ROSUVASTATIN CALCIUM
Clinical safety rating: avoid
Contraindicated (not allowed)
Rosuvastatin is a competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. This reduces hepatic cholesterol synthesis, upregulates LDL receptors, and enhances clearance of LDL from plasma.
| Metabolism | Minimal metabolism (<10%) via CYP2C9; predominantly excreted unchanged in feces (90%) and urine (10%). Not significantly metabolized by CYP3A4. |
| Excretion | Approximately 90% of the absorbed dose is excreted in feces via biliary elimination, with the remaining 10% excreted renally as unchanged drug and metabolites. Unchanged rosuvastatin accounts for about 5% of the dose in urine. |
| Half-life | Terminal elimination half-life is approximately 19 hours, which supports once-daily dosing and allows for sustained HMG-CoA reductase inhibition. |
| Protein binding | Approximately 88% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is about 134 L (1.96 L/kg for a 70 kg individual), indicating extensive distribution into extravascular tissues. |
| Bioavailability | Oral bioavailability is approximately 20%, with food decreasing the rate but not the extent of absorption. |
| Onset of Action | Oral: Significant LDL-C reduction is observed within 1 week of starting therapy, with maximum effect achieved by 4 weeks. |
| Duration of Action | Duration of LDL-C lowering persists for the dosing interval (24 hours). After discontinuation, effects on lipid levels gradually return to baseline over several weeks. |
| Molecular Weight | 500.58 Da (as calcium salt; free acid: 481.54 Da) |
Oral, 5-40 mg once daily, starting at 5-10 mg, titrated based on LDL-C response, maximum 40 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: initiate at 5 mg, maximum 20 mg/day. GFR <30 mL/min (not on hemodialysis): contraindicated. |
| Liver impairment | Child-Pugh class A: no adjustment. Child-Pugh class B: use with caution, maximum 20 mg/day. Child-Pugh class C: contraindicated. |
| Pediatric use | Age 8-17 years: heterozygous familial hypercholesterolemia, weight <50 kg: 5-20 mg once daily; weight ≥50 kg: 5-40 mg once daily. Initiate at 5 mg, maximum as per adult. |
| Geriatric use | No specific adjustment, but start at lower end of dosing range (5 mg) due to increased risk of myopathy and renal impairment; monitor renal function and consider maximum 20 mg/day if age >65 years without significant renal impairment. |
| 1st trimester | Contraindicated. Statins are generally avoided in pregnancy due to potential for fetal harm. Case reports suggest possible skeletal abnormalities. The drug may reduce synthesis of cholesterol and other mevalonate-derived substances essential for fetal development. |
| 2nd trimester | Contraindicated. Similar risks as first trimester. Lipid-lowering effects can persist and may affect fetal development. |
| 3rd trimester | Contraindicated. Potential for adverse effects on fetal development, including possible neurological and skeletal anomalies. |
Clinical note
Not significantly metabolized by CYP450 enzymes fewer interactions Can cause myopathy and rhabdomyolysis.
| Placental transfer | Rosuvastatin is highly bound to plasma proteins (88%) and is a substrate for OATP1B1, limiting placental transfer. However, animal studies show fetal exposure, and human placental perfusion studies demonstrate transfer with reduction in fetal drug concentrations due to efflux transporters. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warnings.
| Common Effects | Muscle pain Weakness Headache Abdominal pain Dizziness Joint pain Nausea |
| Serious Effects |
Active liver disease or unexplained persistent elevations of serum transaminasesHypersensitivity to rosuvastatin or any component of the formulationPregnancyLactationConcomitant use with cyclosporine
| Precautions | Risk of myopathy/rhabdomyolysis, especially with high doses or concomitant use of cyclosporine, fibrates, or certain CYP inhibitors, Hepatic enzyme elevations: monitor liver function tests before and during therapy, Increased HbA1c and fasting glucose levels (new-onset diabetes mellitus), Avoid in Asian patients at lower doses due to increased plasma exposure, Contraindicated in active liver disease or unexplained persistent transaminase elevations |
| Food/Dietary |
Loading safety data…
| Rosuvastatin is excreted in human milk at low levels. The clinical significance is unknown, but due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy. If unavoidable, use the lowest effective dose and monitor infant for adverse effects. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Rosuvastatin is contraindicated in pregnancy. First trimester: Potential for fetal developmental abnormalities based on animal studies and limited human data; inhibits HMG-CoA reductase critical for fetal sterol synthesis. Second and third trimesters: Continued risk of fetal toxicity; associated with decreased fetal cholesterol synthesis, potential for skeletal and organ malformations. All trimesters: Category X; avoid use due to risk of fetal harm. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST) periodically; assess renal function (serum creatinine); check creatine kinase (CK) if muscle symptoms occur. In pregnancy, perform fetal ultrasound if inadvertent exposure. No routine fetal monitoring specific to rosuvastatin. |
| Fertility Effects | No specific human studies on fertility. In animal studies, no adverse effects on fertility at doses up to 25 mg/kg (approx 200 times human exposure). Theoretical concern: Lipid-lowering may affect steroid hormone synthesis, but no clinical evidence of impaired fertility. |
| Grapefruit juice increases rosuvastatin exposure and should be avoided. High-fat meals may slightly reduce absorption but not clinically significant. Excessive alcohol consumption may increase risk of liver damage. No other specific food restrictions. |
| Clinical Pearls | Rosuvastatin is a high-potency statin with a long half-life (~19 h), allowing once-daily dosing. It is primarily excreted unchanged in feces, with minimal hepatic metabolism, making it less prone to CYP3A4 drug interactions. However, avoid grapefruit juice as it may increase exposure. Monitor renal function in patients predisposed to renal impairment. Do not exceed 40 mg daily; higher doses increase risk of myopathy, especially in Asians and those with predisposing factors. Rosuvastatin reduces LDL-C by up to 55% and also modestly raises HDL-C. It has anti-inflammatory effects (reduces hs-CRP). Use with caution in patients on cyclosporine or protease inhibitors. |
| Patient Advice | Take rosuvastatin exactly as prescribed, usually once daily, with or without food. · Do not crush or chew tablets; swallow whole. · Notify your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise. · Avoid consuming grapefruit or grapefruit juice while on this medication. · Maintain a heart-healthy diet low in saturated fat and cholesterol to enhance effectiveness. · Inform your healthcare provider about all medications you take, including over-the-counter drugs and supplements. · Women of childbearing age must use effective contraception; do not use if pregnant or breastfeeding. · Regular monitoring of liver function and lipid levels is required. · Do not stop taking this medication without consulting your doctor. |