Lipitor (Tablet, Film Coated)

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The patient should be placed on a standard cholesterol-lowering diet before receiving LIPITOR and should continue on this diet during treatment with LIPITOR.<br/>Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb): The recommended starting dose of LIPITOR is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of LIPITOR is 10 to 80 mg once daily. LIPITOR can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of LIPITOR should be individualized according to patient characteristics such as goal of therapy and response (see NCEP Guidelines, summarized in Table 7). After initiation and/or upon titration of LIPITOR,lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly. Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should total-C be used to monitor therapy.<br/>Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10���17 years of age): The recommended starting dose of LIPITOR is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy (see NCEP Pediatric Panel Guidelines, CLINICAL PHARMACOLOGY, and INDICATIONS AND USAGE). Adjustments should be made at intervals of 4 weeks or more.<br/>Homozygous Familial Hypercholesterolemia: The dosage of LIPITOR in patients with homozygous FH is 10 to 80 mg daily. LIPITOR should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.<br/>Concomitant Lipid Lowering Therapy: LIPITOR may be used in combination with a bile acid binding resin for additive effect. The combination of HMG-CoA reductase inhibitors and fibrates should generally be avoided .<br/>Dosage in Patients With Renal Insufficiency: Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin; thus, dosage adjustment in patients with renal dysfunction is not necessary .<br/>Dosage in Patients Taking Cyclosporine, Clarithromycin or A Combination of Ritonavir plus Saquinavir or Lopinavir plus Ritonavir: In patients taking cyclosporine, therapy should be limited to LIPITOR 10 mg once daily. In patients taking clarithromycin or in patients with HIV taking a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, for doses of atorvastatin exceeding 20 mg appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin is employed .

Mechanism of Action: Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Cholesterol and triglycerides circulate in the bloodstream as part of lipoprotein complexes. With ultracentrifugation, these complexes separate into HDL (high-density lipoprotein), IDL (intermediate-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very-low-density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the plasma for delivery to peripheral tissues. LDL is formed from VLDL and is catabolized primarily through the high-affinity LDL receptor. Clinical and pathologic studies show that elevated plasma levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipoprotein B (apo B) promote human atherosclerosis and are risk factors for developing cardiovascular disease, while increased levels of HDL-C are associated with a decreased cardiovascular risk. In animal models, LIPITOR lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL; LIPITOR also reduces LDL production and the number of LDL particles. LIPITOR reduces LDL-C in some patients with homozygous familial hypercholesterolemia (FH), a population that rarely responds to other lipid-lowering medication(s). A variety of clinical studies have demonstrated that elevated levels of total-C, LDL-C, and apo B (a membrane complex for LDL-C) promote human atherosclerosis. Similarly, decreased levels of HDL-C (and its transport complex, apo A) are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C, and inversely with the level of HDL-C. LIPITOR reduces total-C, LDL-C, and apo B in patients with homozygous and heterozygous FH, nonfamilial forms of hypercholesterolemia, and mixed dyslipidemia. LIPITOR also reduces VLDL-C and TG and produces variable increases in HDL-C and apolipoprotein A-1. LIPITOR reduces total-C, LDL-C, VLDL-C, apo B, TG, and non-HDL-C, and increases HDL-C in patients with isolated hypertriglyceridemia. LIPITOR reduces intermediate density lipoprotein cholesterol (IDL-C) in patients with dysbetalipoproteinemia. Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including VLDL, intermediate density lipoprotein (IDL), and remnants, can also promote atherosclerosis. Elevated plasma triglycerides are frequently found in a triad with low HDL-C levels and small LDL particles, as well as in association with non-lipid metabolic risk factors for coronary heart disease. As such, total plasma TG has not consistently been shown to be an independent risk factor for CHD. Furthermore, the independent effect of raising HDL or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.<br/>Pharmacodynamics: Atorvastatin as well as some of its metabolites are pharmacologically active in humans. The liver is the primary site of action and the principal site of cholesterol synthesis and LDL clearance. Drug dosage rather than systemic drug concentration correlates better with LDL-C reduction. Individualization of drug dosage should be based on therapeutic response .<br/>Pharmacokinetics and Drug Metabolism:<br/>Absorption: Atorvastatin is rapidly absorbed after oral administration; maximum plasma concentrations occur within 1 to 2 hours. Extent of absorption increases in proportion to atorvastatin dose. 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 availability is attributed to presystemic clearance in gastrointestinal mucosa and/or hepatic first-pass metabolism. Although food decreases the rate and extent of drug absorption by approximately 25% and 9%, respectively, as assessed by Cmax and AUC, LDL-C reduction is similar whether atorvastatin is given with or without food. Plasma atorvastatin concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning. However, LDL-C reduction is the same regardless of the time ofday of drug administration .<br/>Distribution: Mean volume of distribution of atorvastatin is approximately 381 liters. Atorvastatin is���98% bound to plasma proteins. A blood/plasma ratio of approximately 0.25 indicates poor drug penetration into red blood cells. Based on observations in rats, atorvastatin is likely to be secreted in human milk .<br/>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. In vitro studies suggest the importance of atorvastatin metabolism by cytochrome P450 3A4, consistent with increased plasma concentrations of atorvastatin in humans following coadministration with erythromycin, a known inhibitor of this isozyme . In animals, the ortho-hydroxy metabolite undergoes further glucuronidation.<br/>Excretion: Atorvastatin and its metabolites are eliminated primarily in bile following hepatic and/or extra-hepatic metabolism; however, the drug does not appear to undergo enterohepatic recirculation. Mean plasma elimination half-life of atorvastatin in humans is approximately 14 hours, but the half-life of inhibitory activity for HMG-CoA reductase is 20 to 30 hours due to the contribution of active metabolites. Less than 2% of a dose of atorvastatin is recovered in urine following oral administration.<br/>Special Populations:<br/>Geriatric: Plasma concentrations of atorvastatin are higher (approximately 40% for Cmax and 30% for AUC) in healthy elderly subjects (age���65 years) than in young adults. Clinical data suggest a greater degree of LDL-lowering at any dose of drug in the elderly patient population compared to younger adults .<br/>Pediatric: Pharmacokinetic data in the pediatric population are not available.<br/>Gender: Plasma concentrations of atorvastatin in women differ from those in men (approximately 20% higher for Cmax and 10% lower for AUC); however, there is no clinically significant difference in LDL-C reduction with LIPITOR between men and women.<br/>Renal Insufficiency: Renal disease has no influence on the plasma concentrations or LDL-C reduction of atorvastatin; thus, dose adjustment in patients with renal dysfunction is not necessary .<br/>Hemodialysis: While studies have not been conducted in patients with end-stage renal disease, hemodialysis is not expected to significantly enhance clearance of atorvastatin since the drug is extensively bound to plasma proteins.<br/>Hepatic Insufficiency: In patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin are markedly increased. Cmax and AUC are each 4-fold greater in patients with Childs-Pugh A disease. Cmax and AUC are approximately 16-fold and 11-fold increased, respectively, in patients with Childs-Pugh B disease .