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AtorvastatinSystematic (IUPAC) name(3R,5R)-7--3,5-dihydroxyheptanoic acidIdentifiersCAS number134523-00-5ATC codeC10AA05PubChem60823DrugBankAPRD00055ChemSpider54809Chemical dataFormulaC33H35FN2O5 Mol. mass558.64SMILESeMolecules & PubChemPharmacokinetic dataBioavailability12%MetabolismLiverHalf life14 hoursExcretionBileTherapeutic considerationsPregnancy cat.D(AU) X(US)Legal statusPrescription Only (S4)(AU) POM(UK) ℞-only(US)RoutesoralAtorvastatin (INN) (pronounced /əˌtɔrvəˈstætən/) (Lipitor, Pfizer), is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms.Atorvastatin inhibits HMG-CoA reductase, the rate-determining enzyme located in hepatic tissue that produces mevalonate, a small molecule used in the synthesis of cholesterol and other mevalonate derivatives. This lowers the amount of cholesterol produced which in turn lowers the total amount of LDL cholesterol.Atorvastatin was first synthesized in 1985 by Bruce Roth while working at Parke-Davis Warner-Lambert Company (now Pfizer).With 2006 sales of US$12.9 billion, Lipitor is the largest selling drug in the world.Lipitor is not the only statin; there are several other statins on the market.// PharmacologyMain article: StatinAs with other statins, atorvastatin is a competitive inhibitor of HMG-CoA reductase. Unlike most others, however, it is a completely synthetic compound. HMG-CoA reductase catalyzes the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, which is the rate-limiting step in hepatic cholesterol biosynthesis. Inhibition of the enzyme decreases de novo cholesterol synthesis, increasing expression of low-density lipoprotein receptors (LDL receptors) on hepatocytes. This increases LDL uptake by the hepatocytes, decreasing the amount of LDL-cholesterol in the blood. Like other statins, atorvastatin also reduces blood levels of triglycerides and slightly increases levels of HDL-cholesterol.In clinical trials, adding ezetimibe (Zetia) to Lipitor lowered cholesterol more effectively than Vytorin (ezetimibe + simvastatin). PharmacokineticsAtorvastatin has rapid oral absorption with an approximate time to maximum plasma concentration (Tmax) of 1-2 hours. The absolute bioavailability of atorvastatin is approximately 14%, however, the systemic availability for HMG-CoA reductase activity is approximately 30%. Atorvastatin undergoes high intestinal clearance and first-pass metabolism, which is the main cause for the low systemic availability. Food has shown to reduce the rate and extent of atorvastatin absorption. Administration of atorvastatin with food produces a 25% reduction in Cmax (rate of absorption) and a 9% reduction in AUC (extent of absorption). However, food does not affect the plasma LDL-C lowering efficacy of atorvastatin. Evening atorvastatin dose administration is known to reduce the Cmax (rate of absorption) and AUC (extent of absorption) by 30% each. However, time of administration does not affect the plasma LDL-C lowering efficacy of atorvastatin.atorvastatin is highly protein bound (≥98%) with a blood/plasma concentration ratio of 0.25 indicating a low red blood cell distribution.The primary proposed mechanism of atorvastatin metabolism is through cytochrome P450 3A4 hydroxylation to form active ortho- and parahydroxylated metabolites, as well as various beta-oxidation metabolites. The ortho- and parahydroxylated metabolites are responsible for 70% of systemic HMG-CoA reductase activity. The ortho-hydroxy metabolite undergoes further metabolism via glucuronidation. As a substrate for the CYP3A4 isozyme it has shown susceptibility to inhibitors and inducers of CYP 3A4 to produce increased or decreased plasma concentrations, respectively. This interaction was tested in vitro with concurrent administration of erythromycin, a known CYP 3A4 isozyme inhibitor, which resulted in increased plasma concentrations of atorvastatin. Atorvastatin is also an inhibitor of cytochrome 3A4.It is primarily eliminated via hepatic biliary excretion with less than 2% of atorvastatin recovered in the urine. Bile elimination follows hepatic and/or extra-hepatic metabolism. There does not appear to be any entero-hepatic recirculation. Atorvastatin has an approximate elimination half-life of 14 hours. Noteworthy, the HMG-CoA reductase inhibitory activity appears to have a half-life of 20-30 hours, which is thought to be due to the active metabolites. Atorvastatin is also a substrate of the intestinal P-glycoprotein efflux transporter, which pumps the drug back into the intestinal lumen during drug absorption.In Hepatic insufficiency, Plasma drug concentrations are significantly affected by concurrent liver disease. Patients with A stage liver disease show a 4-fold increase in both Cmax and AUC. Patients with B stage liver disease show an 16-fold increase in Cmax and an 11-fold increase in AUC.In Geriatric patients (>65 years old) show altered pharmacokinetics of atorvastatin compared to young adults. The mean AUC and Cmax values are higher (40% and 30%, respectively) for geriatric patients. Additionally, healthy elderly patients show a greater pharmacodynamic response to atorvastatin at any dose, therefore, this population may have lower effective doses. Clinical use FDA Approved IndicationsHypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb) to reduce total cholesterol, LDL-C, apo-B, Triglycerides levels, and CRP as well as increase HDL levels.Heterozygous familial hypercholesterolemia in pediatric patientsHomozygous familial hypercholesterolemiaHypertriglyceridemia (Fredrickson Type IV)Primary dysbetalipoproteinemia (Fredrickson Type III)It has also been used in the treatment of combined hyperlipidemia.Prophylaxis for myocardial infarction, stroke, unstable angina, and revascularization.