reduction in primary endpoint (nonfatal MI, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death) in patients with LDL-C <130 mg/dL but elevated hs-CRP. Rosuvastatin 20 mg daily showed significant benefit over placebo (p<0.00001).

Meta-analyses: A 2022 Cochrane review of 18 randomized trials (n=102,154) confirmed rosuvastatin reduces all-cause mortality (RR 0.84), cardiovascular mortality (RR 0.74), and major cardiovascular events (RR 0.70) compared to placebo in primary prevention.

Real-world data: Large observational studies (n>150,000) show persistence rates of 65–75% at 12 months, superior to atorvastatin and simvastatin, with comparable safety profile.

Expert consensus: Current ACC/AHA guidelines classify rosuvastatin as a high-intensity statin (≥50% LDL-C reduction) at doses ≥20 mg daily, recommending it as first-line for very high-risk ASCVD patients.