Rosuvastatin
Brand names: Crestor, Ezallor Sprinkle
Quick Facts
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Primary hyperlipidemia & mixed dyslipidemia | Adults | Adjunct to diet | FDA Approved |
| Hypertriglyceridemia | Adults | Adjunct to diet | FDA Approved |
| Primary dysbetalipoproteinemia (Type III) | Adults | Adjunct to diet | FDA Approved |
| Homozygous familial hypercholesterolemia (HoFH) | Adults and pediatric patients ≥7 years | Alone or with other LDL-lowering therapy (e.g., LDL apheresis, ezetimibe, PCSK9 inhibitors) | FDA Approved |
| Heterozygous familial hypercholesterolemia (HeFH) | Adults and pediatric patients ≥8 years | Adjunct to diet | FDA Approved |
| Slowing progression of atherosclerosis | Adults | Adjunct to diet | FDA Approved |
| Reduction of major cardiovascular events (MI, stroke, arterial revascularization, CV death) | Adults without clinically evident CHD; men ≥50 and women ≥60 with hsCRP ≥2 mg/L plus ≥1 additional CV risk factor | Adjunct to diet | FDA Approved |
Rosuvastatin is among the most potent statins on a milligram basis, producing approximately 45–55% LDL-C reduction across the approved 5–40 mg dose range (VOYAGER pooled estimates). It is widely used for ASCVD secondary prevention, primary prevention in patients meeting JUPITER-type criteria, and management of familial hypercholesterolemia. The 2018 AHA/ACC Cholesterol Guideline classifies rosuvastatin 20–40 mg as high-intensity therapy (≥50% LDL-C reduction) and 5–10 mg as moderate-intensity (30–49% reduction).
Stroke prevention beyond JUPITER population — used in patients with elevated ASCVD risk who fall outside JUPITER inclusion criteria, supported by class-wide data from the Cholesterol Treatment Trialists’ Collaboration. Evidence: high quality (extrapolated from CTT meta-analyses).
Diabetic dyslipidemia without overt ASCVD — preferred high-intensity statin for some patients with renal impairment or polypharmacy because of minimal CYP3A4 metabolism. Evidence: moderate quality.
Non-alcoholic fatty liver disease (NAFLD) with concurrent dyslipidemia — observational data suggest safety and possible hepatic benefit. Evidence: low quality.
Dosing
Doses are organized below by clinical scenario. All regimens are administered orally, once daily, with or without food, at any time of day. Tablets must be swallowed whole; the Ezallor Sprinkle capsule formulation may be opened and sprinkled on soft food per the product label. Reassess LDL-C as early as 4 weeks after initiation or dose change.
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Hyperlipidemia — moderate-intensity goal (LDL-C reduction 30–49%) | 5–10 mg once daily | 5–10 mg once daily | 10 mg/day | Reassess LDL at 4–12 weeks; titrate if goal not reached Suitable for primary prevention with intermediate ASCVD risk |
| Hyperlipidemia — high-intensity goal (LDL-C reduction ≥50%) | 10–20 mg once daily | 20–40 mg once daily | 40 mg/day | 40 mg reserved for patients not at LDL-C goal on 20 mg Standard dose range per FDA label is 5–40 mg/day |
| ASCVD secondary prevention (post-MI, post-stroke, established CAD/PAD) | 20–40 mg once daily | 20–40 mg once daily | 40 mg/day | Aim for ≥50% LDL-C reduction (AHA/ACC) or LDL-C <55 mg/dL (ESC) If <50% reduction at 40 mg, add ezetimibe |
| Primary prevention — JUPITER population (men ≥50, women ≥60, hsCRP ≥2 mg/L, LDL <130) | 20 mg once daily | 20 mg once daily | 20 mg/day (JUPITER-evaluated dose) | JUPITER demonstrated 44% RRR in primary composite endpoint at this dose Confirm baseline ASCVD risk and CV risk factor before initiation |