*prophylaxis in patients with multiple risk factors without evident CHD.Myocardial infarction and stroke prophylaxis in patients with type II diabetes.Concomitant Therapy Considerations ContraindicationsActive liver disease: cholestasis, hepatic encephalopathy, hepatitis, and jaundice.Unexplained elevations in AST or ALT levelsPregnancy.Breast-feeding.Precaution must be taken when treating with atorvastatin, because rarely it may lead to rhabdomyolysis , it may be very serious leading to acute renal failure due to myoglobinuria. If rhabdomyolysis is suspected or diagnosed, atorvastatin therapy should be discontinued immediately.. Also Atorvastatin should be discontinued if a patient has markedly elevated CPK levels or if a myopathy is suspected or diagnosed. The likelihood of developing a myopathy is increased by the co-administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, and azole antifungalsAtorvastatin is absolutely contraindicated in pregnancy, it is likely to cause harm to fetal development because of the importance of cholesterol and various products in the cholesterol biosynthesis pathway for fetal development, including steroid synthesis and cell membrane production. It is not recommended that nursing mothers take atorvastatin due to the possibility of adverse reactions in nursing infants, since experiments with rats indicate that atorvastatin is likely to be secreted into human milk. Drug and Food InteractionsInteractions with clofibrate, fenofibrate, gemfibrozil, which are fibrates used in accessory therapy in many forms of hypercholesterolemia, usually in combination with statins , increase the risk of risk of myopathy and rhabdomyolysis.Co-administration of Atrovastatin with One of CYP3A4 inhibitors like itraconazole, telithromycin, and voriconazole, may increase serum concentrations of atorvastatin, which may lead to adverse reactions. This is less likely to happen with other CYP3A4 inhibitors like diltiazem, erythromycin, fluconazole, ketoconazole, clarithromycin, cyclosporine, protease inhibitors, verapamil. And only rearly with other CYP3A4 inhibitors like amiodarone, and aprepitant.often bosentan, fosphenytoin, and phenytoin which are CYP3A4 inducers can decrease the plasma concentrations of atorvastatin.But only rarely barbiturates, carbamazepine, efavirenz, nevirapine, oxcarbazepine, rifampin, and rifamycin, wich are CYP3A4 inducers can decrease the plasma concentrations of atorvastatin. Oral contraceptives increased AUC values for norethindrone and ethinyl estradiol, these increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin. Antacids can rarely decrease the plasma concentrations of atorvastatin but do not affect the LDL-C lowering efficacy.Niacin also is proved to increase the risk of myopathy or rhabdomyolysisStatins may also alter the concentrations of other drugs, such as warfarin or digoxin, leading to alterations in effect or a requirement for clinical monitoring.Vitamin D supplementation lowers atorvastatin and active metabolite concentrations yet has synergistic effects on cholesterol concentrations.Grapefruit juice components are known inhibitors of intestinal CYP3A4.Co-administration of grapefruit juice with atorvastatin may cause an increase in Cmax and AUC, which can lead to adverse reactions or overdose toxicity Available formsAtorvastatin calcium tablets are currently marketed by Pfizer under the trade name Lipitor, in tablets (10, 20, 40 or 80 mg) for oral administration. Tablets are white, elliptical, and film coated. Pfizer also packages the drug in combination with other drugs, such as is the case with its Caduet. In some countries, atorvastatin calcium is made in tablet form by generic drug makers under various brand names including Atorlip, Lipvas, Sortis, Torvast, Torvacard, Totalip, and Tulip. Adverse effectsAs stated earlier, myopathy with elevation of creatinine kinase (CK) and rhabdomyolysis are the most serious, although rare <1
The top best selling drugs are Lipitor, Zocor, Nexium, Prevacid, Advair Diskus etc.Euflexxa Lipitor Actonel Fosamax Effexor Protonix Plavix Celebrex Flomax Nexium Synvisc Prevacid Evista Juvederm Orthovisc Restylane Zyprexa HyalganIf you are buying Lipitor this a definite must see, it shows drastic differences in Lipitor pricing depending on the pharmacy.S. Lovastin tablets are to be taken only under strict medical advice and care.Lipitor is effective at lowering cholesterol but at what cost?A real world drug safety study of Lipitor (atorvastatin calcium) side effects and drug interactions.. The study is based on over 77,000 adverse incidents since 1996 from eHealthMeSometimes bad economic news is actually good news: Pfizer has announced it is acquiring pharmaceutical giant Wyeth in a $68 billion deal that will result in the cutting of 8,000 jobs and the closing of five manufacturing plants.Lipitor is effective at lowering cholesterol but at what cost? It is very expensive and has a long list of side effects.If you like pork, grab yourself a bucket of Lipitor, put on a bib, and prepare to OM NOM NOM on the mother of all bacon projects!Euflexxa Lipitor Actonel Fosamax Effexor Protonix Plavix Celebrex Flomax Nexium Synvisc Prevacid Evista Juvederm Orthovisc Restylane Zyprexa HyalganIf
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Pfizer site for its atorvastatin calcium medication. Features product and prescribing information as well as cholesterol and heart disease resources.
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