Atorvastatin
Atorvastatin is a lipid-modifying medicine in the HMG-CoA reductase inhibitor class. According to the US prescribing information, it is indicated as an adjunct to diet to reduce LDL cholesterol, and to reduce the risk of heart attack, stroke, revascularisation procedures and angina in adults with multiple risk factors for coronary heart disease, including adults with type 2 diabetes who have multiple risk factors for CHD. In adults who already have clinically evident coronary heart disease, it is indicated to reduce the risk of non-fatal and fatal heart attack, non-fatal and fatal stroke, revascularisation procedures, hospitalisation for congestive heart failure and angina.
Key points
- Atorvastatin’s own plasma half-life is about 14 hours, but its inhibitory activity against HMG-CoA reductase lasts 20 to 30 hours, because active metabolites keep working after the parent drug has cleared.
- It is a substrate of the efflux transporter BCRP, which may limit how much of the drug is absorbed from the gut and how it is cleared into bile.
- Commonly reported side effects include nasopharyngitis, headache and hyperglycaemia; hypoglycaemia, weight gain and anorexia are uncommon.
How it works
The Lipitor SmPC places atorvastatin in the lipid-modifying, HMG-CoA-reductase inhibitor group. Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of sterols including cholesterol. The liver normally packages its triglycerides and cholesterol into very low-density lipoprotein (VLDL) for release into the plasma, and low-density lipoprotein (LDL) is then formed from VLDL and cleared mainly through the LDL receptor. By inhibiting HMG-CoA reductase and cholesterol production in the liver, atorvastatin increases the number of LDL receptors on liver cells, enhancing the uptake and breakdown of LDL, and it also reduces LDL production and the number of circulating LDL particles.
Safety specific to atorvastatin
Atorvastatin may cause myopathy (muscle pain, tenderness or weakness with a raised creatine kinase level) and rhabdomyolysis. Like other HMG-CoA reductase inhibitors, it may, on rare occasions, affect the skeletal muscle and progress from myalgia or myositis to rhabdomyolysis. It should be prescribed with caution in anyone with factors that predispose to rhabdomyolysis. Increases in liver enzymes (serum transaminases) have also been reported with atorvastatin. Liver function tests are recommended before starting treatment and periodically afterwards, and atorvastatin should be used with caution by anyone who drinks substantial amounts of alcohol or who has a history of liver disease.
When to seek urgent care
Seek urgent medical care for unexplained muscle pain, tenderness or weakness, as these can be signs of myopathy or rhabdomyolysis. Also seek urgent care for signs of a serious hypersensitivity reaction; reports with atorvastatin have included anaphylaxis, angioedema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.