Atorvastatin
Atorvastatin is a high-intensity statin used in adults for primary and secondary prevention of cardiovascular disease. It inhibits HMG-CoA reductase, reducing LDL cholesterol and lowering the risk of cardiovascular events.
- Chemical formula
- C33H35FN2O5
- CAS number
- 134523-00-5
- ATC code
- C10AA05
- Molecular weight
- 558.65 g/mol
- Drug class
- HMG-CoA reductase inhibitor (statin)
- Also known as
- CI-981, Atorvastatina
What is it?
Atorvastatin is a synthetic HMG-CoA reductase inhibitor approved in the United States in 1996. It is supplied as oral tablets at multiple strengths and is one of the most widely prescribed lipid-lowering medications. Atorvastatin is dispensed only on prescription and is part of the World Health Organization List of Essential Medicines. The molecule is classified as a high-intensity statin at higher doses, capable of reducing LDL cholesterol by approximately 50% or more.
Mechanism of action
Atorvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. Reduced intracellular cholesterol upregulates LDL receptors on the hepatocyte surface, increasing clearance of circulating LDL. The drug also has pleiotropic effects on endothelial function, inflammation and plaque stability. The clinical result is a reduction in LDL cholesterol of approximately 30% to 60% depending on dose, and a corresponding decrease in major cardiovascular events.
Pharmacokinetics
Atorvastatin is rapidly absorbed orally, with peak plasma concentrations reached after one to two hours. Absolute bioavailability is approximately 14%, due to extensive first-pass hepatic uptake and metabolism, mainly by CYP3A4. Plasma protein binding exceeds 98%. The terminal half-life of the parent compound is about 14 hours, with active metabolites contributing to a longer effective half-life. Excretion is mainly biliary. Strong CYP3A4 inhibitors and grapefruit juice substantially increase exposure.
Indications
Atorvastatin is approved in adults for the treatment of primary hypercholesterolaemia and mixed dyslipidaemia, for the prevention of cardiovascular events in patients at elevated risk and for the secondary prevention of cardiovascular events after acute coronary syndrome, stroke or revascularisation. It is also approved in adolescents from age 10 with familial hypercholesterolaemia under specialist supervision. According to international guidelines, the choice of dose depends on baseline risk and target LDL.
Safety profile
The most common adverse effects include myalgia, gastrointestinal symptoms and mild elevations of liver enzymes. Severe muscle injury, including rhabdomyolysis, is rare but can be life-threatening, particularly when atorvastatin is combined with strong CYP3A4 inhibitors, fibrates or in renal impairment. New-onset diabetes has been reported with statin therapy. According to the prescribing information, patients should report unexplained muscle pain, weakness or dark urine, and liver function should be checked before starting therapy.
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Frequently asked questions
How is atorvastatin different from rosuvastatin? ▾
Both are high-intensity statins, but they differ in pharmacokinetics. Rosuvastatin is more hydrophilic, has a longer half-life of about 19 hours and is excreted predominantly unchanged, while atorvastatin is more lipophilic and undergoes extensive CYP3A4 metabolism. At equivalent LDL reductions, dose ranges differ. The choice between them is made by the prescriber based on individual response, drug interactions, kidney function and ethnicity.
Should atorvastatin be taken in the morning or at night? ▾
Atorvastatin can be taken at any time of day with or without food, because its long effective half-life provides sustained inhibition of cholesterol synthesis throughout the 24-hour cycle. This contrasts with shorter-acting statins such as simvastatin, which are typically taken in the evening. According to the prescribing information, consistency is more important than timing — taking the dose at the same time each day improves adherence.
Is statin-related muscle pain serious? ▾
Most statin-related muscle pain is benign and reversible after discontinuation, but rare cases of severe rhabdomyolysis can be life-threatening. Risk factors include high doses, combination with strong CYP3A4 inhibitors or fibrates, advanced age, female sex, low body mass and renal impairment. According to the prescribing information, unexplained muscle pain, weakness or dark urine should be reported promptly to the prescriber for evaluation.
Why avoid grapefruit juice with atorvastatin? ▾
Grapefruit juice inhibits CYP3A4, the enzyme primarily responsible for the metabolism of atorvastatin. Regular consumption can substantially increase plasma concentrations and the risk of adverse effects, including myopathy. According to the prescribing information, large or regular intake of grapefruit juice should be avoided during atorvastatin therapy, and any planned change in diet should be discussed with the prescriber.
What are the main contraindications for atorvastatin? ▾
Atorvastatin is contraindicated in known hypersensitivity to the molecule, in active liver disease or unexplained persistent elevation of serum transaminases, and during pregnancy and breastfeeding. Caution is required in renal impairment, in concurrent use of strong CYP3A4 inhibitors and in patients at high risk of myopathy. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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