FDA label b267a9e3-5e2c-4674-9f42-4df71ae69dcc

5 WARNINGS AND PRECAUTIONS Myopathy and rhabdomyolysis have been reported in patients taking fenofibrate. The risks for myopathy and rhabdomyolysis are increased when fibrates are co-administered with a statin (with a significantly higher rate observed for gemfibrozil), particularly in elderly patients and patients with diabetes, renal failure, or hypothyroidism ( 5.1 ). Trilipix can increase serum transaminases. Liver tests should be monitored periodically ( 5.3 ). Trilipix can reversibly increase serum creatinine levels ( 5.2 ). Renal function should be monitored periodically in patients with renal insufficiency ( 8.6 ). Trilipix increases cholesterol excretion into the bile, leading to risk of cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated ( 5.4 ). Exercise caution in concomitant treatment with oral coumarin anticoagulants. Adjust the dosage of coumarin anticoagulant to maintain the prothrombin time/INR at the desired level to prevent bleeding complications ( 5.5 ). 5.1 Skeletal Muscle Fibrate and statin monotherapy increase the risk of myositis or myopathy, and have been associated with rhabdomyolysis. Data from observational studies suggest that the risk for rhabdomyolysis is increased when fibrates are co-administered with a statin (with a significantly higher rate observed for gemfibrozil). Refer to the respective statin labeling for important drug-drug interactions that increase statin levels and could increase this risk. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal failure, or hypothyroidism. Myalgia was reported in 3.3% of patients treated with Trilipix monotherapy and 3.1% to 3.5% of patients treated with Trilipix co-administered with statins compared to 4.7% to 6.1% of patients treated with statin monotherapy. Increases in creatine phosphokinase (CPK) to > 5 times upper limit of normal occurred in no patients treated with Trilipix monotherapy and 0.2% to 1.2% of patients treated with Trilipix co-administered with statins compared to 0.4% to 1.3% of patients treated with statin monotherapy. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of CPK levels. Patients should promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and Trilipix and statin therapy should be discontinued if markedly elevated CPK levels occur or myopathy or myositis is diagnosed. 5.2 Serum Creatinine Reversible elevations in serum creatinine have been reported in patients receiving Trilipix as monotherapy or co-administered with statins as well as patients receiving fenofibrate. In the pooled analysis of three double-blind controlled studies of Trilipix administered as monotherapy or in combination with statins, increases in creatinine to > 2 mg/dL occurred in 0.8% of patients treated with Trilipix monotherapy and 1.1% to 1.3% of patients treated with Trilipix co-administered with statins compared to 0% to 0.4% of patients treated with statin monotherapy. Elevations in serum creatinine were generally stable over time with no evidence for continued increases in serum creatinine with long-term therapy and tended to return to baseline following discontinuation of treatment. The clinical significance of these observations is unknown. Monitoring renal function in patients with renal impairment taking Trilipix is suggested. Renal monitoring should be considered for patients at risk for renal insufficiency, such as the elderly and those with diabetes. 5.3 Liver Function Trilipix at a dose of 135 mg once daily administered as monotherapy or co-administered with low to moderate doses of statins has been associated with increases in serum transaminases [AST (SGOT) or ALT (SGPT)]. In a pooled analysis of three double-blind controlled studies of Trilipix administered as monotherapy or in combination with statins, increases to > 3 times the upper limit of normal on two consecutive occasions in ALT and AST occurred in 1.9% and 0.2%, respectively, of patients receiving Trilipix monotherapy and in 1.3% and 0.4%, respectively, of patients receiving Trilipix co-administered with statins. Increases to > 3 times the upper limit of normal in ALT and AST occurred in no patients receiving low- to moderate-dose statin monotherapy. Increases to > 3 times the upper limit of normal in ALT and AST occurred in 0.8% and 0.4%, respectively in patients receiving high-dose statin monotherapy. In a long-term