Atorvastatin

Definition

ChEBI: Atorvastatin is a dihydroxy monocarboxylic acid that is a member of the drug class known as statins, used primarily for lowering blood cholesterol and for preventing cardiovascular diseases. It has a role as an environmental contaminant and a xenobiotic. It is an aromatic amide, a member of monofluorobenzenes, a statin (synthetic), a dihydroxy monocarboxylic acid and a member of pyrroles. It is functionally related to a heptanoic acid. It is a conjugate acid of an atorvastatin(1-).

Clinical Use

Hyperlipidaemia and hypercholesterolaemia

Drug interactions

Potentially hazardous interactions with other drugs Anti-arrhythmics: concentration possibly increased by dronedarone. Antibacterials: azithromycin, erythromycin, clarithromycin or fusidic acid possibly increased risk of myopathy - avoid atorvastatin for at least 7 days after fusidic acid stopped; concentration increased by clarithromycin - do not exceed 20 mg of atorvastatin1 ; avoid with telithromycin; increased risk of myopathy with daptomycin; concentration possibly reduced by rifampicin.
Anticoagulants: may transiently reduce anticoagulant effect of warfarin.
Antifungals: increased risk of myopathy with itraconazole - do not exceed 40 mg of atorvastatin1 ;
increased risk of myopathy with fluconazole, ketoconazole, posaconazole, voriconazole and possibly other imidazoles and triazoles - avoid.
Antivirals: increased risk of myopathy with atazanavir, boceprevir (reduce atorvastatin dose), and possibly darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir or tipranavir (max dose of atorvastatin 10 mg); concentration reduced by efavirenz and possibly etravirine; avoid with dasabuvir, ombitasvir, paritaprevir and telaprevir; possible increased risk of myopathy with ledipasvir - reduce atorvastatin dose; concentration increased by simeprevir - consider reducing atorvastatin dose.
Calcium channel blockers: concentration increased by diltiazem - increased risk of myopathy; concentration of verapamil increased also possible increased risk of myopathy - consider reducing atorvastatin dose.
Ciclosporin: increased risk of myopathy - do not exceed 10 mg of atorvastatin.1 Cobicistat: reduce atorvastatin dose.
Colchicine: possible increased risk of myopathy.
Grapefruit juice: concentration possibly increased.
Lipid lowering agents: increased risk of myopathy
with fibrates, gemfibrozil (avoid) and nicotinic acid.

Metabolism

Atorvastatin undergoes extensive presystemic clearance in gastrointestinal mucosa and/or hepatic first-pass metabolism. Atorvastatin is metabolised by cytochrome P450 3A4 to ortho- and parahydroxylated derivatives and various beta-oxidation products. These products are further metabolised via glucuronidation. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. Atorvastatin is eliminated primarily in bile as active metabolites following hepatic and/or extrahepatic metabolism, but does not appear to undergo significant enterohepatic recirculation.