| Homozygous familial hypercholesterolemia (HoFH) — adults | 20 mg once daily | 20–40 mg once daily | 40 mg/day | Often combined with PCSK9 inhibitor, ezetimibe, or LDL apheresis Mean LDL-C reduction ~22% in HoFH (lower than HeFH due to receptor defect) |
| Homozygous familial hypercholesterolemia (HoFH) — pediatric ≥7 years | 20 mg once daily | 20 mg once daily | 20 mg/day | Per Crestor PI; usually combined with other LDL-lowering therapy Based on placebo-controlled cross-over study (n=14) |
| Heterozygous familial hypercholesterolemia (HeFH) — pediatric 8 to <10 years | 5 mg once daily | 5–10 mg once daily | 10 mg/day | Titrate per LDL-C response and tolerability Growth, weight, and sexual maturation should be monitored |
| Heterozygous familial hypercholesterolemia (HeFH) — pediatric 10–17 years | 5 mg once daily | 5–20 mg once daily | 20 mg/day | Titrate per LDL-C response and tolerability No detectable effect on growth or sexual maturation in 2-year trial |
| Severe hypertriglyceridemia (TG ≥500 mg/dL) | 10 mg once daily | 10–40 mg once daily | 40 mg/day | Modest TG reduction (~25%); often combined with omega-3 or fenofibrate Avoid gemfibrozil combination; fenofibrate preferred when a fibrate is needed |
Population-Specific Adjustments
| Population | Starting Dose | Maximum Dose | Notes |
|---|---|---|---|
| Severe renal impairment (CrCl <30 mL/min/1.73 m², not on hemodialysis) | 5 mg once daily | 10 mg/day | ~3-fold higher plasma exposure; do not exceed 10 mg |
| Asian ancestry (Chinese, Japanese, Filipino, Korean, Vietnamese, Asian-Indian) | 5 mg once daily | Standard 40 mg/day per label, but review risks/benefits if not controlled at 20 mg | ~2-fold higher exposure attributed to OATP1B1 polymorphism prevalence |
| Concomitant cyclosporine | 5 mg once daily | 5 mg/day | ~7-fold increase in rosuvastatin exposure |
| Concomitant gemfibrozil | Avoid combination; if used, 5 mg once daily | 10 mg/day | ~2-fold rise in AUC; markedly elevated myopathy risk |
| Concomitant atazanavir/ritonavir or lopinavir/ritonavir | 5 mg once daily (recommended starting) | 10 mg/day | Significant increase in rosuvastatin exposure |
| Hemodialysis | 5 mg once daily | Per clinical response (usually ≤10 mg) | Steady-state plasma concentrations ~50% greater than in healthy volunteers; hemodialysis does not significantly enhance clearance |
| Mild–moderate hepatic impairment (Child-Pugh A/B) | Standard dosing acceptable | Standard maxima | Cmax ~60–100% higher; monitor LFTs more frequently |
Each dose doubling of rosuvastatin produces approximately 6% additional LDL-C reduction (the “rule of 6” common to all statins). Patients far from goal at 20 mg generally derive more benefit from adding ezetimibe (an additional ~13–20% LDL reduction) than from doubling to 40 mg.
Unlike simvastatin and lovastatin, rosuvastatin can be taken at any time of day because of its 19-hour half-life. AUC does not differ between morning and evening dosing — choose whichever timing best supports adherence.
Pharmacology
Mechanism of Action
Rosuvastatin is a competitive, reversible inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme converting HMG-CoA to mevalonate in hepatic cholesterol biosynthesis. Reduced intracellular cholesterol upregulates LDL receptors on hepatocytes, accelerating clearance of LDL particles from circulation. The net effect is dose-dependent reduction in LDL-C, apolipoprotein B, non-HDL-C, and total cholesterol, with modest reductions in triglycerides and small increases in HDL-C.