study of Trilipix co-administered with statins for up to 52 weeks, increases of > 3 times the upper limit of normal on two consecutive occasions of ALT and AST occurred in 1.2% and 0.5% of patients, respectively. When transaminase determinations were followed either after discontinuation of treatment or during continued treatment, a return to normal limits was usually observed. Increases in ALT and/or AST were not accompanied by increases in bilirubin or clinically significant increases in alkaline phosphatase. In a pooled analysis of 10 placebo-controlled trials of fenofibrate, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking fenofibrate versus 1.1% of patients treated with placebo. The incidence of increases in transaminases observed with fenofibrate therapy may be dose related. In an 8-week dose-ranging study of fenofibrate in hypertriglyceridemia, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 90 mg to 135 mg Trilipix once daily and was 0% in those receiving dosages equivalent to 45 mg Trilipix once daily or less, or placebo. Hepatocellular, chronic active, and cholestatic hepatitis observed with fenofibrate therapy have been reported after exposures of weeks to several years. In extremely rare cases, cirrhosis has been reported in association with chronic active hepatitis. Regular monitoring of liver function, including serum ALT (SGPT) should be performed for the duration of therapy with Trilipix, and therapy discontinued if enzyme levels persist above 3 times the upper limit of normal. 5.4 Cholelithiasis Trilipix, like fenofibrate, clofibrate, and gemfibrozil, may increase cholesterol excretion into the bile, potentially leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Trilipix therapy should be discontinued if gallstones are found. 5.5 Concomitant Oral Anticoagulants Caution should be exercised when Trilipix is given in conjunction with oral coumarin anticoagulants. Trilipix may potentiate the anticoagulant effects of these agents resulting in prolongation of the prothrombin time/INR. Frequent monitoring of prothrombin time/INR and dose adjustment of the oral anticoagulant are recommended until the prothrombin time/INR has stabilized in order to prevent bleeding complications. 5.6 Pancreatitis Pancreatitis has been reported in patients taking drugs of the fibrate class, including Trilipix. This occurrence may represent a failure of efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation with obstruction of the common bile duct. 5.7 Hypersensitivity Reactions Acute hypersensitivity reactions including severe skin rashes requiring patient hospitalization and treatment with steroids have occurred very rarely during treatment with fenofibrate, including rare spontaneous reports of Stevens-Johnson Syndrome and toxic epidermal necrolysis. 5.8 Hematological Changes Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of Trilipix and fenofibrate therapy. Extremely rare spontaneous reports of thrombocytopenia and agranulocytosis have been received with fenofibrate therapy. 5.9 Mortality and Coronary Heart Disease Morbidity The effect of Trilipix on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established. Because of similarities between Trilipix and fenofibrate, clofibrate, and gemfibrozil, the findings in the following large randomized, placebo-controlled clinical studies with these fibrate drugs may also apply to Trilipix. The Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) trial was a randomized placebo-controlled study of 5518 patients with type 2 diabetes mellitus on background statin therapy treated with fenofibrate. The mean duration of follow-up was 4.7 years. Fenofibrate plus statin combination therapy showed a non-significant 8% relative risk reduction in the primary outcome of major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular disease death (hazard ratio [HR] 0.92, 95% CI 0.79-1.08) (p=0.32) as compared to statin monotherapy. In a gender subgroup analysis, the hazard ratio for MACE in men receiving combination therapy versus statin monotherapy was 0.82 (95% CI 0.69-0.99), and the hazard ratio for MACE in women receiving combination therapy versus statin monotherapy was 1.38 (95% CI 0.98-1.94) (interaction p=0.01). The clinical significance of this subgroup finding is unclear. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year randomized, placebo-controlled study of 9795 patients with type 2 diabetes mellitus treated with fenofibrate. Fenofibrate demonstrated a non-significant 11% relative reduction in the primary outcome of coronary heart disease events (hazard ratio [HR] 0.89, 95% CI 0.75-1.05, p = 0.16) and a significant 11% reduction in the secondary outcome of total cardiovascular disease events (HR 0.89 [0.80-0.99], p = 0.04). There was a non-significant 11% (HR 1.11 [0.95, 1.29], p = 0.18) and 19% (HR 1.19 [0.90, 1.57], p = 0.22) increase in total and coronary heart disease mortality, respectively, with fenofibrate as compared to placebo. In the Coronary Drug Project, a large study of post-myocardial infarction patients treated for 5 years with clofibrate, there was no difference in mortality seen between the clofibrate group and the placebo group. There was, however, a difference in the rate of cholelithiasis and cholecystitis requiring surgery between the two groups (3.0% vs. 1.8%). In a study conducted by the World Health Organization (WHO), 5000 subjects without known coronary artery disease were treated with placebo or clofibrate for 5 years and followed for an additional one year. There was a statistically significant, higher age-adjusted all-cause mortality in the clofibrate group compared with the placebo group (5.70% vs. 3.96%, p = < 0.01). Excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis. This appeared to confirm the higher risk of gallbladder disease seen in clofibrate-treated patients studied in the Coronary Drug Project. The Helsinki Heart Study was a large (N = 4081) study of middle-aged men without a history of coronary artery disease. Subjects received either placebo or gemfibrozil for 5 years, with a 3.5 year open extension afterward. Total mortality was numerically higher in the gemfibrozil randomization group but did not achieve statistical significance (p = 0.19, 95% confidence interval for relative risk G:P = 0.91-1.64). Although cancer deaths trended higher in the gemfibrozil group (p = 0.11), cancers (excluding basal cell carcinoma) were diagnosed with equal frequency in both study groups. Due to the limited size of the study, the relative risk of death from any cause was not shown to be different than that seen in the 9 year follow-up data from WHO study (RR = 1.29). A secondary prevention component of the Helsinki Heart Study enrolled middle-aged men excluded from the primary prevention study because of known or suspected coronary heart disease. Subjects received gemfibrozil or placebo for 5 years. Although cardiac deaths trended higher in the gemfibrozil group, this was not statistically significant (hazard ratio 2.2, 95% confidence interval: 0.94-5.05). 5.10 Venothromboembolic Disease In the FIELD trial, pulmonary embolus (PE) and deep vein thrombosis (DVT) were observed at higher rates in the fenofibrate- than the placebo-treated group. Of 9,795 patients enrolled in FIELD, there were 4,900 in the placebo group and 4,895 in the fenofibrate group. For DVT, there were 48 events (1%) in the placebo group and 67 (1%) in the fenofibrate group (p = 0.074); and for PE, there were 32 (0.7%) events in the placebo group and 53 (1%) in the fenofibrate group (p = 0.022). In the Coronary Drug Project, a higher proportion of the clofibrate group experienced definite or suspected fatal or nonfatal PE or thrombophlebitis than the placebo group (5.2% vs. 3.3% at five years; p < 0.01).

6 ADVERSE REACTIONS The most common adverse events (≥ 3% of patients receiving Trilipix or Trilipix co-administered with statins) are headache, back pain, nasopharyngitis, nausea, myalgia, diarrhea, and upper respiratory tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Abbott Laboratories at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse event rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug. Trilipix (fenofibric acid) Monotherapy Treatment-emergent adverse events reported in 3% or more of patients treated with Trilipix during the randomized controlled trials are listed in Table 1 below. Co-Administration Therapy with Statins (Double-blind Controlled Trials) Treatment-emergent adverse events reported in 3% or more of patients treated with Trilipix co-administered with statins during the randomized controlled trials are listed in Table 1 below. Table 1.Treatment-Emergent Adverse Events Reported in ≥ 3% of Patients Receiving Trilipix or Trilipix Co-Administered with a