Rosuvastatin (Crestor®)

Rosuvastatin is the most potent statin available and can lower LDL cholesterol by up to 55%. It is marketed under the brand name Crestor® and as a generic (e.g., Rosuvastatin-ratiopharm®, Rosuvastatin HEXAL®).

Unlike simvastatin and atorvastatin, rosuvastatin is only minimally broken down by CYP enzymes, which results in significantly fewer interactions with other medications. It is a hydrophilic statin that is preferentially taken up by the liver.

The JUPITER trial demonstrated that rosuvastatin significantly reduces cardiovascular events even in patients with normal cholesterol but elevated CRP (an inflammatory marker).

Rosuvastatin inhibits cholesterol biosynthesis particularly strongly:

Mechanism of action:

• Most potent inhibition of HMG-CoA reductase of all available statins
• Hydrophilic: preferentially taken up into liver cells
• Low uptake into muscle cells (theoretically fewer muscle problems)
• Strong compensatory upregulation of LDL receptors

Lipid-lowering effect:

• LDL cholesterol: reduction by 40–55% (dose-dependent)
• Triglycerides: reduction by 15–25%
• HDL cholesterol: increase by 8–14%

Special features:

• Minimal CYP3A4 metabolism → few interactions
• Mainly excreted unchanged via the liver
• Not affected by grapefruit juice
• Can be taken at any time of day

Onset of action: Marked LDL reduction after 1–2 weeks. Maximum effect after 4 weeks.

Rosuvastatin is suitable for:

• Adults with primary hypercholesterolemia
• Patients with familial hypercholesterolemia (severely elevated LDL)
• Mixed dyslipidemia
• Primary and secondary prevention of cardiovascular events
• Patients with elevated hsCRP and cardiovascular risk

Especially recommended for:

• High LDL that needs to be lowered substantially (> 50%)
• Many concomitant medications (few interactions)
• When atorvastatin is not sufficiently effective
• Familial hypercholesterolemia

Not suitable:

• Pregnancy and breastfeeding
• Active liver disease
• Severe renal insufficiency (all doses)
• History of myopathy while taking statins

Starting dose:

• 5–10 mg once daily

Usual dosages:

• 5 mg: start of therapy, especially in Asian patients or those at increased risk of myopathy
• 10 mg: standard dose for most patients
• 20 mg: when a greater reduction is required
• 40 mg: maximum dose, only for severe hypercholesterolemia under close monitoring

Available strengths:

• 5 mg, 10 mg, 20 mg, 40 mg film-coated tablets

LDL reduction by dose:

• 5 mg: approx. 38%
• 10 mg: approx. 43%
• 20 mg: approx. 48%
• 40 mg: approx. 53–55%

Dose adjustment:

• Moderate renal insufficiency (creatinine clearance < 60 ml/min): start with 5 mg, 40 mg contraindicated
• Severe renal insufficiency (creatinine clearance < 30 ml/min): contraindicated
• Asian patients: start with 5 mg (increased exposure)

How to take:

• Once daily at any time of day
• Regardless of meals
• Swallow the film-coated tablet with water

Advantages:

• No fixed time (unlike simvastatin, which must be taken in the evening)
• No grapefruit problem (unlike simvastatin and atorvastatin)

Important notes:

• First lab check after 4–12 weeks
• Regular monitoring of liver values, lipid profile, and kidney function
• If you have muscle pain or dark urine: contact a doctor immediately
• Thyroid function should be checked before starting therapy

If you miss a dose: Take it at the next regular time. Do not take a double dose.

Rosuvastatin must not be taken in cases of:

• Active liver disease or unexplained elevation of transaminases
• Pregnancy and breastfeeding
• Severe renal insufficiency (creatinine clearance < 30 ml/min, at all doses)
• Myopathy
• Concomitant cyclosporine therapy (at all doses)
• Hypersensitivity to rosuvastatin

Caution in cases of:

• Hypothyroidism
• Personal or familial muscle disease
• Asian ancestry (increased plasma levels, 40 mg contraindicated)
• Renal insufficiency (dose adjustment, 40 mg contraindicated from moderate renal insufficiency onwards)
• High alcohol consumption
• Concomitant use of fibrates (40 mg contraindicated)

Pregnancy: Strictly contraindicated. Reliable contraception required.

Common (1–10%):

• Headache
• Dizziness
• Myalgia (muscle pain)
• Gastrointestinal complaints (constipation, nausea)
• Asthenia (weakness)
• Elevated liver enzymes
• Diabetes mellitus (slightly increased risk, dose-dependent)

Uncommon (0.1–1%):

• Skin rash, pruritus
• Elevated CK levels
• Abdominal pain
• Proteinuria (at high doses)

Rare:

• Myopathy, rhabdomyolysis
• Pancreatitis
• Hepatitis
• Peripheral neuropathy

Note: In controlled studies, the rate of myopathy with rosuvastatin is comparable to that of other statins. The hydrophilic profile theoretically protects against uptake into muscle cells.

Advantage of rosuvastatin: Minimal CYP3A4 metabolism → significantly fewer interactions than simvastatin or atorvastatin.

Contraindicated with:

• Cyclosporine (all doses)

Dose limitation with:

• Gemfibrozil: rosuvastatin max. 20 mg
• Lopinavir/ritonavir, atazanavir/ritonavir: max. 10 mg
• Regorafenib: start with 5 mg, lower maximum dose (rosuvastatin exposure increased about 3.8-fold)

Caution with:

• Anticoagulants (warfarin, phenprocoumon) – monitor INR
• Fibrates (risk of myopathy)
• Fusidic acid (systemic): interrupt rosuvastatin during fusidic acid treatment, resume no earlier than 7 days after the last dose of fusidic acid

No relevant interaction with:

• Grapefruit juice (only minor metabolism via CYP3A4)
• Amiodarone, verapamil, diltiazem (no dose limitation needed, unlike with simvastatin)