Atogal (Ingers (Czech Republic));Atorpic;Cardyl (Pfizer (Spain));Faboxim (Fabop (Argentina));Hipolixan (Pasteur (Chile));Lipitor (Pfizer, Elea (Argentina));Lipotropic (Drugtech (Chile));Lipovastatinklonal (Klonal (Argentina));Liprimar (Pfizer (Hungary, Ukraine), Goedecke (Russia));Lowden (Saval (Chile));Normalip (Quesada (Argentina));Sincol (Indeco (Argentina));Sortis (Pfizer (Austria, Czech Republic, Germany, Hungary, Poland, Portugal, Switzerland), Godecke (Germany), Parke, Davis (Germany));Sotis;Torvacard (Zentiva (Czech Republic, Hungary, Poland, Russia, Ukraine));Torvast (Pfizer (Italy));Totalip (Guidotti (Italy));Tozalip;Tulip (Lek (Czech Republic, Russia), Wermar (Mexico), Sandoz (Poland, Ukraine), Pharmacia (Spain));Vastina (Penn (Argentina));Xanator (Sieger (Greece));Xarator (Parke, Davis (Italy));Xavator;Zurinel (Prater (Chile));

Atorvastatin calcium;

Atorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.

• Pfizer inc

• Advanced Pharmaceutical Services Inc.
• Apotheca Inc.
• A-S Medication Solutions LLC
• Atlantic Biologicals Corporation
• Bryant Ranch Prepack
• Cardinal Health
• Direct Pharmaceuticals Inc.
• Dispensing Solutions
• Diversified Healthcare Services Inc.
• Goedecke GmbH
• Healthcare Pharmacy
• Heartland Repack Services LLC
• Kaiser Foundation Hospital
• Lake Erie Medical and Surgical Supply
• Murfreesboro Pharmaceutical Nursing Supply
• Nucare Pharmaceuticals Inc.
• Orifice Medical AB
• PCA LLC
• PD-Rx Pharmaceuticals Inc.
• Pfizer Inc.
• Pharmaceutical Utilization Management Program VA Inc.
• Physicians Total Care Inc.
• Prepackage Specialists
• Prepak Systems Inc.
• Resource Optimization and Innovation LLC
• Sandhills Packaging Inc.
• Southwood Pharmaceuticals
• Tya Pharmaceuticals
• US Pharmaceutical Group
• Vangard Labs Inc.
• Vitrum Ab
• Warner Lambert Company LLC

Synthesis Reference

Not Available

General Reference

Rouleau J: Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial. Am J Med. 2005 Dec;118 Suppl 12A:28-35. Pubmed Maggon K: Best-selling human medicines 2002-2004. Drug Discov Today. 2005 Jun 1;10(11):739-42. Pubmed

Type	small molecule

Classes

Not Available

Substructures

Not Available

hyperlipidemi 高血脂;

Indication	May be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels.
Pharmacodynamics	Atorvastatin, a selective, competitive HMG-CoA reductase inhibitor, is used to lower serum total and LDL cholesterol, apoB, and triglyceride levels while increasing HDL cholesterol. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, atorvastatin reduces the risk of cardiovascular morbidity and mortality. Atorvastatin has a unique structure, long half-life, and hepatic selectivity, explaining its greater LDL-lowering potency compared to other HMG-CoA reductase inhibitors.
Mechanism of action	Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
Absorption	Atorvastatin is rapidly absorbed after oral administration with maximum plasma concentrations achieved in 1 to 2 hours. The absolute bioavailability of atorvastatin (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic bioavailability is due to presystemic clearance by gastrointestinal mucosa and first-pass metabolism in the liver.
Volume of distribution	381 L
Protein binding	>98% bound to plasma proteins
Metabolism	Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. CYP3A4 is also involved in the metabolism of atorvastatin. Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us. Substrate Enzymes Product Atorvastatin Cytochrome P450 3A4 Cytochrome P450 3A5 Cytochrome P450 2C8 <i>para</i>-hydroxyatorvastatin Details Atorvastatin Cytochrome P450 3A4 Cytochrome P450 3A5 <i>ortho</i>-hydroxyatorvastatin Details
Route of elimination	Eliminated primarily in bile after hepatic and/or extrahepatic metabolism. Does not appear to undergo significant enterohepatic recirculation. Less than 2% of the orally administered dose is recovered in urine.
Half life	14 hours, but half-life of HMG-CoA inhibitor activity is 20-30 hours due to longer-lived active metabolites
Clearance	Not Available
Toxicity	Generally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered.
Affected organisms	Humans and other mammals
Pathways	Pathway Name SMPDB ID Atorvastatin Pathway SMP00131