Rosuvastatin is more hydrophilic than most other statins, which limits passive entry into peripheral tissues including skeletal muscle and is thought to contribute to its relatively favorable myotoxicity profile. Hepatic uptake is mediated chiefly by the OATP1B1 transporter; this transporter is therefore the dominant determinant of inter-individual exposure and the locus of most clinically meaningful drug interactions. Beyond LDL lowering, rosuvastatin produces dose-dependent reductions in high-sensitivity C-reactive protein (hsCRP), the basis for the JUPITER trial demonstrating cardiovascular benefit in patients with normal LDL-C but elevated hsCRP.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Tmax 3–5 h; absolute bioavailability ~20%; AUC unaffected by food or time of administration | Take with or without food, at any time of day |
| Distribution | Vd ~134 L; protein binding ~88% (mostly albumin); concentrated in hepatocytes via OATP1B1 | Hepatoselective uptake reduces extrahepatic exposure and likely contributes to lower myopathy risk |
| Metabolism | Minimal hepatic metabolism (~10%, mainly CYP2C9 to N-desmethyl rosuvastatin); negligible CYP3A4 involvement | Far fewer CYP-mediated interactions than simvastatin or atorvastatin; OATP1B1 and BCRP inhibitors drive most clinically significant interactions |
| Elimination | ~90% fecal (largely unabsorbed parent drug); after IV dosing, ~28% renal and 72% hepatic clearance; t½ ~19 h | Long half-life supports once-daily dosing at any time; renal clearance necessitates dose reduction in severe CKD |
Side Effects
Adverse-effect frequencies below are taken from the rosuvastatin controlled clinical trials database (n=5,394) and from the major outcomes trials (JUPITER, METEOR), as reported in the Crestor prescribing information. Real-world rates of muscle and gastrointestinal symptoms are often higher than pivotal-trial reports because of selection criteria and the well-described nocebo effect.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| None individually reported at ≥10% in placebo-controlled trials | — | The Crestor PI does not list any single adverse reaction at ≥10% incidence in placebo-controlled trials. Pooled observational data place statin-associated muscle symptoms at 5–10%; see Tier 2 for the specific reactions reported at ≥2% AHA Statin Safety Statement (2019) characterizes RCT myalgia rates as 1–5% and observational rates as 5–10% |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Headache | 3.7% | Generally mild; usually resolves within weeks; rarely dose-limiting |
| Myalgia (without CK elevation) | 3.1% | Most common reason for discontinuation; check baseline TSH and vitamin D if persistent Observational rate is higher than RCT rate |
| Abdominal pain | 2.6% | Usually mild; rule out gallbladder disease if severe or worsening |
| Asthenia / fatigue | 2.5% | Often improves over weeks; rule out hypothyroidism if persistent |
| Nausea | 2.2% | Take with food if bothersome; usually transient |
| New-onset diabetes mellitus (JUPITER) | 2.8% vs 2.3% placebo | HbA1c rose by 0.1% on average; risk concentrated in patients with prediabetes / metabolic syndrome; CV benefit substantially outweighs glycemic risk |
| Asymptomatic ALT/AST elevation >3× ULN | ~1% | Reversible on discontinuation or dose reduction; not predictive of clinical hepatotoxicity |
| Proteinuria (dipstick) and microscopic hematuria | ~1% at 40 mg | Usually transient; not associated with progressive renal dysfunction; reduce dose if persistent |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Rhabdomyolysis with possible acute renal failure | Very rare | Weeks–months; risk highest with interacting drugs and at 40 mg | Stop drug immediately; check CK and renal function; aggressive hydration; avoid all statins until resolved |
| Symptomatic myopathy (CK >10× ULN with muscle symptoms) | Rare | Weeks–months | Discontinue; rechallenge with lower dose or alternate statin only after resolution |
| Immune-mediated necrotizing myopathy (IMNM) | Very rare (~2 per million person-years across statin class) | Months–years; persists or worsens after stopping | Permanent discontinuation; check anti-HMGCR antibody; refer to neurology / rheumatology for immunosuppressive therapy |
| Fatal and non-fatal hepatic failure | Rare (post-marketing) | Weeks–months | Discontinue if ALT/AST >3× ULN with symptoms or jaundice; evaluate for other causes |
| Hypersensitivity (rash, urticaria, angioedema; rarely SJS/TEN, DRESS) | Rare (post-marketing) | Days–weeks | Permanent discontinuation; avoid all statins after anaphylaxis or severe cutaneous reaction |
| Cognitive impairment (memory loss, confusion — usually reversible) | Rare (post-marketing, statin class label) | Days to years; resolution typically within weeks of discontinuation | Trial of discontinuation if temporally related; usually reversible; not a contraindication to future statin therapy |
| Interstitial lung disease | Very rare (post-marketing) | Months–years | Discontinue; pulmonology referral; high-resolution CT chest |
| Thrombocytopenia, peripheral neuropathy (statin class) | Very rare (post-marketing) | Months | Discontinue if temporally related and other causes excluded |
| Reason for Discontinuation | Context | Comment |
|---|---|---|
| Myalgia / muscle symptoms | Most common reason in pooled trials and outcome studies | True drug-attributable rate in blinded N-of-1 designs is much lower than open-label rate |
| Hepatic enzyme increased (ALT/AST >3× ULN) | Frequently asymptomatic | Many cases resolve on dose reduction; rarely indicative of clinical hepatotoxicity |
| Headache | Usually transient | Most resolve within weeks of initiation |
| Nausea / GI intolerance | Usually transient | Often improves with food or evening dosing |
| Hypersensitivity | Permanent discontinuation indicated | Switch class if needed |
Pediatric discontinuation data: in the 2-year open-label HeFH titration trial (n=175), the adverse-event profile in children and adolescents was generally similar to that in adults; no detectable effect on growth, weight, BMI, or sexual maturation was observed.
