Atorvastatin

Atorvastatin is an HMG-CoA reductase inhibitor (statin) and a cholesterol-lowering medication. It effectively lowers LDL cholesterol (“bad cholesterol”) by 41–61% depending on the dose, thereby reducing the risk of heart attack and stroke.

Atorvastatin is also known under the brand name Sortis® (or Lipitor® internationally). Today it is available as a generic (e.g., Atorvastatin-ratiopharm®, Atorvastatin HEXAL®, Atorvastatin-1 A Pharma®).

It is one of the statins and is used in patients with high cardiovascular risk.

Atorvastatin inhibits cholesterol synthesis in the liver:

Mechanism of action:

• Inhibits the enzyme HMG-CoA reductase (the key enzyme of cholesterol biosynthesis)
• The liver produces less cholesterol
• To compensate, more LDL receptors are formed on the surface of the liver
• More LDL cholesterol is taken up from the blood and broken down

Lipid-lowering effect:

• LDL cholesterol: reduction of 41–61% (dose-dependent)
• Triglycerides: reduction of 15–30%
• HDL cholesterol: slight increase of 5–10%

Pleiotropic effects (beyond lipid lowering):

• Stabilization of atherosclerotic plaques
• Inhibition of inflammation in the vessel walls
• Improvement of endothelial function

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

Atorvastatin is suitable for:

• Adults with hypercholesterolemia (elevated cholesterol)
• Patients with mixed dyslipidemia
• Secondary prevention after a heart attack or stroke
• Primary prevention in cases of high cardiovascular risk
• Familial hypercholesterolemia

Particularly recommended for:

• High LDL cholesterol that needs to be lowered substantially (> 50% reduction)
• Type 2 diabetes mellitus with increased cardiovascular risk
• Coronary heart disease (CHD), for secondary prevention
• Patients who prefer a flexible time of intake (not tied to a specific time)

Not suitable:

• Pregnancy and breastfeeding
• Active liver disease or unexplained elevation of transaminases
• Concomitant treatment with glecaprevir/pibrentasvir (hepatitis C)

Starting dose:

• 10–20 mg once daily (depending on the risk profile)

Usual dosages:

• 10 mg: mild cholesterol elevation, primary prevention
• 20 mg: moderate reduction, standard for many patients
• 40 mg: stronger reduction, after a heart attack
• 80 mg: maximum, high-risk patients, after acute coronary syndrome

Available strengths:

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

LDL reduction by dose:

• 41 to 61% depending on the dose (dose-response study)

Dose adjustment:

• Renal impairment: no adjustment needed
• Mild hepatic impairment: caution, close monitoring

How to take:

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

Advantage: Atorvastatin does NOT have to be taken in the evening. It has a long half-life (14 hours, active metabolite up to 30 hours) and can therefore be taken at any time of day.

Important notes:

• Regular laboratory checks (liver function tests, lipid profile) – first check after 4–12 weeks
• If you miss a dose: take it later if less than 12 hours have passed
• Avoid grapefruit juice in large quantities (inhibits CYP3A4)
• Limit alcohol consumption (to protect the liver)
• Report muscle complaints to your doctor immediately

Atorvastatin must not be taken in cases of:

• Active liver disease or unexplained, persistent elevation of transaminases (> 3-fold)
• Pregnancy and breastfeeding
• Hypersensitivity to atorvastatin

Caution in cases of:

• History of liver disease
• High alcohol consumption
• Hypothyroidism (underactive thyroid – increased risk of myopathy)
• History of muscle disorders
• Renal impairment (increased risk of myopathy)
• Concomitant use of CYP3A4 inhibitors (itraconazole, clarithromycin)

Pregnancy: Statins are strictly contraindicated throughout pregnancy. Cholesterol is essential for fetal development. Women of childbearing age must use reliable contraception.

Common (1–10%):

• Nasopharyngitis (cold symptoms)
• Myalgia (muscle pain) – the most common reason for stopping treatment
• Joint pain
• Gastrointestinal complaints (nausea, diarrhea, constipation)
• Elevated liver enzymes
• Headache
• Elevated blood glucose levels (mildly diabetogenic)

Uncommon (0.1–1%):

• Sleep disturbances
• Dizziness
• Skin rash

Rare but serious:

• Myopathy (muscle damage with elevated CK)
• Rhabdomyolysis (severe muscle breakdown – emergency!)
• Liver failure (extremely rare)
• Interstitial lung disease

Muscle pain: Occurs in about 5–10% of patients, but is usually mild. If you have severe muscle pain with dark-colored urine, see a doctor immediately (suspected rhabdomyolysis).

Increased risk of myopathy with:

• Ciclosporin (avoid the combination or limit the atorvastatin dose to 10 mg)
• Clarithromycin, erythromycin, itraconazole, ketoconazole (CYP3A4 inhibitors)
• Gemfibrozil and other fibrates
• Fusidic acid (combination contraindicated during treatment)
• Colchicine

Other interactions:

• Grapefruit juice in large quantities (> 1 liter/day) – CYP3A4 inhibition
• Rifampicin – accelerated breakdown, reduced effect
• Warfarin – enhanced anticoagulant effect (monitor INR)
• Digoxin – slightly increased digoxin levels
• Oral contraceptives – slightly increased ethinylestradiol levels

Note: Atorvastatin is broken down via CYP3A4. All medications that inhibit this enzyme can increase atorvastatin levels and thereby raise the risk of side effects.