Properties
State	solid
Experimental Properties	Property Value Source melting point 159.2-160.7 °C Not Available water solubility Sodium salt soluble in water, 20.4 ug/mL (pH 2.1), 1.23 mg/mL (pH 6.0) Not Available logP 5.7 Not Available
Predicted Properties	Property Value Source water solubility 6.30e-04 g/l ALOGPS logP 4.24 ALOGPS logP 5.39 ChemAxon logS -6 ALOGPS pKa (strongest acidic) 4.33 ChemAxon pKa (strongest basic) -2.7 ChemAxon physiological charge -1 ChemAxon hydrogen acceptor count 5 ChemAxon hydrogen donor count 4 ChemAxon polar surface area 111.79 ChemAxon rotatable bond count 12 ChemAxon refractivity 158.2 ChemAxon polarizability 59.25 ChemAxon

Drug	Interaction
Alvimopan	Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Amprenavir	Amprenavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
Atazanavir	Atazanavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
Bezafibrate	Increased risk of myopathy/rhabdomyolysis
Boceprevir	Boceprevir increases the exposure of atorvastatin. Concomitant therapy should be closely monitored.
Bosentan	Bosentan may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if bosentan is initiated, discontinued or dose changed.
Carbamazepine	Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of atorvastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if carbamazepine is initiated, discontinued or dose changed.
Clarithromycin	The macrolide, clarithromycin, may increase the toxicity of the statin, atorvastatin.
Colchicine	Increased risk of rhadbomyolysis with this combination.
Cyclosporine	Possible myopathy and rhabdomyolysis
Delavirdine	Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if delavirdine is initiated, discontinued or dose changed.
Diltiazem	Diltiazem may increase the serum concentration of atorvastatin. Atorvastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Dronedarone	Dronedarone is a CYP2D6 inhibitor thus increasing serum concentrations of atorvastatin. Lower doses of atorvastatin or consider rosuvastatin as cholesterol lowering therapy as there is no significant interaction between rosuvastatin and dronedarone.
Efavirenz	Efavirenz may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if efavirenz is initiated, discontinued or dose changed.
Eltrombopag	Eltrombopag increases levels of Atorvastatin via metabolism decrease.
Erythromycin	The macrolide, erythromycin, may increase the toxicity of the statin, atorvastatin.
Etravirine	Atorvastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of atorvastatin therapy.
Fenofibrate	Increased risk of myopathy/rhabdomyolysis
Fluconazole	Increased risk of myopathy/rhabdomyolysis
Fosamprenavir	Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if fosamprenavir is initiated, discontinued or dose changed.
Fusidic Acid	Increased risk of myopathy/rhabdomyolysis
Gemfibrozil	Increased risk of myopathy/rhabdomyolysis
Imatinib	Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if imatinib is initiated, discontinued or dose changed.
Indinavir	Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
Itraconazole	Increased risk of myopathy/rhabdomyolysis
Josamycin	The macrolide, josamycin, may increase the toxicity of the statin, atorvastatin.
Ketoconazole	Increased risk of myopathy/rhabdomyolysis
Lomitapide	Atorvastatin, and other weak CYP3A4 inhibitors (such as amiodarone, amlodipine, alprazolam, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginko, goldenseal, isoniazide, lapatinib, nilotinib, oral contraceptives, pazopanib, ranitidine, ranolazine, tipranavir/ritonavir, ticagrelor, zileuton) increase lomitapide levels by 2-fold. Thus lomipatide should be dosed at a maximum of 30mg daily when used concomitantly with weak inhibitors of CYP3A4.
Nefazodone	Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nefazodone is initiated, discontinued or dose changed.
Nelfinavir	Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nelfinavir is initiated, discontinued or dose changed.
Nevirapine	Nevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nevirapine is initiated, discontinued or dose changed.
Quinupristin	This combination presents an increased risk of toxicity
Rifabutin	Rifabutin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifabutin is initiated, discontinued or dose changed.
Rifampin	Rifampin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifampin is initiated, discontinued or dose changed.
Ritonavir	Ritonavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if ritonavir is initiated, discontinued or dose changed.
Saquinavir	Saquinavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if saquinavir is initiated, discontinued or dose changed.
Telaprevir	Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telithromycin	The macrolide antibiotic, telithromycin, may increase the serum concentration of atorvastatin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if telithromycin is initiated, discontinued or dose changed.
Tipranavir	Tipranavir, co-administered with Ritonavir, increases the adverse/toxic effects of Atorvastatin. Concomitant therapy should be avoided.
Topotecan	The p-glycoprotein inhibitor, Atorvastatin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Verapamil	Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Atorvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Atorvastatin if Verapamil is initiated, discontinued or dose changed.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if voriconazole is initiated, discontinued or dose changed.

• Avoid alcohol.
• Avoid drastic changes in dietary habit.
• Avoid taking grapefruit or grapefruit juice throughout treatment. Grapefruit can significantly increase serum levels of this product.
• Food may decrease maximum plasma levels and area under the curve, but this is clinically inconsequential according to the manufacturer.
• Take with low fat meal.