Most reported muscle symptoms are not drug-attributable when tested in blinded N-of-1 designs. A stepwise approach is recommended: (1) confirm symptoms with a 4–6 week drug holiday; (2) check TSH, vitamin D, and creatinine; (3) if true rechallenge fails on rosuvastatin, try an alternate statin (pravastatin and pitavastatin have low myalgia rates); (4) consider intermittent dosing (e.g., rosuvastatin 5–10 mg every other day or twice weekly); (5) if statin truly intolerated, escalate to ezetimibe ± PCSK9 inhibitor or bempedoic acid.
Drug Interactions
Because rosuvastatin undergoes minimal CYP3A4 metabolism, the classic CYP3A4-driven interactions that complicate simvastatin and atorvastatin are largely absent. The dominant interaction mechanism is inhibition of the hepatic uptake transporters OATP1B1 and BCRP; inhibitors of these transporters raise systemic exposure and amplify myotoxicity risk. The current Crestor PI lists multiple agents with specific dose limits.
Monitoring
-
Lipid Panel
Baseline; reassess as early as 4 weeks; then 4–12 weeks after dose change; then annually
Routine Confirm percent LDL-C reduction (≥50% target for high-intensity, 30–49% for moderate-intensity). Adherence is a more common reason for inadequate response than non-response. -
ALT / AST
Baseline; thereafter only if symptoms
Trigger-based Routine periodic LFTs are no longer recommended. Repeat if patient develops jaundice, fatigue, abdominal pain, dark urine, or unexplained nausea. Discontinue if ALT/AST >3× ULN with symptoms. -
Creatine Kinase (CK)
Baseline only in high-risk patients; otherwise only if symptoms
Trigger-based High-risk = age ≥65, hypothyroidism, renal impairment, prior statin myopathy, Asian ancestry, or interacting drug. Check if patient develops myalgia, weakness, or dark urine. Stop if CK >10× ULN with symptoms. -
HbA1c / Fasting Glucose
Baseline; periodically if at risk for diabetes
Routine Modest excess incidence of new-onset diabetes (mostly in patients with prediabetes). CV benefit greatly outweighs glycemic risk; do not stop the statin if A1c rises into diabetic range. -
Renal Function
Baseline; per overall comorbidity profile
Routine Estimate CrCl/eGFR before initiation and recheck if clinical change. Severe CKD (CrCl <30 mL/min/1.73 m²) requires dose cap at 10 mg/day. Asymptomatic dipstick proteinuria is more common at 40 mg and is not progressive. -
TSH
If unexplained myalgia or rising CK
Trigger-based Unrecognized hypothyroidism is a major contributor to apparent statin intolerance and CK rise; treat the thyroid before declaring statin intolerance. -
Vitamin D (25-OH)
If persistent muscle symptoms
Trigger-based Vitamin D deficiency mimics statin myalgia and is common in this population; replete before considering rechallenge. -
Adherence Check
Every clinical visit
Routine Approximately half of patients discontinue statins within 1 year of initiation. Open, non-judgemental questioning (“How often do you forget?”) yields more accurate information than yes/no adherence questions. -
Pregnancy Status
In females of reproductive potential, periodically
Trigger-based FDA removed the pregnancy contraindication in July 2021. Statins are generally discontinued during planned or confirmed pregnancy unless benefits clearly outweigh risk (e.g., HoFH or established ASCVD). Effective contraception is recommended during therapy.
