Atorvastatin

Generic Name

Atorvastatin

Brand Names

Lipitor

Sortis

Torvast

Atoris

Ator

Lipvas

Tonact

Totalip

Various generics globally approved

Drug Class

HMG-CoA reductase inhibitor (statin)

Lipid-lowering agent

Belongs to the antilipemic agents class

Classified as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase

Mechanism of Action

Atorvastatin selectively and competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway in the liver

This results in a decrease in intrahepatic cholesterol levels

The reduction stimulates upregulation of hepatic LDL receptors, enhancing uptake and catabolism of circulating low-density lipoprotein cholesterol (LDL-C)

Ultimately leads to reduced serum LDL-C, total cholesterol, and apolipoprotein B

Also exerts modest effects on triglycerides and causes minor HDL elevation

Has pleiotropic effects: improves endothelial function, stabilizes atherosclerotic plaques, and reduces inflammation

Indications

Approved Indications

Hypercholesterolemia (primary and mixed dyslipidemia)

Familial hypercholesterolemia (homozygous and heterozygous)

Hypertriglyceridemia

Primary prevention of cardiovascular disease (in high-risk patients)

Secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD)

Post-myocardial infarction

Stroke prevention

Adjunct to diet in patients with type 2 diabetes and additional risk factors

Combined hyperlipidemia in patients with other metabolic disorders

Children ≥10 years old with familial hypercholesterolemia

Off-Label Uses

Prevention of preeclampsia in high-risk pregnancies (investigational)

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)

Polycystic ovary syndrome (PCOS)-related dyslipidemia

Chronic kidney disease for cardiovascular risk reduction

Autoimmune disease patients with high cardiovascular risk

Peripheral arterial disease management

Dosage and Administration

Adults

Initial dose: 10–20 mg once daily

Range: 10–80 mg once daily

Start at 40 mg in patients requiring >45% LDL-C reduction

Dosing is independent of meals

Taken preferably in the evening, but can be taken any time of day due to long half-life

Adjust dose at intervals of 2–4 weeks based on lipid profile

Pediatrics (Children ≥10 years)

Initial: 10 mg once daily

Maximum: 20 mg once daily in children

Maximum: 80 mg once daily in adolescents with familial hypercholesterolemia

Dose individualized based on lipid targets and tolerance

Geriatrics

No dosage adjustment required

Higher susceptibility to adverse effects—monitor closely

Hepatic Impairment

Contraindicated in active liver disease

Use with caution in history of hepatic dysfunction

Renal Impairment

No dosage adjustment required

Use with caution in severe impairment

Pharmacokinetics

Absorption: ~14% bioavailability

Peak plasma time: 1–2 hours

Protein binding: ≥98%

Metabolism: hepatic via CYP3A4 to active metabolites (ortho- and parahydroxyatorvastatin)

Half-life: ~14 hours (effective inhibitory activity >20–30 hours due to active metabolites)

Excretion: primarily via bile, <2% via urine

Contraindications

Active liver disease or persistent unexplained elevations in hepatic transaminases

Pregnancy

Lactation

Hypersensitivity to atorvastatin or any statin

Concomitant use with cyclosporine, in some cases depending on dose

Warnings and Precautions

May cause hepatic dysfunction—monitor liver enzymes before initiation and during therapy

Risk of myopathy and rhabdomyolysis—higher with high doses, advanced age, renal insufficiency, hypothyroidism, or drug interactions

Temporarily discontinue in patients with acute serious illness, trauma, surgery, or severe metabolic disturbance

Use with caution in heavy alcohol use

Monitor glucose levels—statins may increase HbA1c or fasting glucose

Risk of immune-mediated necrotizing myopathy (rare but serious)

Potential cognitive effects: memory loss, confusion (reversible)

Adverse Effects

Very Common

Headache

Diarrhea

Nasopharyngitis

Arthralgia

Pain in extremity

Dyspepsia

Increased liver enzymes (ALT/AST)

Common

Myalgia

Nausea

Insomnia

Back pain

Hyperglycemia

Flatulence

Urinary tract infections

Edema

Dizziness

Uncommon

Rash

Elevated creatine kinase (CK)

Fatigue

Depression

Paresthesia

Rare but Serious

Hepatitis

Rhabdomyolysis with acute renal failure secondary to myoglobinuria

Pancreatitis

Anaphylaxis

Interstitial lung disease

Immune-mediated necrotizing myopathy

Tendon rupture (postmarketing)

Pregnancy and Lactation

Pregnancy

Contraindicated

Category X (now defunct FDA system)—potential for fetal harm

Cholesterol is essential for fetal development

Discontinue at least 1–2 months before planned conception

Do not use in women trying to conceive

Lactation

Contraindicated

Excreted in animal milk—potential for serious adverse effects

Recommend discontinuing breastfeeding or using alternative lipid-lowering agents

Drug Interactions

CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir)

Increase atorvastatin plasma levels—risk of myopathy

Avoid or use with dose reduction and monitoring

Fibrates (especially gemfibrozil)

Increased risk of rhabdomyolysis

Avoid combination or monitor closely

Niacin (≥1g/day)

May increase risk of muscle-related adverse effects

Cyclosporine

Substantial increase in atorvastatin levels

Avoid or limit atorvastatin to 10 mg

Colchicine

May increase myopathy risk—use with caution

Digoxin

Atorvastatin may increase digoxin levels—monitor

Oral contraceptives (ethinyl estradiol/norethindrone)

Slight increase in hormone levels

Warfarin

May increase INR—monitor during initiation or discontinuation

Grapefruit juice

CYP3A4 inhibitor—limit to <1 liter/day

Monitoring Parameters

Baseline and periodic lipid profile (LDL, HDL, TG, Total-C)

Baseline liver function tests, then as clinically indicated

Creatine kinase (CK) if myopathy symptoms occur

HbA1c and glucose (in diabetics or at-risk patients)

Renal function in suspected rhabdomyolysis

Muscle symptoms (weakness, tenderness, pain)

Counseling Points

Take once daily, same time each day

Continue cholesterol-lowering diet and lifestyle modifications

Report unexplained muscle pain, tenderness, or weakness

Avoid grapefruit juice in large quantities

Do not use during pregnancy or breastfeeding

Routine lab monitoring is essential

Inform all prescribers you are on atorvastatin

May not feel any different on therapy—important for long-term cardiovascular benefit

Comparative Notes

Atorvastatin vs Simvastatin

Atorvastatin has a longer half-life, more potent LDL reduction

Less interaction with CYP3A4 inhibitors compared to simvastatin

Simvastatin is dosed at night; atorvastatin is flexible

Atorvastatin vs Rosuvastatin

Rosuvastatin is more potent per mg for LDL lowering

Atorvastatin more metabolized by liver (CYP3A4); rosuvastatin by CYP2C9

Both offer similar cardiovascular risk reduction

Atorvastatin vs Pravastatin

Pravastatin has fewer drug interactions, lower potency

Atorvastatin offers more LDL reduction and evidence for secondary prevention

Regulatory and Legal Status

Prescription-only

Included in WHO Model List of Essential Medicines

FDA approved since 1996 (Lipitor)

MHRA and EMA approved

Available globally in oral tablets: 10 mg, 20 mg, 40 mg, 80 mg

Included in numerous cardiovascular treatment guidelines (AHA/ACC, ESC, NICE)