Rosuvastatin

Generic Name

Rosuvastatin calcium

Brand Names

Crestor

Ezallor Sprinkle

Rosulip

Roswin

Rovas

Many region-specific brands are available internationally

Drug Class

HMG-CoA reductase inhibitor

Lipid-lowering agent

Statin class

Mechanism of Action

Rosuvastatin inhibits 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the mevalonate pathway responsible for cholesterol biosynthesis in the liver

Inhibition of HMG-CoA reductase leads to decreased hepatic cholesterol synthesis and upregulation of LDL receptors on hepatocyte membranes

This results in increased clearance of low-density lipoprotein cholesterol (LDL-C) from the blood

Rosuvastatin also reduces total cholesterol (TC), triglycerides (TG), apolipoprotein B (apoB), and mildly increases high-density lipoprotein cholesterol (HDL-C)

Rosuvastatin has a higher affinity for HMG-CoA reductase compared to other statins and demonstrates greater LDL-lowering potency

Indications

Approved Indications

Primary hyperlipidemia and mixed dyslipidemia

Hypertriglyceridemia

Homozygous familial hypercholesterolemia

Primary dysbetalipoproteinemia

Prevention of cardiovascular events in patients at high risk (including diabetics and patients with established coronary artery disease)

Pediatric familial hypercholesterolemia (heterozygous)

Off-Label Uses

Non-alcoholic fatty liver disease (NAFLD)

Chronic kidney disease-related dyslipidemia

Polycystic ovary syndrome (PCOS)-related lipid abnormalities

Anti-inflammatory or pleiotropic effects in atherosclerosis

Dosage and Administration

Initial Adult Dose

5 mg to 10 mg orally once daily

Initiated based on baseline LDL-C, cardiovascular risk, and tolerability

Asian patients and those predisposed to myopathy start at 5 mg

Titration and Maximum Dose

Adjust dose at 4-week intervals

Maximum dose: 40 mg once daily

40 mg dose reserved for patients with severe hyperlipidemia and high cardiovascular risk who have not responded to lower doses

Pediatric Dose

For children with familial hypercholesterolemia

Ages 8–17: typically 5 mg to 20 mg once daily (adjusted by weight and response)

Safety established in children ≥8 years

Route and Timing

Administer orally once daily, with or without food

Best taken at the same time daily

Can be administered at any time of day due to long half-life

Pharmacokinetics

Absorption

Bioavailability: ~20%

Peak plasma concentration occurs about 3 to 5 hours post-dose

Distribution

Volume of distribution: ~134 L

94% bound to plasma proteins (primarily albumin)

Metabolism

Minimal hepatic metabolism (approximately 10%)

Metabolized mainly by CYP2C9 and minimally by CYP2C19

Less dependent on CYP3A4 compared to atorvastatin or simvastatin

Excretion

Primarily excreted in feces (~90%) as unchanged drug

Urine excretion ~10%

Half-life ~19 hours

Does not undergo significant enterohepatic recirculation

Contraindications

Active liver disease or unexplained persistent elevations of hepatic transaminases

Pregnancy

Lactation

Known hypersensitivity to rosuvastatin or any component of the formulation

Concomitant use with cyclosporine or certain combinations (in specific doses)

Warnings and Precautions

Myopathy and Rhabdomyolysis

Dose-dependent risk

Risk increased with concomitant use of fibrates, niacin, cyclosporine, or protease inhibitors

Patients should report unexplained muscle pain, tenderness, or weakness

Creatine kinase (CK) should be monitored if symptoms develop

Liver Enzyme Elevation

Monitor liver transaminases before starting therapy and periodically thereafter

Discontinue if ALT or AST increases persistently >3× upper limit of normal

Proteinuria and Hematuria

Transient, dose-related proteinuria and hematuria have been observed

Usually benign and resolves without sequelae

Diabetes Risk

Slight increased risk of elevated HbA1c or fasting glucose

Evaluate glycemic control in prediabetic or diabetic patients

Cognitive Effects

Rare reports of memory loss, forgetfulness, or confusion

Typically reversible upon discontinuation

Use in Asian Populations

Higher plasma concentrations due to pharmacokinetic variability

Lower starting dose recommended (5 mg)