Statin During Double-Blind Controlled Studies [Number (%)] Adverse Event Trilipix (N = 490) Low-Dose Statin (N = 493) Trilipix + Low-Dose Statin (N = 490) Moderate-Dose Statin (N = 491) Trilipix + Moderate-Dose Statin (N = 489) High-Dose Statin (N = 245) Gastrointestinal Disorders Constipation 16 (3.3) 11 (2.2) 16 (3.3) 13 (2.6) 15 (3.1) 6 (2.4) Diarrhea 19 (3.9) 16 (3.2) 15 (3.1) 24 (4.9) 18 (3.7) 17 (6.9) Dyspepsia 18 (3.7) 13 (2.6) 13 (2.7) 17 (3.5) 23 (4.7) 6 (2.4) Nausea 21 (4.3) 18 (3.7) 17 (3.5) 22 (4.5) 27 (5.5) 10 (4.1) General Disorders and Administration Site Conditions Fatigue 10 (2.0) 13 (2.6) 13 (2.7) 13 (2.6) 16 (3.3) 5 (2.0) Pain 17 (3.5) 9 (1.8) 16 (3.3) 8 (1.6) 7 (1.4) 8 (3.3) Infections and Infestations Nasopharyngitis 17 (3.5) 29 (5.9) 23 (4.7) 16 (3.3) 21 (4.3) 9 (3.7) Sinusitis 16 (3.3) 4 (0.8) 14 (2.9) 8 (1.6) 17 (3.5) 4 (1.6) Upper Respiratory Tract Infection 26 (5.3) 13 (2.6) 18 (3.7) 23 (4.7) 23 (4.7) 7 (2.9) Investigations ALT Increased 6 (1.2) 2 (0.4) 15 (3.1) 2 (0.4) 12 (2.5) 4 (1.6) Musculoskeletal and Connective Tissue Disorders Arthralgia 19 (3.9) 22 (4.5) 21 (4.3) 21 (4.3) 17 (3.5) 12 (4.9) Back Pain 31 (6.3) 31 (6.3) 30 (6.1) 32 (6.5) 20 (4.1) 8 (3.3) Muscle Spasms 8 (1.6) 18 (3.7) 12 (2.4) 24 (4.9) 15 (3.1) 6 (2.4) Myalgia 16 (3.3) 24 (4.9) 17 (3.5) 23 (4.7) 15 (3.1) 15 (6.1) Pain in Extremity 22 (4.5) 24 (4.9) 14 (2.9) 21 (4.3) 13 (2.7) 9 (3.7) Nervous System Disorders Dizziness 20 (4.1) 8 (1.6) 19 (3.9) 11 (2.2) 16 (3.3) 2 (0.8) Headache 62 (12.7) 64 (13.0) 64 (13.1) 82 (16.7) 58 (11.9) 32 (13.1) Low-dose statin = rosuvastatin 10 mg, simvastatin 20 mg, or atorvastatin 20 mg Moderate-dose statin = rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg High-dose statin = rosuvastatin 40 mg, simvastatin 80 mg, or atorvastatin 80 mg Co-Administration Therapy with Statins (Long-Term Exposure for up to 64 Weeks) Patients successfully completing any one of the three double-blind, controlled studies were eligible to participate in a 52-week long-term extension study where they received Trilipix co-administered with the moderate dose statin. A total of 2201 patients received at least one dose of Trilipix co-administered with a statin in the double-blind controlled study or the long-term extension study for up to a total of 64 weeks of treatment. Additional treatment-emergent adverse events (not listed in Table 1 above) reported in 3% or more of patients receiving Trilipix co-administered with a statin in either the double-blind controlled studies or the long-term extension study are provided below. Infections and Infestations Bronchitis, influenza, and urinary tract infection. Investigations AST increased, blood CPK increased, and hepatic enzyme increased. Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain. Psychiatric Disorders Insomnia. Respiratory, Thoracic, and Mediastinal Disorders Cough and pharyngolaryngeal pain. Vascular Disorders Hypertension. Fenofibrate Fenofibric acid is the active metabolite of fenofibrate. Adverse events reported by 2% or more of patients treated with fenofibrate and greater than placebo during double-blind, placebo-controlled trials are listed in Table 2. Adverse events led to discontinuation of treatment in 5.0% of patients treated with fenofibrate and in 3.0% treated with placebo. Increases in liver tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials. Table 2. Adverse Events Reported by 2% or More of Patients Treated with Fenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled Trials BODY SYSTEM Adverse Event Fenofibrate* (N = 439) Placebo (N = 365) BODY AS A WHOLE Abdominal Pain 4.6% 4.4% Back Pain 3.4% 2.5% Headache 3.2% 2.7% DIGESTIVE Nausea 2.3% 1.9% Constipation 2.1% 1.4% INVESTIGATIONS Abnormal Liver Tests 7.5% 1.4% Increased AST 3.4% 0.5% Increased ALT 3.0% 1.6% Increased Creatine Phosphokinase 3.0% 1.4% RESPIRATORY Respiratory Disorder 6.2% 5.5% Rhinitis 2.3% 1.1% * Dosage equivalent to 135 mg Trilipix The following adverse events have been identified during postapproval use of fenofibrate: myalgia, rhabdomyolysis, increased creatine phosphokinase, pancreatitis, increased alanine aminotransaminase, increased aspartate aminotransaminase, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, nausea, abdominal pain, anemia, headache, arthralgia, and asthenia. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a casual relationship to drug exposure.

