atorvastatin
HMG-CoA reductase inhibitors· Brands: Lipitor, Atorva, Torvast, AtorisPO
Mechanism of action
Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the enzyme that catalyses the conversion of HMG-CoA to mevalonate, a rate-limiting step in hepatic cholesterol synthesis. Inhibition reduces intracellular cholesterol, upregulating LDL receptors on hepatocytes, increasing LDL clearance from plasma, and lowering LDL cholesterol. It also reduces triglyceride production and modestly increases HDL cholesterol.
Pharmacokinetics
Atorvastatin is administered orally. It undergoes extensive first-pass metabolism in the liver and gut wall, with systemic bioavailability about 14% for the parent drug. It is metabolised by CYP3A4 to active ortho- and para-hydroxy metabolites, which contribute most of the HMG-CoA reductase inhibitory activity. Plasma protein binding is >98%. Elimination is mainly via biliary excretion, with a mean plasma elimination half-life of about 14 hours for the parent drug, but the inhibitory effect lasts longer due to active metabolites. No significant renal excretion.
Indications & dosing
Lipid lowering / CV prevention
- adult · PO: 10–80 mg OD
Contraindications & precautions
- Active liver disease or unexplained persistent elevation of serum transaminases · Includes chronic active hepatitis, cirrhosis, and other hepatic disorders.
- Pregnancy · Statins may cause fetal harm; discontinue therapy if pregnancy is suspected or confirmed.
- Breastfeeding · Contraindicated during lactation due to potential adverse effects on the infant.
- Known hypersensitivity to atorvastatin or any of its excipients · Rare; includes anaphylaxis, angioedema, and skin reactions.
- Use with caution in patients with a history of liver disease or regular alcohol consumption.
- Use with caution in patients with risk factors for myopathy, including renal impairment, hypothyroidism, or concurrent use of fibrates or CYP3A4 inhibitors.
- Advise patients to report unexplained muscle pain, tenderness, or weakness, as rhabdomyolysis may occur.
- Monitor liver function tests before starting treatment and periodically thereafter.
- Use with caution in patients at risk of developing diabetes; monitor blood glucose levels.
Adverse effects
- Myalgia; rare rhabdomyolysis (esp. with CYP3A4 inhibitors)serious
Interactions
- clarithromycinmajorAvoid co-prescribing atorvastatin with clarithromycin where alternatives exist. If concurrent use is necessary, use the lowest effective atorvastatin dose (e.g., 10 to 20 mg daily) and monitor for muscle symptoms and creatine kinase levels regularly. Consider temporary suspension of atorvastatin during clarithromycin therapy if possible.
- cyclosporinemajorAvoid co-prescription where possible. If concurrent use is unavoidable, use the lowest recommended atorvastatin dose (e.g., 10 mg daily) and monitor for muscle symptoms and creatine kinase levels. Advise the patient to report unexplained muscle pain or weakness.
- erythromycinmajorAvoid co-prescription when possible. If the combination is necessary, consider using a less interacting macrolide (e.g., azithromycin) or reduce the atorvastatin dose. Monitor patients for muscle symptoms and check creatine kinase if symptoms occur.
- diltiazemmajorAvoid co-prescription if possible. If used together, limit the atorvastatin dose (e.g., no more than 20 mg daily) and monitor patients for symptoms of myopathy. Consider alternative statins not reliant on CYP3A4, such as pravastatin or rosuvastatin. If monitoring, check creatine kinase (CK) at baseline and if symptoms occur.
- amiodaronemajorAvoid co-prescribing high-dose atorvastatin with amiodarone. If combination is necessary, use the lowest effective dose of atorvastatin (e.g., starting at 10 mg/day) and monitor for signs of myopathy. Counsel the patient to report unexplained muscle pain or weakness. Measure creatine kinase at baseline and if symptoms develop. Consider alternative lipid-lowering therapy (e.g., pravastatin or rosuvastatin, which are less dependent on CYP3A4) where possible.
- fluconazolemoderateMonitor for muscle pain, weakness, and signs of rhabdomyolysis. Consider limiting the atorvastatin dose or using an alternative antifungal. If coadministration is necessary, use the lowest effective atorvastatin dose and monitor creatine kinase.
Renal & hepatic adjustment
- Hepatic impairment (mild): No dose adjustment required; monitor liver function.
- Hepatic impairment (moderate): No dose adjustment required; monitor liver function.
- Hepatic impairment (severe): Contraindicated in active liver disease or unexplained persistent transaminase elevations. (avoid)
Monitoring, pregnancy & toxicity
- Lipid profile (total cholesterol, LDL, HDL, triglycerides) · Baseline, then at 4-8 weeks after initiation and periodically thereafter
- Liver function tests (ALT, AST) · Before initiation, then periodically; measure if symptoms of liver injury occur
- Creatine kinase (CK) · If muscle pain, weakness, or tenderness occurs
- Pregnancy: Contraindicated in pregnancy. Discontinue atorvastatin immediately if pregnancy occurs.
- Toxicity: Myopathy presenting as muscle pain, tenderness, or weakness · Discontinue drug; check CK; consider alternative lipid-lowering therapy.
- Toxicity: Rhabdomyolysis with elevated CK and renal failure · Stop drug; hospitalise; aggressive hydration and monitor renal function.
- Toxicity: Hepatotoxicity with elevated transaminases · Monitor liver function; if enzyme levels >3x ULN, discontinue therapy.
- Toxicity: Overdose · Symptomatic treatment; monitor vital signs; no specific antidote.
Clinical notes
Atorvastatin is used for hypercholesterolaemia, dyslipidaemia, and prevention of cardiovascular events. It is taken once daily at any time, with or without food. Common adverse effects include myalgia, raised liver enzymes, and gastrointestinal upset. It is contraindicated in active liver disease and pregnancy. Interactions: potent CYP3A4 inhibitors (e.g. clarithromycin, itraconazole) increase plasma levels and risk of myopathy. Monitor liver function tests and lipid profile. Muscle pain or weakness should be reported, and creatine kinase may be checked.
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BNF; local formulary