Rosuvastatin

Rosuvastatin is a potent water soluble statin that lowers LDL cholesterol by 40% to 60% and triglycerides by 10% to 35%. It lowers heart attacks, strokes and death in people with cardiovascular disease and in selected high risk people without it. It is cleared mostly unchanged in faeces, so it has few drug interactions through CYP3A4. Exposure is about twice as high in people of Asian ancestry, and it builds up in kidney impairment. It is widely available in East Africa.

Classification. Statin; HMG CoA reductase inhibitor; high intensity at 20 to 40 mg.

Mechanism. Blocks the rate limiting step of hepatic cholesterol synthesis; the liver raises LDL receptors and clears more LDL from the blood. It also stabilises plaque and lowers inflammation.

Pharmacodynamics. LDL cholesterol falls within 1 week, with the full effect at 4 weeks. Each doubling of dose adds about 6% more LDL reduction.

Pharmacokinetics. Oral bioavailability about 20%. Half life about 19 hours. About 10% is metabolised (mainly CYP2C9); about 90% is excreted unchanged, mostly in faeces and about 10% in urine. Protein binding 90%.

Primary prevention of cardiovascular disease and hypercholesterolaemia, adult. Start 5 to 10 mg once daily; titrate every 4 weeks; usual maintenance 10 to 20 mg once daily.

Established cardiovascular disease and acute coronary syndrome, adult. 20 to 40 mg once daily; the maximum 40 mg is for patients with severe hypercholesterolaemia and high risk who have not reached the target on 20 mg, under specialist care.

Familial hypercholesterolaemia in children, specialist. Age 6 to 9 years: 5 to 10 mg once daily; age 10 to 17 years: 5 to 20 mg once daily.

Start 5 mg and keep to 20 mg or less. People of Asian ancestry, age over 70 years, hypothyroidism, personal or family history of muscle disorder, alcohol excess, or a risk of raised levels.

Kidney impairment. Creatinine clearance under 30 mL/min (not on dialysis): start 5 mg once daily and do not exceed 10 mg daily.

Interaction limits. Ciclosporin: maximum 5 mg daily. Gemfibrozil: maximum 10 mg daily. Ritonavir boosted lopinavir or atazanavir: maximum 10 mg daily.

Contraindications. Active liver disease or unexplained persistent rise in transaminases; pregnancy; breastfeeding; severe kidney impairment (creatinine clearance under 30 mL/min) at the 40 mg dose; concurrent ciclosporin at doses above 5 mg; hypersensitivity.

Warnings. Myopathy and rhabdomyolysis (higher with the 40 mg dose, older age, kidney impairment, hypothyroidism); proteinuria and haematuria (usually harmless at 40 mg; reduce the dose if persistent); raised liver enzymes; new onset diabetes (small rise); immune mediated necrotising myopathy (rare); interstitial lung disease (rare).

Adverse effects. Muscle aches, headache, nausea, constipation, abdominal pain, raised liver enzymes, proteinuria, raised blood glucose.

Interactions. Ciclosporin, gemfibrozil, ritonavir boosted protease inhibitors, fenofibrate, niacin: raised levels (use the dose limits given for ciclosporin, gemfibrozil and ritonavir boosted protease inhibitors). Antacids containing aluminium or magnesium: give rosuvastatin 2 hours before. Warfarin: raised INR; check the INR when starting or changing the dose. Erythromycin: slightly lower levels. Oral contraceptives: small rise in oestrogen and norethisterone.

Special groups.

• Pregnancy: stop when pregnancy is planned or confirmed; avoid.

• Breastfeeding: avoid.

• Patients of African ancestry: no dose change.

• Patients of Asian ancestry: start 5 mg; avoid the 40 mg dose.

• Older adults: start low in frailty.

• Kidney impairment: creatinine clearance under 30 mL/min: start 5 mg, maximum 10 mg.

• Liver impairment: contraindicated in active disease.

Formulations. Tablets 5, 10, 20, 40 mg.

Administration. Oral once daily at any time of day, with or without food. Swallow whole.

Baseline. Lipid profile, alanine aminotransferase, creatinine, creatine kinase if muscle symptoms or risk factors, thyroid function if suspected hypothyroidism, glucose or HbA1c, pregnancy status, ancestry.

Monitoring. Lipid profile 4 to 12 weeks after starting or changing the dose, then every 6 to 12 months. Alanine aminotransferase at baseline and as needed. Creatine kinase only if muscle symptoms occur. Urine dipstick in people on 40 mg. Creatinine yearly.

Stopping. Stop for creatine kinase above 10 times the upper limit of normal, rhabdomyolysis, persistent transaminase rise above 3 times the upper limit of normal, or pregnancy. Restart at a lower dose after muscle symptoms settle.

Common prescribing errors. Using 40 mg in Asian ancestry or kidney impairment; starting at 20 mg in older or frail patients; combining with gemfibrozil without a dose cap; giving with ciclosporin above 5 mg; omitting a thyroid check in unexplained muscle pain.