FDA label 22b1e468-b2da-49a3-aefa-fc35bc8940c7

5 WARNINGS AND PRECAUTIONS Myopathy and Rhabdomyolysis: Advise patients to promptly report to their physician unexplained and/or persistent muscle pain, tenderness, or weakness. Amlodipine and atorvastatin therapy should be discontinued if myopathy is diagnosed or suspected ( 2 , 5.1 , 8.5 ). Immune-Mediated Necrotizing Myopathy (IMNM): Monitor for myalgia and treat ( 5.2 ). Hepatic Transaminitis: Monitor liver enzymes before and during treatment ( 5.3 ). Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely ( 5.5 ). Angina or myocardial infarction may occur with initiation or dose increase ( 5.4 ). 5.1 Myopathy and Rhabdomyolysis Amlodipine and atorvastatin tablets may cause myopathy (muscle pain, tenderness, or weakness with creatine kinase (CK) above ten times the upper limit of normal) and rhabdomyolysis (with or without acute renal failure secondary to myoglobinuria). Rare fatalities have occurred as a result of rhabdomyolysis with statin use, including amlodipine and atorvastatin tablets. Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher amlodipine and atorvastatin dosage [see Drug Interactions ( 7.3 )] . Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis amlodipine and atorvastatin tablets exposure may be increased by drug interactions due to inhibition of cytochrome P450 enzyme 3A4 (CYP3A4) and/or transporters (e.g., breast cancer resistant protein [BCRP], organic anion-transporting polypeptide [OATP1B1/OATP1B3] and P-glycoprotein [P-gp]), resulting in an increased risk of myopathy and rhabdomyolysis. Concomitant use of cyclosporine, gemfibrozil, tipranavir plus ritonavir or glecaprevir plus pibrentasvir with amlodipine and atorvastatin is not recommended. Amlodipine and atorvastatin dosage modifications are recommended for patients taking certain anti-viral, azole antifungals, or macrolide antibiotic medications [see Dosage and Administration ( 2 )] . Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-administered with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir. Consider if the benefit of use of these products outweighs the increased risk of myopathy and rhabdomyolysis [see Drug Interactions ( 7.3 )] . Concomitant intake of large quantities, more than 1.2 liters daily, of grapefruit juice is not recommended in patients taking amlodipine and atorvastatin tablets [see Drug Interactions ( 7.3 )] . Discontinue amlodipine and atorvastatin tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK increases may resolve if amlodipine and atorvastatin is discontinued. Temporarily discontinue amlodipine and atorvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy). Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the amlodipine and atorvastatin dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. 5.2 Immune-Mediated Necrotizing Myopathy There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Consider risk of IMNM carefully prior to initiation of a different statin. If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM. 5.3 Liver Dysfunction Statins, like atorvastatin, and 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 with atorvastatin 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 dose of atorvastatin. It is recommended that liver enzyme tests be obtained prior to initiating therapy with atorvastatin and repeated as clinically indicated. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including atorvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with amlodipine and atorvastatin tablets, promptly interrupt therapy. If an alternate etiology is not found, do not restart amlodipine and atorvastatin tablets. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of amlodipine and atorvastatin tablets [see Contraindications ( 4 )] . 5.4 Increased Angina and Myocardial Infarction Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. 5.5 Hypotension Symptomatic hypotension is possible with use of amlodipine, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely. 5.6 Endocrine Function Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin. Statins interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production. Clinical studies have shown that atorvastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve. The effects of statins on male fertility have not been studied in adequate numbers of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Avoid a statin with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine. 5.7 CNS Toxicity Brain hemorrhage was seen in a female dog treated with atorvastatin for 3 months at 120 mg/kg/day. Brain hemorrhage and optic nerve vacuolation were seen in another female dog that was sacrificed in moribund condition after 11 weeks of escalating doses up to 280 mg/kg/day. The 120 mg/kg dose resulted in a systemic exposure approximately 16 times the human plasma area-under-the-curve (AUC, 0 to 24 hours) based on the maximum human dose of 80 mg/day. A single tonic convulsion was seen in each of 2 male dogs (one treated at 10 mg/kg/day and one at 120 mg/kg/day) in a 2-year study. No CNS lesions have been observed in mice after chronic treatment for up to 2 years at doses up to 400 mg/kg/day or in rats at doses up to 100 mg/kg/day. These doses were 6 to 11 times (mouse) and 8 to 16 times (rat) the human AUC (0 to 24) based on the maximum recommended human dose (MRHD) of 80 mg/day. CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with other statins. A chemically similar drug in this class produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose. 5.8 Hemorrhagic Stroke In a post-hoc analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study where atorvastatin 80 mg vs. placebo was administered in 4,731 subjects without CHD who had a stroke or TIA within the preceding 6 months, a higher incidence of hemorrhagic stroke was seen in the atorvastatin 80 mg group compared to placebo (55, 2.3% atorvastatin vs. 33, 1.4% placebo; HR: 1.68, 95% CI: 1.09, 2.59; p=0.0168). The incidence of fatal hemorrhagic stroke was similar across treatment groups (17 vs. 18 for the atorvastatin and placebo groups, respectively). The incidence of non-fatal hemorrhagic stroke was significantly higher in the atorvastatin group (38, 1.6%) as compared to the placebo group (16, 0.7%). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the atorvastatin group [see Adverse Reactions ( 6.1 )] .

