Simvastatin

Simvastatin is an HMG-CoA reductase inhibitor (statin). It became known through the 4S study (Scandinavian Simvastatin Survival Study), which was the first to demonstrate a reduction in overall mortality with statin therapy.

Simvastatin is available as a generic from numerous manufacturers (e.g., Simvastatin-ratiopharm®, SimvaHEXAL®, Simvastatin-1 A Pharma®). The original product was Zocor®.

It is taken as a prodrug and converted in the liver into the active metabolite simvastatin acid. Simvastatin should preferably be taken in the evening, because cholesterol synthesis is highest at night.

Simvastatin inhibits the body's own cholesterol production:

Mechanism of action:

• Prodrug: converted in the liver into active simvastatin acid (beta-hydroxy acid)
• Competitively inhibits HMG-CoA reductase
• Reduces cholesterol biosynthesis in the liver
• Compensatory upregulation of LDL receptors
• Increased uptake of LDL cholesterol from the blood

Lipid-lowering effect:

• LDL cholesterol: reduction of 25–40% (dose-dependent)
• Triglycerides: reduction of 10–20%
• HDL cholesterol: increase of 5–10%

Pleiotropic effects:

• Plaque stabilization
• Anti-inflammatory action
• Improvement of endothelial function
• Antithrombotic effect

Onset of action: Measurable LDL reduction after 2 weeks. Maximum effect after 4–6 weeks.

Simvastatin is suitable for:

• Adults with hypercholesterolemia
• Patients with coronary heart disease (secondary prevention)
• People with diabetes at increased cardiovascular risk
• Primary prevention in high-risk patients

Particularly suitable:

• When a moderate LDL reduction (25–40%) is sufficient
• For patients who have tolerated it well for many years

Not suitable:

• Pregnancy and breastfeeding
• Active liver disease
• Concomitant use of strong CYP3A4 inhibitors
• When an LDL reduction of > 40% is required (atorvastatin or rosuvastatin is a better choice)

Starting dose:

• 10–20 mg once daily in the evening

Usual doses:

• 10 mg: mild cholesterol elevation
• 20 mg: standard dose for most patients
• 40 mg: greater reduction required

Maximum dose:

• 80 mg: only for severe hypercholesterolemia and a high risk of cardiovascular complications, if the treatment goals have not been reached with lower doses and the expected benefit outweighs the potential risks (increased risk of myopathy).

Available strengths:

• 10 mg, 20 mg, 40 mg, 80 mg film-coated tablets

LDL reduction by dose:

• 10 mg: approx. 25–30%
• 20 mg: approx. 30–35%
• 40 mg: approx. 35–40%

Important: If an LDL reduction of > 40% is needed, consider switching to atorvastatin or rosuvastatin instead of simvastatin 80 mg.

How to take:

• Take once daily in the EVENING
• With or without food
• Swallow the film-coated tablet with water

Why in the evening? The body's own cholesterol synthesis is highest at night. Simvastatin has a short half-life (2–3 hours), so taking it in the evening is important for maximum effect.

Important notes:

• NO large amounts of grapefruit juice (interaction!)
• First lab check after 4–12 weeks
• Have liver function tests and lipid profile checked regularly
• If you have muscle pain, muscle cramps, or dark urine: inform your doctor immediately
• Alcohol in moderation

Simvastatin must not be taken in cases of:

• Active liver disease or unexplained elevation of transaminases
• Pregnancy and breastfeeding
• Hypersensitivity to simvastatin
• Concomitant use of: itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin, nefazodone, cobicistat, gemfibrozil, cyclosporine, danazol

Use with caution in:

• Hypothyroidism
• Renal insufficiency
• High alcohol consumption
• History of muscle disease
• Elderly patients (> 70 years)
• Asian descent (increased rate of myopathy)

Pregnancy: Strictly contraindicated. Reliable contraception required.

Common (1–10%):

• Headache
• Gastrointestinal complaints (nausea, flatulence, diarrhea, constipation)
• Myalgia (muscle pain)
• Elevated liver enzymes
• Upper respiratory tract infections

Uncommon (0.1–1%):

• Dizziness
• Sleep disturbances
• Skin rash
• Indigestion
• Elevated blood glucose levels

Rare but serious:

• Myopathy (CK elevated > 10-fold, especially with 80 mg)
• Rhabdomyolysis (severe muscle breakdown – emergency!)
• Hepatitis
• Pancreatitis

80 mg dose: The rate of myopathy is significantly higher at 80 mg than at lower doses. Therefore, the 80 mg dose is only recommended for severe hypercholesterolemia and a high risk of cardiovascular complications if the treatment goals have not been reached with lower doses and the expected benefit outweighs the potential risks.

Contraindicated (increased risk of rhabdomyolysis):

• Strong CYP3A4 inhibitors: itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors
• Gemfibrozil
• Cyclosporine
• Danazol

Dose limitation with:

• Amiodarone: simvastatin max. 20 mg
• Verapamil, diltiazem: simvastatin max. 20 mg
• Amlodipine: simvastatin max. 20 mg
• Lomitapide: simvastatin max. 40 mg

Other interactions:

• Grapefruit juice: CYP3A4 inhibition → increased levels
• Warfarin: enhanced anticoagulant effect
• Colchicine: increased risk of myopathy
• Fusidic acid: combination contraindicated

Important: Simvastatin has more interactions than atorvastatin or rosuvastatin because it is metabolized to a greater extent via CYP3A4.