<br/>Clinical Studies:<br/>Prevention of Cardiovascular Disease: In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), the effect of LIPITOR (atorvastatin calcium) on fatal and non-fatal coronary heart disease was assessed in 10,305 hypertensive patients 40���80 years of age (mean of 63 years), without a previous myocardial infarction and with TC levels���251 mg/dl (6.5 mmol/l). Additionally all patients had at least 3 of the following cardiovascular risk factors: male gender (81.1%), age>55 years (84.5%), smoking (33.2%), diabetes (24.3%), history of CHD in a first-degree relative (26%), TC:HDL>6 (14.3%), peripheral vascular disease (5.1%), left ventricular hypertrophy (14.4%), prior cerebrovascular event (9.8%), specific ECG abnormality (14.3%), proteinuria/albuminuria (62.4%). In this double-blind, placebo-controlled study patients were treated with anti-hypertensive therapy (Goal BP<140/90 mm Hg for non-diabetic patients,<130/80 mm Hg for diabetic patients) and allocated to either LIPITOR 10 mg daily (n=5168) or placebo (n=5137), using a covariate adaptive method which took into account the distribution of nine baseline characteristics of patients already enrolled and minimized the imbalance of those characteristics across the groups. Patients were followed for a median duration of 3.3 years. The effect of 10 mg/day of LIPITOR on lipid levels was similar to that seen in previous clinical trials. LIPITOR significantly reduced the rate of coronary events [either fatal coronary heart disease (46 events in the placebo group vs. 40 events in the LIPITOR group) or nonfatal MI (108 events in the placebo group vs. 60 events in the LIPITOR group)] with a relative risk reduction of 36% [(based on incidences of 1.9% for LIPITOR vs. 3.0% for placebo), p=0.0005 (see Figure 1)]. The risk reduction was consistent regardless of age, smoking status, obesity or presence of renal dysfunction. The effect of LIPITOR was seen regardless of baseline LDL levels. Due to the small number of events, results for women were inconclusive. Figure 1: Effect of LIPITOR 10 mg/day on Cumulative Incidence of Nonfatal Myocardial Infarction or Coronary Heart Disease Death (in ASCOT-LLA) LIPITOR also significantly decreased the relative risk for revascularization procedures by 42%. Although the reduction of fatal and non-fatal strokes did not reach a pre-defined significance level (p=0.01), a favorable trend was observed with a 26% relative risk reduction (incidences of 1.7% for LIPITOR and 2.3% for placebo). There was no significant difference between the treatment groups for death due to cardiovascular causes (p=0.51) or noncardiovascular causes (p=0.17). In the Collaborative Atorvastatin Diabetes Study (CARDS), the effect of LIPITOR (atorvastatin calcium) on cardiovascular disease (CVD) endpoints was assessed in 2838 subjects (94% White, 68% male), ages 40���75 with type 2 diabetes based on WHO criteria, without prior history of cardiovascular disease and with LDL���160 mg/dL and TG���600 mg/dL. In addition to diabetes, subjects had 1 or more of the following risk factors: current smoking (23%), hypertension (80%), retinopathy (30%), or microalbuminuria (9%) or macroalbuminuria (3%). No subjects on hemodialysis were enrolled in the study. In this multicenter, placebo-controlled, double-blind clinical trial, subjects were randomly allocated to either LIPITOR 10 mg daily (1429) or placebo (1411) in a 1:1 ratio and were followed for a median duration of 3.9 years. The primary endpoint was the occurrence of any of the major cardiovascular events: myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke. The primary analysis was the time to first occurrence of the primary endpoint. Baseline characteristics of subjects were: mean age of 62 years, mean HbA7.7%; median LDL-C 120 mg/dL; median TC 207 mg/dL; median TG 151 mg/dL; median HDL-C 52mg/dL. The effect of LIPITOR 10 mg/ day on lipid levels was similar to that seen in previous clinical trials. LIPITOR significantly reduced the rate of major cardiovascular events (primary endpoint events) (83 events in the LIPITOR group vs. 127 events in the placebo group) with a relative risk reduction of 37%, HR 0.63, 95% CI (0.48,0.83) (p=0.001) (see Figure 2). An effect of LIPITOR was seen regardless of age, sex, or baseline lipid levels. Figure 2. Effect of LIPITOR 10 mg/day on Time to Occurrence of Major Cardiovascular Event (myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke) in CARDS. LIPITOR significantly reduced the risk of stroke by 48% (21 events in the LIPITOR group vs 39 events in the placebo group), HR 0.52, 95% CI (0.31,0.89) (p=0.016) and reduced the risk of MI by 42% (38 events in the LIPITOR group vs 64 events in the placebo group), HR 0.58, 95.1% CI (0.39, 