6 ADVERSE REACTIONS Most common adverse reaction (3% greater than placebo) to amlodipine is edema( 6.1 ). Most common adverse reactions leading to atorvastatin discontinuation were myalgia and diarrhea ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious adverse reactions are discussed in greater detail in other sections of the label: Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1 )] Liver enzyme abnormalities [see Warnings and Precautions ( 5.3 )] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Amlodipine and atorvastatin Amlodipine and atorvastatin tablets has been evaluated for safety in 1,092 patients in double-blind placebo-controlled studies treated for co-morbid hypertension and dyslipidemia. In general, treatment with amlodipine and atorvastatin tablets was well tolerated. For the most part, adverse reactions have been mild or moderate in severity. In clinical trials with amlodipine and atorvastatin tablets, no adverse reactions peculiar to this combination have been observed. Adverse reactions are similar in terms of nature, severity, and frequency to those reported previously with amlodipine and atorvastatin. The following information is based on the clinical experience with amlodipine and atorvastatin. Amlodipine Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine was well tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1,730) at doses up to 10 mg to placebo (N=1,250), discontinuation of amlodipine because of adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most commonly reported side effects more frequent than placebo are dizziness and edema. The incidence (%) of side effects that occurred in a dose-related manner are as follows: Amlodipine 2.5 mg 5 mg 10 mg Placebo N=275 N=296 N=268 N=520 Edema 1.8 3 10.8 0.6 Dizziness 1.1 3.4 3.4 1.5 Flushing 0.7 1.4 2.6 0 Palpitations 0.7 1.4 4.5 0.6 Other adverse reactions that were not clearly dose related but were reported at an incidence greater than 1% in placebo-controlled clinical trials include the following: Amlodipine (%) Placebo (%) (N=1,730) (N=1,250) Fatigue 4.5 2.8 Nausea 2.9 1.9 Abdominal Pain 1.6 0.3 Somnolence 1.4 0.6 Edema, flushing, palpitations, and somnolence appear to be more common in women than in men. The following events occurred in <1% but >0.1% of patients treated with amlodipine in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular : arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis. Central and Peripheral Nervous System : hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo. Gastrointestinal: anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia. General : allergic reaction, asthenia, 2 back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease. Musculoskeletal System : arthralgia, arthrosis, muscle cramps, 2 myalgia. Psychiatric: sexual dysfunction (male 2 and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization. Respiratory System : dyspnea, 2 epistaxis. Skin and Appendages : angioedema, erythema multiforme, pruritus, 2 rash, 2 rash erythematous, rash maculopapular. Special Senses : abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus. Urinary System : micturition frequency, micturition disorder, nocturia. Autonomic Nervous System : dry mouth, sweating increased. Metabolic and Nutritional : hyperglycemia, thirst. Hemopoietic : leukopenia, purpura, thrombocytopenia. 2 These events occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies. Amlodipine therapy has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total TG, TC, HDL-C, uric acid, blood urea nitrogen, or creatinine. Atorvastatin In the atorvastatin placebo-controlled clinical trial database of 16,066 patients (8,755 atorvastatin vs. 7,311 placebo; age range 10 to 93 years, 39% women, 91% Caucasians, 3% Blacks, 2% Asians, 4% other) with a median treatment duration of 53 weeks, 9.7% of patients on atorvastatin and 9.5% of the patients on placebo discontinued because of adverse reactions regardless of causality. The five most common adverse reactions in patients treated with atorvastatin that led to treatment discontinuation and occurred at a rate greater than placebo were: myalgia (0.7%), diarrhea (0.5%), nausea (0.4%), alanine aminotransferase increase (0.4%), and hepatic enzyme increase (0.4%). The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) regardless of causality, in patients treated with atorvastatin in placebo-controlled trials (n=8,755) were: nasopharyngitis (8.3%), arthralgia (6.9%), diarrhea (6.8%), pain in extremity (6%), and urinary tract infection (5.7%). Table 2 summarizes the frequency of clinical adverse reactions, regardless of causality, reported in ≥ 2% and at a rate greater than placebo in patients treated with atorvastatin (n=8,755), from seventeen placebo-controlled trials. Table 2 Clinical Adverse Reactions Occurring in ≥ 2% in Patients Treated with Any Dose of Atorvastatin and at an Incidence Greater than Placebo Regardless of Causality (% of Patients) * Adverse Reaction > 2% in any dose greater than placebo. Adverse Reaction * Any dose N=8,755 10 mg N=3,908 20 mg N=188 40 mg N=604 80 mg N=4,055 Placebo N=7,311 Nasopharyngitis 8.3 12.9 5.3 7 4.2 8.2 Arthralgia 6.9 8.9 11.7 10.6 4.3 6.5 Diarrhea 6.8 7.3 6.4 14.1 5.2 6.3 Pain in extremity 6 8.5 3.7 9.3 3.1 5.9 Urinary tract infection 5.7 6.9 6.4 8 4.1 5.6 Dyspepsia 4.7 5.9 3.2 6 3.3 4.3 Nausea 4 3.7 3.7 7.1 3.8 3.5 Musculoskeletal pain 3.8 5.2 3.2 5.1 2.3 3.6 Muscle spasms 3.6 4.6 4.8 5.1 2.4 3 Myalgia 3.5 3.6 5.9 8.4 2.7 3.1 Insomnia 3 2.8 1.1 5.3 2.8 2.9 Pharyngolaryngeal pain 2.3 3.9 1.6 2.8 0.7 2.1 Other adverse reactions reported in placebo-controlled studies include: Body as a whole: malaise, pyrexia; Digestive