Contraindications & Cautions
Absolute Contraindications (per current FDA Crestor PI)
- Acute liver failure or decompensated cirrhosis.
- Hypersensitivity to rosuvastatin or any formulation excipient (including any prior statin-induced anaphylaxis, SJS/TEN, or DRESS).
Relative Contraindications (Specialist Input Recommended)
- Pregnancy — although the FDA removed the contraindication in 2021, statins are still typically discontinued during planned or confirmed pregnancy. Continued use is reasonable only in HoFH or established ASCVD where lipid-lowering benefit clearly outweighs theoretical fetal risk; document the explicit risk-benefit discussion.
- Lactation — breastfeeding is not recommended during rosuvastatin therapy; if therapy is required postpartum, use formula.
- Severe renal impairment (CrCl <30 mL/min/1.73 m², not on hemodialysis) — start at 5 mg, do not exceed 10 mg/day.
- History of statin-induced rhabdomyolysis or immune-mediated necrotizing myopathy — IMNM is a permanent contraindication to all statins; uncomplicated SAMS may permit cautious rechallenge with a different statin.
- Concomitant cyclosporine — only the 5 mg/day dose is permissible; consider an alternative statin where possible.
- Active heavy alcohol use — increased risk of hepatotoxicity; address alcohol use first where possible.
Use with Caution
- Asian ancestry — initiate at 5 mg due to ~2-fold higher exposure.
- Age ≥65 years — frailty, polypharmacy, and lower muscle mass raise myopathy risk.
- Hypothyroidism — treat first; untreated hypothyroidism amplifies myopathy risk and elevates CK.
- Concomitant fibrates, niacin (≥1 g/day), colchicine, or daptomycin — additive myotoxicity; counsel on muscle symptoms.
- Diabetes risk factors (prediabetes, metabolic syndrome) — small excess diabetes incidence; CV benefit nonetheless outweighs risk.
- Pediatric patients <7 years (HoFH) or <8 years (HeFH) — efficacy and safety not established below these ages.
The FDA requested removal of the contraindication against statin use in pregnancy from the labeling of all statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin). The change does not endorse routine use; it allows individualized risk-benefit decisions, particularly for women with HoFH, established ASCVD, or very high CV risk.
Most patients should still discontinue statins on confirmation of pregnancy. Lactation remains a reason to defer therapy because of unknown infant exposure and theoretical risk; patients who require ongoing statin therapy postpartum should not breastfeed.
All HMG-CoA reductase inhibitors carry a class-wide warning regarding rare but serious myopathy and rhabdomyolysis. Risk rises with higher doses, advancing age (≥65 years), uncontrolled hypothyroidism, renal impairment, female sex, low body weight, Asian ancestry, and concomitant interacting drugs (especially cyclosporine, gemfibrozil, certain antivirals, niacin, and fibrates).
Counsel every patient to promptly report unexplained muscle pain, tenderness, weakness, or dark urine. Discontinue immediately if rhabdomyolysis is suspected or if CK rises >10× ULN with symptoms. Temporarily withhold rosuvastatin in any patient with an acute serious condition predisposing to rhabdomyolysis (sepsis, hypotension, dehydration, major surgery, severe metabolic or electrolyte disorder, uncontrolled seizures).
Patient Counselling
Purpose of Therapy
Rosuvastatin lowers LDL (“bad”) cholesterol by reducing the liver’s production of cholesterol. Lower LDL means less plaque buildup inside arteries, which reduces the chance of heart attacks, strokes, and the need for procedures such as stents or bypass surgery. The benefit accumulates over years — most patients are taking it for prevention rather than for symptom relief, so they may not “feel” anything different. Lifestyle measures (diet, exercise, weight control, smoking cessation) act on the same arteries and add to the benefit.
