ROSUVASTATIN ZINC
Clinical safety rating: avoid
Not significantly metabolized by CYP450 enzymes fewer interactions Can cause myopathy and rhabdomyolysis.
Rosuvastatin zinc is a HMG-CoA reductase inhibitor that competitively inhibits the conversion of HMG-CoA to mevalonate, reducing hepatic cholesterol synthesis, increasing LDL receptor expression, and lowering plasma LDL-C and triglycerides.
| Metabolism | Limited hepatic metabolism; primarily metabolized by CYP2C9 (minor role of CYP2C19 and CYP3A4). Approximately 10% is metabolized. Majority excreted unchanged in feces (90%) and urine (10% as parent drug). |
| Excretion | Primarily biliary/fecal: approximately 90% of the dose is eliminated unchanged in feces via biliary secretion. Renal excretion accounts for about 10%, mainly as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 19 hours (range 13–20 hours). This supports once-daily dosing, with steady-state reached within 5 days. |
| Protein binding | Approximately 88% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 134 L (1.9 L/kg for a 70 kg individual), indicating extensive extravascular distribution, particularly into hepatic tissue. |
| Bioavailability | Oral bioavailability is approximately 20% (range 18–22%), with food reducing the rate but not extent of absorption. |
| Onset of Action | Oral: Onset of lipid-lowering effect is observed within 1 week, with maximal effect by 4 weeks. |
| Duration of Action | Duration of action is about 24 hours, consistent with once-daily dosing, due to sustained HMG-CoA reductase inhibition throughout the dosing interval. |
| Molecular Weight | 481.6 Da (as zinc salt, approximate; rosuvastatin base MW = 481.6) |
Oral, 5-40 mg once daily. Starting dose 10-20 mg; titrate based on LDL-C response. Maximum dose 40 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-80 mL/min: no adjustment. CrCl <30 mL/min (not on hemodialysis): maximum dose 10 mg once daily. Hemodialysis: contraindicated. |
| Liver impairment | Child-Pugh class A: no adjustment (maximum 20 mg). Child-Pugh class B: contraindicated. Child-Pugh class C: contraindicated. |
| Pediatric use | Children ≥8 years: 5-20 mg once daily; start at 5 mg. Heterozygous familial hypercholesterolemia: 5-20 mg. Maximum 20 mg. |
| Geriatric use | Start at 5 mg once daily; titrate cautiously. Maximum 20 mg due to increased systemic exposure. |
| 1st trimester | Contraindicated due to risk of fetal skeletal abnormalities; crosses placenta. |
| 2nd trimester | Contraindicated; inhibits cholesterol synthesis essential for fetal development. |
| 3rd trimester | Contraindicated; potential for neonatal toxicity and developmental effects. |
Clinical note
Not significantly metabolized by CYP450 enzymes fewer interactions Can cause myopathy and rhabdomyolysis.
| FDA category | Contraindicated |
| Placental transfer | Rosuvastatin crosses the placenta; animal studies show fetal toxicity. Human data limited but suggests transfer. |
| Breastfeeding | Excreted in human milk; potential risk of serious adverse reactions in nursing infants. Use is not recommended during breastfeeding. |
■ FDA Black Box Warning
Rosuvastatin may cause skeletal muscle toxicity (myopathy, rhabdomyolysis) leading to acute renal failure, especially at higher doses or with concomitant use of certain drugs. Therapy should be discontinued if CK levels are markedly elevated or if muscle symptoms occur.
| Common Effects | Nausea Stomach pain Constipation Muscle pain Weakness Dizziness Increased glucose level in blood |
| Serious Effects |
Active liver diseaseUnexplained persistent elevations of serum transaminasesHypersensitivity to rosuvastatin or any componentPregnancyLactationConcomitant use of cyclosporine
| Precautions | Myopathy and rhabdomyolysis risk; monitor CK levels and discontinue if symptoms develop, Renal impairment; dose adjustment required for eGFR <30 mL/min/1.73m², Hepatic impairment; contraindicated in active liver disease or unexplained transaminase elevations, Increased risk of muscle toxicity with concomitant use of gemfibrozil, cyclosporine, protease inhibitors, or certain antifungal agents, May cause immune-mediated necrotizing myopathy (IMNM), Monitor for proteinuria (dose-dependent) and serum glucose (increased HbA1c and fasting glucose) |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | FDA Pregnancy Category X. Statins are contraindicated in pregnancy. First trimester: Risk of fetal skeletal and cardiac anomalies based on animal studies. Second and third trimesters: Reduced fetal mevalonate synthesis may impair fetal development. Absolute contraindication throughout pregnancy. |
| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST) prior to and during therapy. Assess for myopathy symptoms (muscle pain, tenderness). Fetal monitoring via ultrasound if inadvertent exposure occurs. |
| Fertility Effects | No specific human fertility data; animal studies show no impairment of fertility. Theoretical reduction in cholesterol synthesis may affect steroidogenesis but clinical significance unclear. |
| Food/Dietary | Grapefruit juice may increase rosuvastatin exposure; limit to small amounts or avoid. High-fat meals do not affect absorption significantly. Avoid excessive alcohol. |
| Clinical Pearls | Rosuvastatin zinc is a statin with high potency and a long half-life (19 h). Monitor for myopathy, especially with concomitant use of fibrates or niacin. Renal impairment increases exposure; adjust dose in severe CKD. Avoid in active liver disease. May increase HbA1c and fasting glucose. |
| Patient Advice | Take once daily, with or without food, at the same time each day. · Report unexplained muscle pain, tenderness, or weakness, especially with fever or malaise. · Avoid grapefruit juice as it may increase rosuvastatin levels. · Maintain a heart-healthy diet low in saturated fats and cholesterol. · Limit alcohol consumption to reduce liver stress. |