system: abdominal discomfort, eructation, flatulence, hepatitis, cholestasis; Musculoskeletal system : musculoskeletal pain, muscle fatigue, neck pain, joint swelling; Metabolic and nutritional system: transaminases increase, liver function test abnormal, blood alkaline phosphatase increase, creatine phosphokinase increase, hyperglycemia; Nervous system: nightmare; Respiratory system: epistaxis; Skin and appendages: urticaria; Special senses: vision blurred, tinnitus; Urogenital system: white blood cells urine positive. Treating to New Targets Study (TNT) In TNT [see Clinical Studies (14.6)] involving 10,001 subjects (age range 29 to 78 years, 19% women; 94.1% Caucasians, 2.9% Blacks, 1% Asians, 2% other) with clinically evident CHD treated with atorvastatin 10 mg daily (n=5,006) or atorvastatin 80 mg daily (n=4,995), serious adverse reactions and discontinuations because of adverse reactions increased with dose. Persistent transaminase elevations (≥ 3 x ULN twice within 4 to 10 days) occurred in 62 (1.3%) individuals with atorvastatin 80 mg and in nine (0.2%) individuals with atorvastatin 10 mg. Elevations of CK (≥ 10 x ULN) were low overall, but were higher in the high-dose atorvastatin treatment group (13, 0.3%) compared to the low-dose atorvastatin group (6, 0.1%). Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) In SPARCL involving 4,731 subjects (age range 21 to 92 years, 40% women; 93.3% Caucasians, 3% Blacks, 0.6% Asians, 3.1% other) without clinically evident CHD but with a stroke or transient ischemic attack (TIA) within the previous 6 months treated with atorvastatin 80 mg (n=2,365) or placebo (n=2,366) for a median follow-up of 4.9 years, there was a higher incidence of persistent hepatic transaminase elevations (≥ 3 x ULN twice within 4 to 10 days) in the atorvastatin group (0.9%) compared to placebo (0.1%). Elevations of CK (>10 x ULN) were rare, but were higher in the atorvastatin group (0.1%) compared to placebo (0%). Diabetes was reported as an adverse reaction in 144 subjects (6.1%) in the atorvastatin group and 89 subjects (3.8%) in the placebo group [see Warnings and Precautions ( 5.6 )] . In a post-hoc analysis, atorvastatin 80 mg reduced the incidence of ischemic stroke (218/2,365, 9.2% vs. 274/2,366, 11.6%) and increased the incidence of hemorrhagic stroke (55/2,365, 2.3% vs. 33/2,366, 1.4%) compared to placebo. The incidence of fatal hemorrhagic stroke was similar between groups (17 atorvastatin vs. 18 placebo). The incidence of non-fatal hemorrhagic strokes was significantly greater in the atorvastatin group (38 non-fatal hemorrhagic strokes) as compared to the placebo group (16 non- fatal hemorrhagic strokes). Subjects who entered the study with a hemorrhagic stroke appeared to be at increased risk for hemorrhagic stroke [7 (16%) atorvastatin vs. 2 (4%) placebo]. There were no significant differences between the treatment groups for all-cause mortality: 216 (9.1%) in the atorvastatin 80 mg/day group vs. 211 (8.9%) in the placebo group. The proportions of subjects who experienced cardiovascular death were numerically smaller in the atorvastatin 80 mg group (3.3%) than in the placebo group (4.1%). The proportions of subjects who experienced non-cardiovascular death were numerically larger in the atorvastatin 80 mg group (5%) than in the placebo group (4%). Adverse Reactions from Clinical Studies of Atorvastatin in Pediatric Patients In a 26-week controlled study in boys and postmenarchal girls with HeFH (ages 10 years to 17 years) (n=140, 31% female; 92% Caucasians, 1.6% Blacks, 1.6% Asians, 4.8% Other), the safety and tolerability profile of atorvastatin 10 to 20 mg daily, as an adjunct to diet to reduce TC, LDL-C, and apo B levels, was generally similar to that of placebo [see Use in Special Populations ( 8.4 ) and Clinical Studies ( 14.11 )]. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval of amlodipine and atorvastatin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Amlodipine The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine. Postmarketing reporting has also revealed a possible association between extrapyramidal disorder and amlodipine. Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles. Atorvastatin Adverse reactions associated with atorvastatin therapy reported since market introduction that are not listed above, regardless of causality assessment, include the following: anaphylaxis, angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), rhabdomyolysis, myositis, fatigue, tendon rupture, fatal and non-fatal hepatic failure, dizziness, depression, peripheral neuropathy, pancreatitis and interstitial lung disease. There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions ( 5.2 ) ]. There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

<table ID="ID54" width="631" styleCode="Noautorules"><col width="151"/><col width="120"/><col width="120"/><col width="114"/><col width="126"/><tbody><tr><td valign="top" styleCode="Lrule Toprule Botrule Rrule"/><td colspan="3" valign="top" styleCode=" Toprule Botrule Rrule" align="center"> Amlodipine </td><td valign="top" styleCode=" Toprule Botrule Rrule"/></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule"/><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.5 mg </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5 mg </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 10 mg </td><td valign="top" styleCode=" Botrule Rrule" align="center"> Placebo </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule"/><td valign="top" styleCode=" Botrule Rrule" align="center"> N=275 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> N=296 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> N=268 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> N=520 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Edema </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 10.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.6 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Dizziness </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.5 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Flushing </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Palpitations </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.5 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.6 </td></tr></tbody></table>