0.86) (p=0.007). There was no significant difference between the treatment groups for angina, revascularization procedures, and acute CHD death. There were 61 deaths in the LIPITOR group vs 82 deaths in the placebo group, (HR 0.73, p=0.059). In the Treating to New Targets Study (TNT), the effect of LIPITOR 80 mg/day vs. LIPITOR 10 mg/day on the reduction in cardiovascular events was assessed in 10,001 subjects (94% white, 81% male, 38%���65 years) with clinically evident coronary heart disease who had achieved a target LDL-C level<130 mg/dL after completing an 8-week, open-label, run-in period with LIPITOR 10 mg/day. Subjects were randomly assigned to either 10 mg/day or 80 mg/day of LIPITOR and followed for a median duration of 4.9 years. The primary endpoint was the time-to-first occurrence of any of the following major cardiovascular events (MCVE): death due to CHD, non-fatal myocardial infarction, resuscitated cardiac arrest, and fatal and non-fatal stroke. The mean LDL-C, TC, TG, non-HDL and HDL cholesterol levels at 12 weeks were 73, 145, 128, 98 and 47 mg/dL during treatment with 80 mg of LIPITOR and 99, 177, 152, 129 and 48 mg/dL during treatment with 10 mg of LIPITOR. Treatment with LIPITOR 80 mg/day significantly reduced the rate of MCVE (434 events in the 80mg/day group vs 548 events in the 10 mg/day group) with a relative risk reduction of 22%, HR 0.78, 95% CI (0.69,0.89), p=0.0002 (see Figure 3 and Table 1). The overall risk reduction was consistent regardless of age (<65,���65) or gender. Figure 3. Effect of LIPITOR 80 mg/day vs.10 mg/day on Time to Occurrence of Major Cardiovascular Events (TNT) Of the events that comprised the primary efficacy endpoint, treatment with LIPITOR 80 mg/day significantly reduced the rate of nonfatal, non-procedure related MI and fatal and non-fatal stroke, but not CHD death or resuscitated cardiac arrest (Table 1). Of the predefined secondary endpoints, treatment with LIPITOR 80 mg/day significantly reduced the rate of coronary revascularization, angina and hospitalization for heart failure, but not peripheral vascular disease. The reduction in the rate of CHF with hospitalization was only observed in the 8% of patients with a prior history of CHF. There was no significant difference between the treatment groups for all-cause mortality (Table 1). The proportions of subjects who experienced cardiovascular death, including the components of CHD death and fatal stroke were numerically smaller in the LIPITOR 80 mg group than in the LIPITOR 10 mg treatment group. The proportions of subjects who experienced noncardiovascular death were numerically larger in the LIPITOR 80 mg group than in the LIPITOR 10 mg treatment group. In the Incremental Decrease in Endpoints Through Aggressive Lipid Lowering Study (IDEAL), treatment with LIPITOR 80 mg/day was compared to treatment with simvastatin 20���40 mg/day in 8,888 subjects up to 80 years of age with a history of CHD to assess whether reduction in CV risk could be achieved. Patients were mainly male (81%), white (99%) with an average age of 61.7 years, and an average LDL-C of 121.5 mg/dL at randomization; 76% were on statin therapy. In this prospective, randomized, open-label, blinded endpoint (PROBE) trial with no run-in period, subjects were followed for a median duration of 4.8 years. The mean LDL-C, TC, TG, HDL and non-HDL cholesterol levels at Week 12 were 78, 145, 115, 45 and 100 mg/dL during treatment with 80 mg of LIPITOR and 105, 179, 142, 47 and 132 mg/dL during treatment with 20���40 mg of simvastatin. There was no significant difference between the treatment groups for the primary endpoint, the rate of first major coronary event (fatal CHD, nonfatal MI and resuscitated cardiac arrest): 411 (9.3%) in the LIPITOR 80 mg/day group vs. 463 (10.4%) in the simvastatin 20���40 mg/day group, HR 0.89, 95% CI ( 0.78,1.01), p=0.07. There were no significant differences between the treatment groups for all-cause mortality: 366 (8.2%) in the LIPITOR 80 mg/day group vs. 374 (8.4%) in the simvastatin 20���40 mg/day group. The proportions of subjects who experienced CV or non-CV death were similar for the LIPITOR 80 mg group and the simvastatin 20���40 mg group.