rosuvastatin

HMG-CoA reductase inhibitor· Brands: Crestor, Rosuvas, RosucorPO

Mechanism of action

Rosuvastatin is a competitive inhibitor of HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis. This reduces hepatic cholesterol synthesis, leading to upregulation of LDL receptors and increased clearance of LDL from the blood, lowering LDL cholesterol and triglycerides, and slightly increasing HDL cholesterol.

Pharmacokinetics

Rosuvastatin is administered orally. It has a bioavailability of about 20%, with peak plasma concentrations in 3-5 hours. It is not extensively metabolised; only about 10% is metabolised, and it is excreted primarily in faeces, with some renal excretion. Its half-life is approximately 19 hours, allowing once-daily dosing. It is a substrate for OATP1B1 and BCRP transporters; it is not metabolised by CYP3A4, so drug interactions differ from other statins.

Indications & dosing

Primary hypercholesterolaemia (including heterozygous familial hypercholesterolaemia)

Initial dose usually 5-10 mg. Adjust based on LDL-C response.

adult · PO: 5–20 mg once daily · Initial dose usually 5-10 mg. Adjust based on LDL-C response.

Homozygous familial hypercholesterolaemia

Start at 20 mg, may increase to 40 mg if needed.

adult · PO: 20–40 mg once daily · Start at 20 mg, may increase to 40 mg if needed.

Prevention of cardiovascular events

For patients at high cardiovascular risk, consider 10-20 mg.

adult · PO: 5–10 mg once daily · For patients at high cardiovascular risk, consider 10-20 mg.

Heterozygous familial hypercholesterolaemia in children and adolescents

For children 6-17 years; use lowest dose titrated to response.

pediatric · PO: 5–20 mg once daily · For children 6-17 years; use lowest dose titrated to response.

Contraindications & precautions

Pregnancy · Statins are contraindicated during pregnancy; may cause fetal harm.
Breastfeeding · Statins are contraindicated during breastfeeding; may be present in milk.
Active liver disease · Including unexplained persistent transaminase elevation.
Hypersensitivity to rosuvastatin or any excipient · Rare but serious allergic reactions can occur.
Severe renal impairment · Use with caution; dose adjustment required. Contraindicated in some regions for CrCl <30 mL/min.
Measure baseline serum creatinine and estimate renal function; adjust starting dose in patients with renal impairment.
Monitor liver function tests before starting treatment and periodically; discontinue if transaminases persist above 3 times the upper limit of normal.
Use caution in patients with predisposing factors for myopathy, such as hypothyroidism, alcohol abuse, or a history of myopathy with another statin.
Be aware of drug interactions that increase rosuvastatin concentrations or myopathy risk, including ciclosporin, gemfibrozil, certain antiretrovirals, azole antifungals, and macrolides.
Start with a lower dose in patients of Asian origin due to increased systemic exposure to rosuvastatin.
Caution in patients with risk factors for type 2 diabetes; monitor blood glucose as statin therapy may increase the risk of new-onset diabetes.

Adverse effects

Myalgia
Headache
Nausea
Abdominal pain
Rhabdomyolysisserious
Myopathyserious
Liver enzyme elevationserious
New-onset diabetesserious
Immune-mediated necrotizing myopathyserious

Interactions

cyclosporinemajorAvoid concomitant use where possible. If co-administration is essential, use the lowest effective rosuvastatin dose (not exceeding 5 mg daily) and monitor the patient for muscle symptoms and for creatine kinase elevations at baseline and periodically thereafter. Reassess renal function and consider an alternative statin with less interaction potential.

Renal & hepatic adjustment

eGFR 30–59: No dose adjustment required for mild renal impairment (eGFR 60+); for moderate renal impairment (eGFR 30-59), the maximum dose should not exceed 10 mg. Initiate at 5 mg if severe risk of myopathy, and monitor renal function.
eGFR 0–29: Contraindicated in severe renal impairment (eGFR <30 ml/min/1.73m2). Consider alternative statin. (avoid)
Hepatic impairment (mild): No dose adjustment required in patients with mild hepatic impairment, but use with caution. Monitor liver function.
Hepatic impairment (moderate): No dose adjustment required, but use with caution in moderate hepatic impairment. Monitor liver function.
Hepatic impairment (severe): Contraindicated in active liver disease or unexplained persistent elevation of transaminases. Avoid in severe hepatic impairment. (avoid)

Monitoring, pregnancy & toxicity

Serum lipids (total cholesterol, LDL-C, HDL-C, triglycerides) · At baseline, 4-12 weeks after initiation or dose adjustment, then every 6-12 months
Liver function tests (ALT, AST) · At baseline, then 3-12 months, and if symptoms of hepatotoxicity occur
Creatine kinase (CK) · At baseline if patient has risk of myopathy, and if muscle symptoms develop
Renal function (serum creatinine, eGFR) · At baseline, and periodically in patients with renal impairment
Pregnancy: Contraindicated in pregnancy. Should be discontinued if pregnancy is planned or occurs. Inform patients of the risk.
Toxicity: Muscle pain, tenderness, weakness, or elevated creatine kinase (CK) levels. · Discontinue rosuvastatin. Check CK levels. Monitor for rhabdomyolysis.
Toxicity: Severe muscle damage, markedly elevated CK, myoglobinuria, and acute kidney injury. · Discontinue immediately. Admit to hospital. Aggressive hydration, monitor renal function and electrolytes.
Toxicity: Elevated serum transaminases (ALT/AST), hepatitis, jaundice. · Discontinue rosuvastatin and evaluate liver function. Consider alternative therapy.

Clinical notes

Rosuvastatin is used for hypercholesterolaemia, mixed dyslipidaemia, and prevention of cardiovascular events. It is more potent than simvastatin and atorvastatin on a milligram basis. Usual starting dose is 5-10 mg once daily, with dose adjustments based on lipid response. It is contraindicated in pregnancy, breastfeeding, and active liver disease. Caution in renal impairment, as the dose should be limited in moderate to severe renal impairment. Monitor liver function and creatine kinase if muscle symptoms occur. Interactions include ciclosporin, warfarin, and certain antacids.

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BNF; local formulary