Hypothyroidism and Renal Impairment

Both can predispose to myopathy

Correct thyroid dysfunction and adjust dosing in renal disease

Adverse Effects

Very Common

Headache

Myalgia

Abdominal pain

Nausea

Asthenia

Common

Dizziness

Constipation

Increased liver enzymes (ALT, AST)

CK elevation

Proteinuria

Arthralgia

Less Common

Pancreatitis

Thrombocytopenia

Depression

Sleep disturbances

Peripheral neuropathy

Rare but Serious

Rhabdomyolysis

Hepatotoxicity

Interstitial lung disease

Immune-mediated necrotizing myopathy

Anaphylaxis

Overdose

Symptoms

No specific overdose pattern

May include liver enzyme elevations or myopathy

Management

Symptomatic and supportive care

Hemodialysis is not useful due to high protein binding

Drug Interactions

Cyclosporine

Increases rosuvastatin plasma levels significantly

Contraindicated with 10 mg or higher

Use lower doses (maximum 5 mg) if unavoidable

Gemfibrozil and Fibrates

Increased risk of myopathy and rhabdomyolysis

Avoid concurrent use or use with caution

Fenofibrate is preferred if fibrate needed

Warfarin

Increases INR

Monitor closely when initiating or adjusting rosuvastatin

Protease Inhibitors (ritonavir, lopinavir)

Can raise rosuvastatin exposure

Limit rosuvastatin dose to 10 mg daily

Antacids (aluminum and magnesium hydroxide)

Reduce rosuvastatin absorption

Separate administration by 2 hours

Niacin

Increased risk of skeletal muscle effects

Caution if combined for lipid modification

Concomitant Statins or CYP Inhibitors

Combination increases risk of toxicity

Avoid unless clinically indicated and under close monitoring

Use in Special Populations

Pregnancy

Contraindicated

Cholesterol synthesis essential for fetal development

Category X (prior FDA classification)

Lactation

Excreted in breast milk

Contraindicated

Pediatrics

Approved for use in children aged ≥8 years for familial hypercholesterolemia

Titration required based on growth, LDL targets, and tolerance

Geriatrics

Increased systemic exposure possible

Higher risk of myopathy and renal impairment

No dose adjustment required but start at lower dose

Hepatic Impairment

Contraindicated in active liver disease

Use caution in mild hepatic impairment

Renal Impairment

Dose adjustment required in severe renal dysfunction (eGFR <30 mL/min/1.73m²)

Avoid 40 mg dose in patients with moderate renal impairment

Monitoring Parameters

Lipid profile: baseline and 4–12 weeks after initiation or dose adjustment

Liver function tests: baseline and as clinically indicated

Creatine kinase: baseline if patient is at high risk of myopathy or symptomatic

HbA1c or fasting glucose in patients with risk factors for diabetes

Urine analysis in patients on higher doses for proteinuria

INR if on warfarin

Comparative Pharmacology

Rosuvastatin vs Atorvastatin

Rosuvastatin has greater potency for LDL-C lowering

Rosuvastatin less CYP3A4 metabolism = fewer drug interactions

Atorvastatin better evidence in secondary prevention post-MI

Rosuvastatin vs Simvastatin

Rosuvastatin provides superior LDL-C reduction at lower doses

Simvastatin has more CYP3A4 metabolism and greater myopathy risk at high doses

Rosuvastatin vs Pravastatin

Pravastatin is less potent but safer in polypharmacy due to non-CYP metabolism

Rosuvastatin better for high-intensity lipid lowering

Rosuvastatin vs Ezetimibe

Ezetimibe inhibits intestinal cholesterol absorption

Often used in combination with statins for synergistic LDL-C reduction

Formulations Available

Tablets: 5 mg, 10 mg, 20 mg, 40 mg

Sprinkle capsule: Ezallor (delayed-release for patients with swallowing difficulties)

Fixed-dose combinations:

Rosuvastatin + Ezetimibe

Rosuvastatin + Aspirin (for cardiovascular prevention)

Regulatory and Legal Status

Prescription-only medication

Approved globally for primary and secondary prevention of cardiovascular disease

Listed in WHO Model List of Essential Medicines for management of lipid disorders