How to Take
Take one tablet once a day, with or without food, at any time of day. Choose a time that fits the daily routine — morning with breakfast or evening with dinner are both fine. Swallow tablets whole. Do not take a double dose if a dose is missed; resume at the next regular dose. Antacids that contain aluminum or magnesium should be taken at least 2 hours after the rosuvastatin dose. Do not stop the medicine without speaking to the prescriber, even if cholesterol numbers look good — stopping is when the protection fades.
Sources
- CRESTOR (rosuvastatin calcium) US Prescribing Information. AstraZeneca Pharmaceuticals LP; revised 2024. Accessed via FDA Drugs@FDA. accessdata.fda.gov/drugsatfda_docs/label/2024/021366s046lbl.pdf Authoritative source for FDA-approved indications, dosing, contraindications, and adverse-reaction frequencies cited in this monograph.
- EZALLOR SPRINKLE (rosuvastatin) Prescribing Information. Sun Pharmaceutical Industries; revised 2024. accessdata.fda.gov/drugsatfda_docs/label/2024/208647s013lbl.pdf Sprinkle capsule formulation labeling; aligned with Crestor on indications, dosing limits, and contraindications.
- FDA Drug Safety Communication: FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy. July 20, 2021. fda.gov The 2021 labeling change underlying current pregnancy guidance.
- Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein (JUPITER). N Engl J Med. 2008;359(21):2195-2207. doi:10.1056/NEJMoa0807646. doi.org/10.1056/NEJMoa0807646 Pivotal primary-prevention trial supporting the FDA primary-prevention indication; HR 0.56 for the primary composite endpoint (44% relative risk reduction).
- Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol. 2003;92(2):152-160. doi:10.1016/s0002-9149(03)00530-7 Head-to-head dose-comparison data establishing rosuvastatin’s potency advantage on a milligram-for-milligram basis across the 10–40 mg range.
- Crouse JR III, Raichlen JS, Riley WA, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals (METEOR). JAMA. 2007;297(12):1344-1353. doi:10.1001/jama.297.12.1344 Imaging trial supporting the slowing-of-atherosclerosis indication; source for the 5.6% vs 2.8% adverse-event discontinuation rates cited in this monograph.
- Nicholls SJ, Brandrup-Wognsen G, Palmer M, et al. Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol. 2010;105(1):69-76. doi:10.1016/j.amjcard.2009.08.651 Pooled individual-patient meta-analysis underpinning the AHA/ACC 2018 statin-intensity classification used here.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625 Primary US guideline; classifies rosuvastatin 20–40 mg as high-intensity therapy and 5–10 mg as moderate-intensity for primary and secondary prevention.
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455 European framework with lower LDL-C targets (e.g., <55 mg/dL in very-high-risk patients) supporting high-intensity rosuvastatin dosing.
- Newman CB, Preiss D, Tobert JA, et al. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2019;39(2):e38-e81. doi:10.1161/ATV.0000000000000073 Comprehensive class-wide safety review used here for myopathy framing, observational vs RCT muscle-symptom rates, and diabetes risk discussion.
- Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397-1405. doi:10.1016/S0140-6736(14)61368-4 Class-wide meta-analysis underlying “lower is better” LDL-C principle and the magnitude-of-benefit framing in this monograph.
- Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19(1):117-125. doi:10.1111/j.1472-8206.2004.00299.x Comparative pharmacology framework distinguishing rosuvastatin from CYP3A4-metabolized statins.
- Lee E, Ryan S, Birmingham B, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005;78(4):330-341. doi:10.1016/j.clpt.2005.06.013 Source for the ~2-fold AUC increase observed in Asian-ancestry patients; basis for the 5 mg starting dose.
- Simonson SG, Raza A, Martin PD, et al. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clin Pharmacol Ther. 2004;76(2):167-177. doi:10.1016/j.clpt.2004.03.010 Quantifies the ~7-fold AUC rise driving the 5 mg dose cap with cyclosporine.
- Martin PD, Warwick MJ, Dane AL, et al. Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin Ther. 2003;25(11):2822-2835. doi:10.1016/s0149-2918(03)80336-3 Primary pharmacokinetic study confirming ~20% bioavailability, ~10% metabolism, and predominantly fecal excretion.