<br/>Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb): LIPITOR reduces total-C, LDL-C, VLDL-C, apo B, and TG, and increases HDL-C in patients with hypercholesterolemia and mixed dyslipidemia. Therapeutic response is seen within 2 weeks, and maximum response is usually achieved within 4 weeks and maintained during chronic therapy. LIPITOR is effective in a wide variety of patient populations with hypercholesterolemia, with and without hypertriglyceridemia, in men and women, and in the elderly. Experience in pediatric patients has been limited to patients with homozygous FH. In two multicenter, placebo-controlled, dose-response studies in patients with hypercholesterolemia, LIPITOR given as a single dose over 6 weeks significantly reduced total-C, LDL-C, apo B, and TG (Pooled results are provided in Table 2). In patients with Fredrickson Types IIa and IIb hyperlipoproteinemia pooled from 24 controlled trials, the median (25and 75percentile) percent changes from baseline in HDL-C for atorvastatin 10, 20, 40, and 80 mg were 6.4 (-1.4, 14), 8.7(0, 17), 7.8(0, 16), and 5.1 (-2.7, 15), respectively. Additionally, analysis of the pooled data demonstrated consistent and significant decreases in total-C, LDL-C, TG, total-C/HDL-C, and LDL-C/HDL-C. In three multicenter, double-blind studies in patients with hypercholesterolemia, LIPITOR was compared to other HMG-CoA reductase inhibitors. After randomization, patients were treated for 16 weeks with either LIPITOR 10 mg per day or a fixed dose of the comparative agent (Table 3). The impact on clinical outcomes of the differences in lipid-altering effects between treatments shown in Table 3 is not known. Table 3 does not contain data comparing the effects of atorvastatin 10 mg and higher doses of lovastatin, pravastatin, and simvastatin. The drugs compared in the studies summarized in the table arenot necessarily interchangeable.<br/>Hypertriglyceridemia (Fredrickson Type IV): The response to LIPITOR in 64 patients with isolated hypertriglyceridemia treated across several clinical trials is shown in the table below. For the atorvastatin-treated patients, median (min, max) baseline TG level was 565 (267���1502).<br/>Dysbetalipoproteinemia (Fredrickson Type III): The results of an open-label crossover study of 16 patients (genotypes: 14 apo E2/E2 and 2 apo E3/E2) with dysbetalipoproteinemia (Fredrickson Type III) are shown in the table below.<br/>Homozygous Familial Hypercholesterolemia: In a study without a concurrent control group, 29 patients ages 6 to 37 years with homozygous FH received maximum daily doses of 20 to 80 mg of LIPITOR. The mean LDL-C reduction in this study was 18%. Twenty-five patients with a reduction in LDL-C had a mean response of 20% (range of 7% to 53%, median of 24%); the remaining 4 patients had 7% to 24% increases in LDL-C. Five of the 29 patients had absent LDL-receptor function. Of these, 2 patients also had a portacaval shunt and had nosignificant reduction in LDL-C. The remaining 3 receptor-negative patients had a mean LDL-C reduction of 22%.<br/>Heterozygous Familial Hypercholesterolemia in Pediatric Patients: In a double-blind, placebo-controlled study followed by an open-label phase, 187 boys and postmenarchal girls 10���17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (FH) or severe hypercholesterolemia were randomized to LIPITOR (n=140) or placebo (n=47) for 26 weeks and then all received LIPITOR for 26 weeks. Inclusion in the study required 1) a baseline LDL-C level���190 mg/dL or 2) a baseline LDL-C���160 mg/dL and positive family history of FH or documented premature cardiovascular disease in a first- or second-degree relative. The mean baseline LDL-C value was 218.6 mg/dL (range: 138.5���385.0 mg/dL) in the LIPITOR group compared to 230.0 mg/dL (range: 160.0���324.5 mg/dL) in the placebo group. The dosage of LIPITOR (once daily) was 10 mg for the first 4 weeks and up-titrated to 20 mg if the LDL-C level was>130 mg/dL. The number of LIPITOR-treated patients who required up-titration to 20 mg after Week 4 during the double-blind phase was 80 (57.1%). LIPITOR significantly decreased plasma levels of total-C, LDL-C, triglycerides, and apolipoprotein B during the 26 week double-blind phase (see Table 6). The mean achieved LDL-C value was 130.7 mg/dL (range: 70.0���242.0 mg/dL) in the LIPITOR group compared to 228.5 mg/dL (range: 152.0���385.0 mg/dL) in the placebo group during the 26 week double-blind phase. The safety and efficacy of doses above 20 mg have not been studied in controlled trials in children. The long-term efficacy of LIPITOR therapy in childhood to reduce morbidity and mortality in adulthood has not been established.

