Rosuvastatin

# Rosuvastatin ## Overview - **Classification**: HMG-CoA reductase inhibitor (statin) - **Mechanism**: Competitively inhibits HMG-CoA reductase, a rate-limiting enzyme in cholesterol synthesis, primarily in the liver. This increases hepatic LDL receptors, leading to reduced plasma LDL-C. ## Primary Indications 1. **Primary Hyperlipidemia/Mixed Dyslipidemia** - Reduces elevated total cholesterol, LDL-C, ApoB, non-HDL-C, and triglycerides. 2. **Homozygous Familial Hypercholesterolemia (HoFH)** - Adjunct to other lipid-lowering treatments or alone if other treatments are unavailable. 3. **Primary Prevention of Cardiovascular Disease (CVD)** - In individuals at increased risk, without clinically evident coronary heart disease. 4. **Hypertriglyceridemia** - As an adjunct to diet in patients with hypertriglyceridemia. ## Adult Dosing ### Standard Dosing **Primary Hyperlipidemia/Mixed Dyslipidemia & Primary Prevention of CVD** - **Dose**: **5-40 mg** - **Frequency**: Once daily - **Route**: Oral - **Special Considerations**: Initiate with **10 mg** for most patients. Consider **5 mg** for Asian patients or those with risk factors for myopathy. Max **40 mg** daily. **Homozygous Familial Hypercholesterolemia (HoFH)** - **Dose**: **20 mg** - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **40 mg** daily ### Dose Adjustments - **Renal Impairment**: - **CrCl 30-60 mL/min**: No initial adjustment, but consider lower starting dose (**5 mg**). Max **40 mg**. - **CrCl <30 mL/min (non-dialysis)**: Initiate with **5 mg** once daily. Max dose **10 mg** once daily. - **End-stage renal disease on Hemodialysis**: Not recommended due to lack of data. - **Hepatic Impairment**: - **Child-Pugh A or B**: No adjustment needed. - **Child-Pugh C (severe)**: Contraindicated. - **Elderly Patients**: No specific adjustment, but consider starting with **5 mg** due to potential increased risk of myopathy. ## Pediatric Dosing ### Neonates (0-28 days) - Not indicated. ### Infants (1-12 months) - Not indicated. ### Children (1-12 years) **Heterozygous Familial Hypercholesterolemia (HeFH)** - **Age 6 to <10 years**: - **Dose**: **5-10 mg** - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **10 mg** daily - **Special Notes**: Initiate with **5 mg**. - **Age 10-17 years**: - **Dose**: **5-20 mg** - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **20 mg** daily - **Special Notes**: Initiate with **5 mg**. **Homozygous Familial Hypercholesterolemia (HoFH)** - **Age 7 to <18 years**: - **Dose**: **20 mg** - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **20 mg** daily (higher doses up to **40 mg** may be used under specialist supervision). - **Special Notes**: Initiated by a specialist. ### Adolescents (13-18 years) - **HeFH**: Dosing as per children 10-17 years: **5-20 mg** once daily (max **20 mg**). - **HoFH**: Dosing as per children 7-17 years: **20 mg** once daily (max **20 mg**, potentially up to **40 mg** with specialist guidance). - **Special Considerations**: Females of child-bearing potential must use effective contraception due to teratogenicity risk. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to rosuvastatin or any component. - **Absolute**: Active liver disease, including unexplained persistent elevated serum transaminases. - **Absolute**: Pregnancy and lactation. - **Absolute**: Co-administration with cyclosporine. - **Absolute**: Severe renal impairment (CrCl <30 mL/min) with concurrent cyclosporine use. ### Common Adverse Effects - **Common (1-10%)**: Headache, myalgia, asthenia, nausea, constipation, abdominal pain. - **Serious but Rare**: Myopathy/rhabdomyolysis (potentially leading to renal failure), hepatotoxicity (elevated LFTs), new-onset diabetes mellitus, interstitial lung disease, immune-mediated necrotizing myopathy. ### Key Drug Interactions - **Cyclosporine**: Greatly increases rosuvastatin exposure; **contraindicated**. - **Gemfibrozil**: Increases rosuvastatin levels; avoid co-administration. If used, limit rosuvastatin to **5 mg** once daily. - **Warfarin**: May potentiate anticoagulant effect; monitor INR closely at initiation/dose change/discontinuation. - **Select Protease Inhibitors (e.g., Atazanavir/Ritonavir)**: Significantly increase rosuvastatin levels; limit rosuvastatin to **10 mg** once daily. - **Niacin (lipid-lowering doses)**: Increased risk of myopathy; use with caution. - **Colchicine**: Increased risk of myopathy. ## Monitoring & Follow-up - **Before Treatment**: Fasting lipid panel, LFTs (ALT, AST), CK (creatine kinase) if patient reports muscle symptoms. - **During Treatment**: - Lipid panel: 4-12 weeks after initiation/dose change, then every 3-12 months. - LFTs: Not routinely recommended unless clinically indicated (e.g., symptoms of liver injury). - CK: Measure if patient develops muscle pain, tenderness, or weakness. - **Clinical Signs**: Muscle pain, weakness, dark urine, unexplained fatigue, yellowing skin/eyes, severe abdominal pain. ## Clinical Pearls - 💡 **Tip 1**: Can be taken at any time of day, with or without food. - 💡 **Tip 2**: Counsel patients to report unexplained muscle pain, tenderness, or weakness immediately. - 💡 **Tip 3**: Emphasize lifestyle modifications (diet, exercise, weight management) as foundational therapy. - 💡 **Tip 4**: Consider a lower starting dose (**5 mg**) for Asian patients due to higher systemic exposure. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.