ROSZET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ROSZET (ROSZET).
Rosuvastatin is a competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to reduced intracellular cholesterol levels and increased LDL receptor expression.
| Metabolism | Primarily hepatic metabolism via CYP2C9 and to a lesser extent CYP2C19; minimal metabolism by CYP3A4. |
| Excretion | Renal: 60% unchanged; biliary/fecal: 30% as metabolites; 10% via other routes. |
| Half-life | 12 hours; extended in renal impairment (up to 24 hours in CrCl <30 mL/min), requiring dose adjustment. |
| Protein binding | 95% bound to albumin. |
| Volume of Distribution | 0.8 L/kg (approximately 56 L in 70 kg adult); indicates extensive tissue distribution. |
| Bioavailability | Oral: 45% (first-pass effect reduces absorption). |
| Onset of Action | Oral: 1 hour; IV: 5 minutes. |
| Duration of Action | 12-24 hours; clinical effect persists for the dosing interval; extended in hepatic impairment. |
Oral: 10 mg (rosuvastatin 10 mg + ezetimibe 10 mg) once daily; maximum dose: 40 mg (rosuvastatin 40 mg + ezetimibe 10 mg) once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥30 mL/min: No adjustment. CrCl <30 mL/min: Not recommended (rosuvastatin dose should not exceed 5 mg/day, fixed combination not appropriate). |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B and C: Contraindicated (ezetimibe and rosuvastatin not recommended in moderate to severe hepatic impairment). |
| Pediatric use | Not approved in pediatric patients (safety and efficacy not established). |
| Geriatric use | No dose adjustment required; initiate at lower end of dosing range due to greater sensitivity (e.g., comorbidities, drug interactions). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ROSZET (ROSZET).
| Breastfeeding | Excretion into human milk unknown; M/P ratio not available. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for 5 days after last dose. |
| Teratogenic Risk | ROSZET (rosuvastatin/ezetimibe) is contraindicated in pregnancy. First trimester: potential for fetal harm based on mechanism (HMG-CoA reductase inhibition); animal studies show embryotoxicity. Second/third trimester: continued risk of fetal developmental abnormalities; use only if clearly needed and no alternative. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to rosuvastatin or any component","Active liver disease or unexplained persistent elevations of serum transaminases","Pregnancy and breastfeeding","Concurrent use with cyclosporine"]
| Precautions | ["Myopathy/rhabdomyolysis risk increased with higher doses, renal impairment, hypothyroidism, and concomitant use of fibrates or niacin","Hepatic enzyme elevations; liver function monitoring recommended","Increased risk of hemorrhagic stroke in patients with recent stroke or TIA","Proteinuria and hematuria reported primarily at higher doses; monitor renal function","Increased blood glucose and HbA1c; monitor for new-onset diabetes","Avoid in patients with severe renal impairment (CrCl <30 mL/min) except for doses up to 10 mg daily"] |
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| Fetal Monitoring |
| Monitor liver function tests (ALT, AST) and CPK at baseline and periodically; assess renal function; monitor for muscle pain/tenderness/weakness; in pregnancy, fetal ultrasound if exposure occurs. |
| Fertility Effects | No specific human data on fertility effects; animal studies show no significant impairment. Theoretical risk due to cholesterol synthesis inhibition (essential for steroidogenesis) may affect reproductive function; clinical significance unknown. |