LIPITOR (atorvastatin calcium) is supplied as white, elliptical, film-coated tablets of atorvastatin calcium containing 10, 20, 40 and 80 mg atorvastatin. 10 mg tablets: coded "PD 155" on one side and "10" on the other. NDC 0071-0155-23 bottles of 90 NDC 0071-0155-34 bottles of 5000 NDC 0071-0155-40 10��10 unit dose blisters 20 mg tablets: coded "PD 156" on one side and "20" on the other. NDC 0071-0156-23 bottles of 90 NDC 0071-0156-40 10��10 unit dose blisters NDC 0071-0156-94 bottles of 5000 40 mg tablets: coded "PD 157" on one side and "40" on the other. NDC 0071-0157-23 bottles of 90 NDC 0071-0157-73 bottles of 500 NDC 0071-0157-88 bottles of 2500 NDC 0071-0157-40 10��10 unit dose blisters 80 mg tablets: coded "PD 158" on one side and "80" on the other. NDC 0071-0158-23 bottles of 90 NDC 0071-0158-73 bottles of 500 NDC 0071-0158-88 bottles of 2500 NDC 0071-0158-92 8��8 unit dose blisters<br/>Storage: Store at controlled room temperature 20���25��C (68���77��F) [see USP]. Rx Only

dailymed-ingredient:Opadry_White_YS-1-7040, dailymed-ingredient:calcium_carbonate, dailymed-ingredient:candelilla_wax, dailymed-ingredient:croscarmellose_sodium, dailymed-ingredient:hydroxypropyl_cellulose, dailymed-ingredient:hypromellose, dailymed-ingredient:lactose_monohydrate, dailymed-ingredient:magnesium_stearate, dailymed-ingredient:microcrystalline_cellulose, dailymed-ingredient:polyethylene_glycol, dailymed-ingredient:polysorbate_80, dailymed-ingredient:simethicone_emulsion, dailymed-ingredient:talc, dailymed-ingredient:titanium_dioxide

There is no specific treatment for atorvastatin overdosage. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.

Lipitor (Tablet, Film Coated)

Liver Dysfunction: HMG-CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevations (>3 times the upper limit of normal [ULN] occurring on 2 or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively. One patient in clinical trials developed jaundice. Increases in liver function tests (LFT) in other patients were not associated with jaundice or other clinical signs or symptoms. Upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels without sequelae. Eighteen of 30 patients with persistent LFT elevations continued treatment with a reduced doseof atorvastatin. It is recommended that liver function tests be performed prior to and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter. Liver enzyme changes generally occur in the first 3 months of treatment with atorvastatin. Patients who develop increased transaminase levels should be monitored until the abnormalities resolve. Should an increase in ALT or AST of>3 times ULN persist, reduction of dose or withdrawal of atorvastatin is recommended. Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of atorvastatin .<br/>Skeletal Muscle: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin and with other drugs in this class. Uncomplicated myalgia has been reported in atorvastatin-treated patients . Myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values>10 times ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. The risk of myopathy during treatment with drugs in this class is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or lopinavir plus ritonavir, niacin, or azole antifungals. Physicians considering combined therapy with atorvastatin and fibric acid derivatives, erythromycin, clarithromycin, a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, immunosuppressive drugs, azole antifungals, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Lower starting and maintenance doses of atorvastatin should be considered when taken concomitantly with the aforementioned drugs . Periodic creatine phosphokinase (CPK) determinations may be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence ofsevere myopathy. Atorvastatin therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).

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Lipitor