Creston

• Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial): To reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides and to increase HDL cholesterol.
• Mixed Dyslipidemia: For patients with combined elevations of cholesterol and triglycerides.
• Homozygous Familial Hypercholesterolemia: Adjunct to other lipid-lowering treatments in patients with homozygous familial hypercholesterolemia.
• Prevention of Cardiovascular Disease:
• Primary prevention in patients at high risk of cardiovascular events (e.g., with multiple risk factors).
• Secondary prevention after myocardial infarction or in established coronary heart disease.
• Important Off-label/Clinically accepted uses:
• Treatment of hypertriglyceridemia in some cases.
• Possible use in patients with chronic kidney disease to reduce cardiovascular risk (based on guideline recommendations).

• Adults:
• Initial dose: 10 mg once daily, may be started at 5 mg in patients at increased risk of myopathy (e.g., Asian descent, severe renal impairment).
• Maintenance dose: 10-40 mg once daily depending on LDL cholesterol lowering response and patient tolerance.
• Maximum dose: 40 mg/day (due to increased risk of myopathy/rhabdomyolysis at higher doses).
• Elderly:
• Start with 5 mg daily; monitor closely due to increased risk of adverse effects.
• Pediatric (Children 7-17 years) with heterozygous familial hypercholesterolemia:
• Starting dose: 5 mg once daily.
• Max dose: 20 mg daily.
• Renal Impairment:
• For patients with severe renal impairment (creatinine clearance <30 mL/min), start at 5 mg and do not exceed 10 mg daily.
• Hepatic Impairment:
• Use with caution; contraindicated in active liver disease or unexplained persistent elevations of liver enzymes.
• Administration:
• Oral, once daily, with or without food.
• Taken preferably at the same time each day.

Rosuvastatin calcium is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. By inhibiting this enzyme, rosuvastatin reduces the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol synthesis. This leads to upregulation of LDL receptors on hepatocyte surfaces, increasing clearance of LDL cholesterol from the bloodstream, thereby lowering plasma LDL cholesterol and total cholesterol levels. Additionally, it modestly reduces triglycerides and increases HDL cholesterol, contributing to improved lipid profiles and reduced cardiovascular risk.

• Absorption:
• Oral bioavailability approximately 20%.
• Peak plasma concentration (Tmax) occurs 3–5 hours post-dose.
• Distribution:
• Volume of distribution ~134 L.
• Plasma protein binding ~88%.
• Metabolism:
• Limited metabolism primarily via CYP2C9, minor via CYP2C19; majority excreted unchanged.
• Elimination:
• Half-life approximately 19 hours, allowing once-daily dosing.
• Excreted mainly unchanged in feces (~90%) and less than 10% in urine.
• Steady state: Achieved within 5 days of daily dosing.

• Pregnancy:
• FDA Pregnancy Category X (contraindicated).
• Statins, including rosuvastatin, are contraindicated in pregnancy due to potential teratogenic effects and cholesterol’s critical role in fetal development.
• Lactation:
• Excretion into human milk unknown; animal studies show low levels.
• Use during breastfeeding is not recommended due to potential risk to the infant.
• Women should avoid breastfeeding while on rosuvastatin.

• Primary Class: HMG-CoA Reductase Inhibitor (Statin)
• Subclass: Lipid-lowering agent

• Hypersensitivity to rosuvastatin or any component of the formulation.
• Active liver disease or unexplained persistent elevations of serum transaminases.
• Pregnancy and lactation.
• Concomitant use with cyclosporine (due to increased rosuvastatin plasma concentrations).
• Patients with severe renal impairment when dosed above recommended amounts.

• Myopathy and Rhabdomyolysis: Increased risk especially at higher doses (>20 mg), with renal impairment, in elderly, or with interacting drugs. Monitor for muscle pain, tenderness, or weakness.
• Liver enzyme elevations: Monitor liver function tests before starting and periodically thereafter. Discontinue if persistent elevations occur.
• Renal impairment: Use lower doses; monitor renal function.
• Asian patients: Increased rosuvastatin plasma concentrations observed; start at lower dose (5 mg).
• New onset diabetes: Slight increased risk reported; monitor blood glucose in at-risk patients.
• Cognitive effects: Rare reports of memory loss or confusion; discontinue if symptoms occur.
• Avoid excessive alcohol consumption to reduce hepatotoxicity risk.

• Common:
• Headache, myalgia, abdominal pain, nausea, constipation, weakness.
• Serious but rare:
• Rhabdomyolysis (severe muscle breakdown), myopathy, hepatotoxicity, hypersensitivity reactions (rash, angioedema).
• Others:
• Increased blood sugar, rare reports of cognitive impairment, peripheral neuropathy.
• Timing: Muscle symptoms typically occur within weeks to months of therapy initiation or dose increase.
• Dose-dependent: Higher doses carry higher risk of muscle-related side effects.

• Major interactions:
• Cyclosporine: greatly increases rosuvastatin levels — avoid combination.
• Warfarin: may enhance anticoagulant effect; monitor INR closely.
• Gemfibrozil and other fibrates: increased risk of myopathy/rhabdomyolysis.
• Antacids: may reduce absorption if taken simultaneously; separate dosing by 2 hours.
• Enzyme involvement: Minimal CYP metabolism; primarily CYP2C9. Fewer CYP3A4 interactions compared to other statins.
• Food & alcohol: No major food interaction; avoid excessive alcohol to reduce liver damage risk.

• Updated guidelines emphasize moderate-to-high intensity statin therapy for primary and secondary prevention of cardiovascular disease, with rosuvastatin 20-40 mg considered high intensity.
• EMA and FDA warnings reinforce dose limitations and caution in Asian populations due to pharmacokinetic differences.
• Monitoring recommendations for muscle toxicity and liver enzymes remain unchanged but stressed in new statin use protocols.
• Recent data highlight rosuvastatin's potential pleiotropic effects beyond lipid lowering, including anti-inflammatory benefits.

• Store at controlled room temperature between 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container with desiccant.
• Do not freeze.
• No special reconstitution needed (oral tablets).