CRESTOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CRESTOR (CRESTOR).
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to increased hepatic LDL receptor expression and reduced plasma LDL cholesterol.
| Metabolism | Primarily hepatic via CYP2C9 and to a lesser extent CYP2C19; not extensively metabolized; minimal metabolism by CYP3A4. |
| Excretion | Approximately 90% of rosuvastatin is eliminated in feces (as unchanged drug and metabolites), and about 10% is excreted in urine (mainly as unchanged drug). Biliary excretion is the primary route for elimination of metabolites. |
| Half-life | The terminal elimination half-life is approximately 19 hours (range 13–20 hours). This long half-life allows once-daily dosing and provides sustained HMG-CoA reductase inhibition. |
| Protein binding | Approximately 88% bound to plasma proteins, mainly albumin. |
| Volume of Distribution | The volume of distribution is approximately 134 L (about 1.9 L/kg for a 70 kg individual), indicating extensive distribution into extravascular tissues. |
| Bioavailability | Absolute oral bioavailability is approximately 20%. Food does not affect the extent of absorption (AUC) but may delay the rate (Tmax) by about 1 hour. |
| Onset of Action | Significant reduction in LDL-C is observed within 1 week of oral administration; maximal effect is achieved by 2–4 weeks. |
| Duration of Action | The duration of action is approximately 24 hours based on once-daily dosing, with sustained LDL-C reduction throughout the dosing interval due to the long half-life. |
| Molecular Weight | 481.54 |
| Action Class | HMG CoA inhibitors (statins) |
| Brand Substitutes | Unizuva 10mg Tablet, Lipirose 10 Tablet, Consivas 10 Tablet, Rosufit 10 Tablet, Jupiros 10 Tablet, Crevast 20 Tablet, Consivas 20 Tablet, Lipirose 20 Tablet, Rovio 20 Tablet, Rosukem 20 Tablet, Rosys 5 Tablet, Rosufit 5 Tablet, Lipirose 5 Tablet, Jupiros 5 Tablet, Bestor 5 Tablet, Gloristat 40 Tablet, Razel 40 Tablet, Rosycap 40 Tablet, Rosukem 40 Tablet, Jupiros 40 Tablet |
Oral, 5-40 mg once daily. Initial dose typically 10-20 mg; max 40 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: maximum dose 10 mg once daily. CrCl ≥30 mL/min: no adjustment. |
| Liver impairment | Contraindicated in active liver disease or unexplained transaminase elevations. Child-Pugh Class A: no dose adjustment; Class B: use with caution, maximum 10 mg once daily; Class C: no data. |
| Pediatric use | Children 8-17 years: 5-10 mg once daily initially, max 20 mg once daily. Titrate based on LDL-C goal. |
| Geriatric use | No specific dose adjustment typically required; start at lower end of dosing range due to increased risk of myopathy. Maximum 20 mg once daily in patients >65 years. |
| 1st trimester | Contraindicated due to risk of fetal harm; animal studies show teratogenicity. Should not be used in pregnancy. |
| 2nd trimester | Contraindicated; crosses placenta and may impair fetal development. Avoid use. |
| 3rd trimester | Contraindicated; may cause fetal toxicity, including musculoskeletal abnormalities. Discontinue if pregnancy occurs. |
Clinical note
Comprehensive clinical and safety monograph for CRESTOR (CRESTOR).
| Placental transfer | Rosuvastatin crosses the placenta in animals and humans; detected in fetal plasma. |
| Breastfeeding | Excreted in human milk at low levels; however, due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Active liver disease or unexplained persistent elevations of serum transaminasesHypersensitivity to rosuvastatin or any component of the formulationPregnancyLactationConcurrent use with cyclosporine
| Precautions | Myopathy/rhabdomyolysis risk, especially with higher doses and concomitant use of cyclosporine, gemfibrozil, or certain protease inhibitors, Hepatic enzyme elevations; monitor liver function, Increased risk of diabetes mellitus (HbA1c and fasting glucose elevations), Severe hypersensitivity reactions (e.g., angioedema, Stevens-Johnson syndrome) |
| Food/Dietary | Grapefruit juice may increase rosuvastatin levels; avoid large quantities. High-fat meals do not significantly affect absorption. Recommend diet low in saturated fat and cholesterol. |
Loading safety data…
| Lactation Rating |
| L3 - Moderately Safe (but caution advised) |
| Teratogenic Risk | Pregnancy Category X. Contraindicated in pregnancy. Rosuvastatin inhibits HMG-CoA reductase, essential for fetal cholesterol synthesis. First trimester: potential for congenital anomalies (CNS, limb defects) based on animal studies and limited human data. Second/third trimester: risk of fetal toxicity, reduced birth weight. Use only if no alternative and patient is not of childbearing potential. |
| Fetal Monitoring | Monitor lipid panels. If inadvertent exposure during pregnancy, perform fetal ultrasound for structural anomalies. Monitor maternal liver function tests and creatine kinase. Assess for myopathy symptoms. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies showed no impairment of fertility. No specific FDA labeling on human reproductive effects. |
| Clinical Pearls | Rosuvastatin is not significantly metabolized by CYP3A4, reducing risk of many drug-drug interactions. Monitor for new-onset diabetes, especially in patients with risk factors. Avoid in severe renal impairment (CrCl <30 mL/min). Start at 5 mg in Asian patients due to increased systemic exposure. Obtain lipid panel at baseline and after 4 weeks of therapy. |
| Patient Advice | Take at any time of day, with or without food. · Avoid grapefruit juice as it may increase side effects. · Report unexplained muscle pain, tenderness, or weakness (especially if accompanied by fever or dark urine). · Do not take with high-dose vitamin niacin or fibrates unless directed by your doctor. · Maintain a heart-healthy diet low in saturated fat and cholesterol. · Regular exercise and weight control are important. · Alcohol consumption should be limited. |