FDA label ba63a6f7-e09d-7cae-e053-2995a90a829e

5 WARNINGS AND PRECAUTIONS Myopathy and Rhabdomyolysis: Risks increase when higher doses are used concomitantly with cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, human immunodeficiency virus (HIV) or hepatitis C virus (HCV) protease inhibitors). Predisposing factors include advanced age (> 65), uncontrolled hypothyroidism, and renal impairment. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported. Advise patients to promptly report to their physician unexplained and/or persistent muscle pain, tenderness, or weakness. Atorvastatin calcium tablets therapy should be discontinued if myopathy is diagnosed or suspected ( 2.6 , 5.1 , 8.5 ). Immune-Mediated Necrotizing Myopathy (IMNM): There have been rare reports of 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 ( 5.2 ). Liver enzyme abnormalities: Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter ( 5.3 ). A higher incidence of hemorrhagic stroke was seen in patients without CHD but with stroke or TIA within the previous 6 months in the atorvastatin calcium tablets 80 mg group vs. placebo ( 5.6 ). 5.1 Myopathy and Rhabdomyolysis Atorvastatin calcium 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 atorvastatin calcium 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 atorvastatin calcium tablets dosage [see Drug Interactions ( 7.1 )]. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis Atorvastatin calcium 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 atorvastatin calcium tablets is not recommended. Atorvastatin calcium tablets dosage modifications are recommended for patients taking certain anti-viral, azole antifungals, or macrolide antibiotic medications [see Dosage and Administration ( 2.6 )] . Cases of myopathy/rhabdomyolysis have been reported with atorvastatin coadministered 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 Interaction s ( 7.1 )] . Concomitant intake of large quantities, more than 1.2 liters daily, of grapefruit juice is not recommended in patients taking atorvastatin calcium tablets [see Drug Interactions ( 7.1 )]. Discontinue atorvastatin calcium tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK increases may resolve if atorvastatin calcium tablets is discontinued. Temporarily discontinue atorvastatin calcium tablets 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 atorvastatin calcium tablets 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 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 calcium tablets 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 dose of atorvastatin calcium tablets. It is recommended that liver enzyme tests be obtained prior to initiating therapy with atorvastatin calcium tablets 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 atorvastatin calcium tablets, promptly interrupt therapy. If an alternate etiology is not found, do not restart atorvastatin calcium tablets. Atorvastatin calcium tablets 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 calcium tablets [see Contraindications ( 4 ) ] . 5.4 Endocrine Function Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin calcium tablets. Statins interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production. Clinical studies have shown that atorvastatin calcium tablets 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. Caution should be exercised if a statin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine. 5.5 CNS Toxicity Brain hemorrhage was seen in a female dog treated 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, 0-24 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 (0-24) based on the maximum recommended human dose 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 members of this class. 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. 5.6 Use in Patients with Recent Stroke or TIA In a post-hoc analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study where atorvastatin calcium tablets 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 calcium tablets 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 nonfatal 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 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 ) ] Most common adverse reactions (incidence ≥ 2%) in patients treated with atorvastatin calcium tablets in placebo-controlled trials regardless of causality were: nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at (1-844-834-0530) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the 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. In the atorvastatin calcium tablets placebo-controlled clinical trial database of 16,066 patients (8755 atorvastatin calcium tablets vs. 7311 placebo; age range 10–93 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 calcium tablets and 9.5% of the patients on placebo discontinued due to adverse reactions regardless of causality. The five most common adverse reactions in patients treated with atorvastatin calcium tablets 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 calcium tablets in placebo controlled trials (n=8755) were: nasopharyngitis (8.3%), arthralgia (6.9%), diarrhea (6.8%), pain in extremity (6.0%), 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 calcium tablets (n=8755), from seventeen placebo-controlled trials. Table 2: Clinical Adverse Reactions Occurring in ≥ 2% in Patients Treated with any Dose of Atorvastatin Calcium Tablets and at an Incidence Greater than Placebo Regardless of Causality (% of Patients). Adverse Reaction* Any dose N=8755 10 mg N=3908 20 mg N=188 40 mg N=604 80 mg N=4055 Placebo N=7311 Nasopharyngitis 8.3 12.9 5.3 7.0 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 6.0 8.5 3.7 9.3 3.1 5.9 Urinary tract infection 5.7 6.9 6.4 8.0 4.1 5.6 Dyspepsia 4.7 5.9 3.2 6.0 3.3 4.3 Nausea 4.0 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 3.0 Myalgia 3.5 3.6 5.9 8.4 2.7 3.1 Insomnia 3.0 2.8 1.1 5.3 2.8 2.9 Pharyngolaryngeal pain 2.3 3.9 1.6 2.8 0.7 2.1 * Adverse Reaction ≥ 2% in any dose greater than placebo 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. Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) In ASCOT [see Clinical Studies ( 14.1 ) ] involving 10,305 participants (age range 40–80 years, 19% women; 94.6% Caucasians, 2.6% Africans, 1.5% South Asians, 1.3% mixed/other) treated with atorvastatin calcium tablets 10 mg daily (n=5,168) or placebo (n=5,137), the safety and tolerability profile of the group treated with atorvastatin calcium tablets was comparable to that of the group treated with placebo during a median of 3.3 years of follow-up. Collaborative Atorvastatin Diabetes Study (CARDS) In CARDS [see Clinical Studies ( 14.1 ) ] involving 2,838 subjects (age range 39–77 years, 32% women; 94.3% Caucasians, 2.4% South Asians, 2.3% Afro-Caribbean, 1.0% other) with type 2 diabetes treated with atorvastatin calcium tablets 10 mg daily (n=1,428) or placebo (n=1,410), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 3.9 years. No cases of rhabdomyolysis were reported. Treating to New Targets Study (TNT) In TNT [see Clinical Studies ( 14.1 ) ] involving 10,001 subjects (age range 29–78 years, 19% women; 94.1% Caucasians, 2.9% Blacks, 1.0% Asians, 2.0% other) with clinically evident CHD treated with atorvastatin calcium tablets 10 mg daily (n=5006) or atorvastatin calcium tablets 80 mg daily (n=4995), there were more serious adverse reactions and discontinuations due to adverse reactions in the high-dose atorvastatin group (92, 1.8%; 497, 9.9%, respectively) as compared to the low-dose group (69, 1.4%; 404, 8.1%, respectively) during a median follow-up of 4.9 years. Persistent transaminase elevations (≥3 x ULN twice within 4–10 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%). Incremental Decrease in Endpoints through Aggressive Lipid Lowering Study (IDEAL) In IDEAL [see Clinical Studies ( 14.1 ) ] involving 8,888 subjects (age range 26–80 years, 19% women; 99.3% Caucasians, 0.4% Asians, 0.3% Blacks, 0.04% other) treated with atorvastatin calcium tablets 80 mg/day (n=4439) or simvastatin 20–40 mg daily (n=4449), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 4.8 years. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) In SPARCL involving 4731 subjects (age range 21–92 years, 40% women; 93.3% Caucasians, 3.0% 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 calcium tablets 80 mg (n=2365) or placebo (n=2366) 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– 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 (0.0%). 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 calcium tablets 80 mg reduced the incidence of ischemic stroke (218/2365, 9.2% vs. 274/2366, 11.6%) and increased the incidence of hemorrhagic stroke (55/2365, 2.3% vs. 33/2366, 1.4%) compared to placebo. The incidence of fatal hemorrhagic stroke was similar between groups (17 atorvastatin calcium tablets 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 calcium tablets vs. 2 (4%) placebo]. There were no significant differences between the treatment groups for all-cause mortality: 216 (9.1%) in the atorvastatin calcium tablets 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 calcium tablets 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 calcium tablets 80 mg group (5.0%) than in the placebo group (4.0%). Adverse Reactions from Clinical Studies of A torvastatin Calcium Tablets 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 calcium tablets 10 to 20 mg daily, as an adjunct to diet to reduce total cholesterol, LDL-C, and apo B levels, was generally similar to that of placebo [see Use in Special Populations ( 8.4 ) and Clinical Studies ( 14.6 )] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of atorvastatin calcium tablets. 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. Adverse reactions associated with atorvastatin calcium tablets 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 border="1" cellspacing="0" cellpadding="0"><col width="131.9pt"/><col width="67.8pt"/><col width="67.85pt"/><col width="67.85pt"/><col width="67.8pt"/><col width="67.85pt"/><col width="67.85pt"/><tbody><tr><td><paragraph>Adverse Reaction*</paragraph></td><td styleCode=" Lrule "><paragraph>Any dose</paragraph><paragraph>N=8755</paragraph></td><td styleCode=" Lrule "><paragraph>10 mg</paragraph><paragraph>N=3908</paragraph></td><td styleCode=" Lrule "><paragraph>20 mg</paragraph><paragraph>N=188</paragraph></td><td styleCode=" Lrule "><paragraph>40 mg N=604</paragraph></td><td styleCode=" Lrule "><paragraph>80 mg</paragraph><paragraph>N=4055</paragraph></td><td styleCode=" Lrule "><paragraph>Placebo</paragraph><paragraph>N=7311</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Nasopharyngitis</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>8.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>12.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>7.0</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.2</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>8.2</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Arthralgia</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>8.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>11.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>10.6</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.5</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Diarrhea</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>7.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.4</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>14.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.2</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.3</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Pain in extremity</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.0</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>8.5</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>9.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.9</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Urinary tract infection</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.4</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>8.0</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.6</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Dyspepsia</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.2</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>6.0</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.3</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Nausea</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.0</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>7.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.5</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Musculoskeletal pain</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.2</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.2</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.6</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Muscle Spasms</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.6</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.6</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>4.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.4</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.0</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Myalgia</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.5</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.6</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>8.4</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.1</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Insomnia</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.0</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>1.1</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>5.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.9</paragraph></td></tr><tr><td styleCode=" Toprule "><paragraph>Pharyngolaryngeal pain</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.3</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>3.9</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>1.6</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.8</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>0.7</paragraph></td><td styleCode=" Toprule Lrule "><paragraph>2.1</paragraph></td></tr><tr><td colspan="7" styleCode=" Toprule "><paragraph>* Adverse Reaction &#x2265; 2% in any dose greater than placebo</paragraph></td></tr></tbody></table>