<table ID="ID56" width="0" styleCode="Noautorules"><col width="216"/><col width="192"/><col width="186"/><tbody><tr><td valign="top" styleCode="Lrule Toprule Botrule Rrule"/><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> Amlodipine (%)</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> Placebo (%)</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule"/><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> (N=1,730)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> (N=1,250)</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Fatigue </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.5 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.8 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Nausea </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.9 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Abdominal Pain </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.3 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Somnolence </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.6 </td></tr></tbody></table>

<table ID="ID58" width="100%" styleCode="Noautorules"><caption> Table 2 Clinical Adverse Reactions Occurring in &#x2265; 2% in Patients Treated with Any Dose of Atorvastatin and at an Incidence Greater than Placebo Regardless of Causality (% of Patients) </caption><col width="23%"/><col width="14%"/><col width="15%"/><col width="11%"/><col width="11%"/><col width="11%"/><col width="11%"/><tfoot><tr><td align="left" colspan="7"><paragraph styleCode="Footnote">* Adverse Reaction <content styleCode="underline">&gt;</content> 2% in any dose greater than placebo.</paragraph></td></tr></tfoot><tbody><tr><td valign="top" styleCode="Lrule Toprule Botrule Rrule" align="left"> <content styleCode="bold"> Adverse Reaction^*</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> Any dose N=8,755</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> 10 mg N=3,908</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> 20 mg N=188</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> 40 mg N=604</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> 80 mg N=4,055</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> Placebo N=7,311</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Nasopharyngitis </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 8.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 12.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.2 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 8.2 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Arthralgia </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 8.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 11.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 10.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.5 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Diarrhea </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 7.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 14.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.2 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.3 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Pain in extremity </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 8.5 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 9.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.9 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Urinary tract infection </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.6 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Dyspepsia </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.2 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.3 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Nausea </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 7.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.5 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Musculoskeletal pain </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.2 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.2 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.6 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Muscle spasms </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 4.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Myalgia </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.5 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 8.4 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.1 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Insomnia </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.1 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.9 </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Pharyngolaryngeal pain </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.3 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 3.9 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 1.6 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.8 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0.7 </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 2.1 </td></tr></tbody></table>