Rosuvastatin

HMG-CoA reductase inhibitors (statins)

ATC code: C10AA07 (Rosuvastatin)

Mechanism of action

Competitive HMG-CoA reductase inhibitor, like atorvastatin. Key differences: more potent LDL lowering per milligram – reduces LDL by 45-55% at the maximum dose. Hydrophilic, with minimal CYP3A4 metabolism – resulting in fewer drug interactions with macrolides, azoles, and grapefruit.

Indications

Dyslipidemia, primary CV prevention

First line

Prescribed according to cardiovascular risk stratification, same as atorvastatin. Rosuvastatin's advantage is greater LDL reduction at lower doses: 5-10 mg of rosuvastatin is equivalent to 20-40 mg of atorvastatin. Convenient when potent lipid lowering is needed at a minimal dose.

Established ASCVD, secondary prevention

First line

High-intensity statin (rosuvastatin 20-40 mg daily) for secondary prevention in established ASCVD. ESC/EAS 2019 target: LDL reduction over 50% from baseline and below 1.4 mmol/L. The JUPITER trial showed a 44% reduction in cardiovascular events in patients with elevated CRP. Interchangeable with atorvastatin in the high-intensity regimen.

Familial hypercholesterolemia

First line

Familial hypercholesterolemia requires high-intensity statins. Rosuvastatin 20-40 mg provides the greatest LDL reduction among oral statins. If insufficient, ezetimibe is added, followed by PCSK9 inhibitors.

Practical notes

Timing and administration

May be taken at any time of day, with or without food. Half-life is about 19 hours, so evening dosing is not mandatory. The key is consistent daily timing.

Special situations

The key practical difference from atorvastatin is that rosuvastatin has minimal CYP3A4 interactions. Grapefruit, macrolides, and azole antifungals do not affect its levels. This simplifies regimens for patients on multiple drugs. Caution is needed with cyclosporine and gemfibrozil, which increase rosuvastatin levels via other mechanisms.

Safety

Contraindications

Active liver disease or unexplained persistent transaminase elevation
Pregnancy and planned pregnancy
Breastfeeding
Severe renal impairment (CrCl below 30 mL/min) for the 40 mg dose
Hypersensitivity to rosuvastatin or any component

Serious adverse effects

Rhabdomyolysis (rare, under 0.1%)
Immune-mediated necrotizing myopathy (very rare)
Proteinuria and hematuria at 40 mg dose (dose-dependent, usually transient)

Common adverse effects

Myalgia without CK elevation
Headache
Dyspepsia, nausea
Arthralgia
Transient transaminase elevation

PregnancyFDA X

FDA category X. Cholesterol is essential for fetal development. Statins are contraindicated in pregnancy. Discontinue 3 months before planned conception.

Breastfeeding

Contraindicated during breastfeeding.