Atorvastatin !

A potent statin: it blocks the liver's cholesterol-making enzyme, lowers LDL cholesterol and reduces heart attacks and strokes.

Updated 2026-11-01

Class: Statins
Enzyme: HMG-CoA reductase
ATC code: C10AA05
WHO Model List of Essential Medicines

HMG-CoA reductaseAtorvastatin

Target in 3D: HMG-CoA reductase. PDB structure 1HWK (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Atorvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, by occupying its HMG-CoA binding pocket. Less cholesterol inside liver cells activates SREBP-2, which raises the number of LDL receptors on the cell surface, so more LDL is removed from the blood. Its active metabolites carry most of the inhibition, so the effect outlasts the parent drug.

Occupies the HMG-CoA pocket of HMG-CoA reductase
Mevalonate and liver cholesterol synthesis fall
SREBP-2 adds LDL receptors to liver cells
Blood LDL falls: fewer heart attacks and strokes

Pharmacokinetics

Absorption: Oral, but extensive first-pass metabolism leaves an absolute bioavailability of about 14%.
Distribution: At least 98% bound to plasma proteins.
Metabolism: By CYP3A4 into active metabolites, which carry about 70% of the circulating inhibitory activity.
Elimination: Mainly in bile.
Half-life: About 14 hours; the inhibitory activity on HMG-CoA reductase lasts 20 to 30 hours.
Onset and duration: The LDL response can be checked from about four weeks after starting.

Indications

High LDL cholesterol and primary prevention in people at high cardiovascular risk Atherosclerosis and dyslipidaemia →
After a myocardial infarction or acute coronary syndrome (high-intensity secondary prevention) Myocardial Infarction (Heart Attack) →
After an atherosclerotic ischemic stroke or TIA Ischaemic stroke →

Adverse effects

Common

Muscle aches (myalgia)
Raised liver transaminases
Digestive upset: diarrhea, dyspepsia
Rises in HbA1c and fasting glucose

Contraindications

Acute liver failure or decompensated cirrhosis
Hypersensitivity to atorvastatin or an excipient
Pregnancy (it is stopped when pregnancy is recognized) and breastfeeding

Key interactions

Clarithromycin, itraconazole and several HIV protease inhibitors: Raise atorvastatin levels and the risk of myopathy; doses are limited or the combination is avoided.
Cyclosporine: Raises atorvastatin levels; the combination is not recommended.
Gemfibrozil: More myopathy; the combination is not recommended. With other fibrates the benefit is weighed against the muscle risk.
Large amounts of grapefruit juice: Raise levels; very large daily quantities are avoided.

What is monitored

Lipid panel before starting and from about four weeks after
Liver enzymes at baseline and if symptoms appear
Creatine kinase if there are muscle symptoms

Test yourself

Think of the answer, then tap the question to see it.

Why does atorvastatin's effect last longer than its plasma half-life suggests?

About 70% of the circulating inhibitory activity comes from active metabolites; atorvastatin's half-life is about 14 hours, but its inhibition of HMG-CoA reductase lasts 20 to 30 hours.

A patient on atorvastatin is prescribed clarithromycin. What is the concern?

Clarithromycin strongly inhibits CYP3A4, raising atorvastatin levels and the risk of myopathy; the atorvastatin dose is limited.

Which part of HMG-CoA reductase does atorvastatin occupy in crystal structures?

The HMG-CoA binding pocket of the catalytic domain: its dihydroxy acid chain mimics the HMG part, and its bulky ring system fills a nearby hydrophobic groove.

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Simvastatin

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Atorvastatin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - ATORVASTATIN CALCIUM- atorvastatin calcium tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH ATORVASTATIN (RCSB Protein Data Bank, 2001); eEML - Electronic Essential Medicines List (World Health Organization, 2025).

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Representative model, for educational purposes only.