<table ID="table_1" cellpadding="1" cellspacing="1" width="100%"> <caption>Table 1.Treatment-Emergent Adverse Events Reported in &#x2265; 3% of Patients Receiving Trilipix or Trilipix Co-Administered with a Statin During Double-Blind Controlled Studies [Number (%)]</caption> <colgroup> <col width="26%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> </colgroup> <tbody> <tr valign="top"> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Adverse Event</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Trilipix (N = 490)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Low-Dose Statin (N = 493)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Trilipix + Low-Dose Statin (N = 490)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Moderate-Dose Statin (N = 491)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Trilipix + Moderate-Dose Statin (N = 489)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">High-Dose Statin (N = 245)</content> </td> </tr> <tr> <td align="center"> <content styleCode="bold">Gastrointestinal Disorders</content> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td align="center">Constipation</td> <td align="center">16 (3.3) </td> <td align="center">11 (2.2)</td> <td align="center">16 (3.3)</td> <td align="center">13 (2.6)</td> <td align="center">15 (3.1) </td> <td align="center">6 (2.4)</td> </tr> <tr> <td align="center">Diarrhea</td> <td align="center">19 (3.9)</td> <td align="center"> 16 (3.2)</td> <td align="center"> 15 (3.1)</td> <td align="center"> 24 (4.9)</td> <td align="center"> 18 (3.7)</td> <td align="center">17 (6.9)</td> </tr> <tr> <td align="center">Dyspepsia </td> <td align="center">18 (3.7) </td> <td align="center">13 (2.6)</td> <td align="center">13 (2.7)</td> <td align="center">17 (3.5)</td> <td align="center">23 (4.7)</td> <td align="center">6 (2.4)</td> </tr> <tr> <td align="center">Nausea</td> <td align="center">21 (4.3)</td> <td align="center"> 18 (3.7)</td> <td align="center"> 17 (3.5)</td> <td align="center"> 22 (4.5)</td> <td align="center">27 (5.5)</td> <td align="center"> 10 (4.1)</td> </tr> <tr> <td align="center"> <content styleCode="bold">General Disorders and Administration Site Conditions</content> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td align="center">Fatigue</td> <td align="center">10 (2.0) </td> <td align="center">13 (2.6) </td> <td align="center">13 (2.7) </td> <td align="center">13 (2.6) </td> <td align="center">16 (3.3) </td> <td align="center">5 (2.0) </td> </tr> <tr> <td align="center">Pain</td> <td align="center">17 (3.5)</td> <td align="center">9 (1.8)</td> <td align="center">16 (3.3)</td> <td align="center">8 (1.6)</td> <td align="center">7 (1.4)</td> <td align="center">8 (3.3)</td> </tr> <tr> <td align="center"> <content styleCode="bold">Infections and Infestations</content> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td align="center"> Nasopharyngitis</td> <td align="center">17 (3.5) </td> <td align="center">29 (5.9) </td> <td align="center">23 (4.7) </td> <td align="center">16 (3.3) </td> <td align="center">21 (4.3) </td> <td align="center">9 (3.7) </td> </tr> <tr> <td align="center">Sinusitis</td> <td align="center">16 (3.3) </td> <td align="center">4 (0.8) </td> <td align="center">14 (2.9) </td> <td align="center">8 (1.6) </td> <td align="center">17 (3.5) </td> <td align="center">4 (1.6) </td> </tr> <tr> <td align="center">Upper Respiratory Tract Infection</td> <td align="center">26 (5.3)</td> <td align="center">13 (2.6)</td> <td align="center">18 (3.7)</td> <td align="center">23 (4.7)</td> <td align="center">23 (4.7)</td> <td align="center">7 (2.9)</td> </tr> <tr> <td align="center"> <content styleCode="bold">Investigations</content> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td align="center">ALT Increased</td> <td align="center">6 (1.2) </td> <td align="center">2 (0.4)</td> <td align="center">15 (3.1)</td> <td align="center">2 (0.4)</td> <td align="center">12 (2.5)</td> <td align="center">4 (1.6)</td> </tr> <tr> <td align="center"> <content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td align="center">Arthralgia</td> <td align="center">19 (3.9)</td> <td align="center">22 (4.5)</td> <td align="center">21 (4.3)</td> <td align="center">21 (4.3)</td> <td align="center">17 (3.5)</td> <td align="center">12 (4.9)</td> </tr> <tr> <td align="center">Back Pain</td> <td align="center">31 (6.3) </td> <td align="center">31 (6.3) </td> <td align="center">30 (6.1) </td> <td align="center">32 (6.5) </td> <td align="center">20 (4.1) </td> <td align="center">8 (3.3) </td> </tr> <tr> <td align="center">Muscle Spasms</td> <td align="center">8 (1.6)</td> <td align="center">18 (3.7)</td> <td align="center">12 (2.4)</td> <td align="center">24 (4.9)</td> <td align="center">15 (3.1)</td> <td align="center">6 (2.4)</td> </tr> <tr> <td align="center">Myalgia</td> <td align="center">16 (3.3) </td> <td align="center">24 (4.9) </td> <td align="center">17 (3.5) </td> <td align="center">23 (4.7) </td> <td align="center">15 (3.1) </td> <td align="center">15 (6.1) </td> </tr> <tr> <td align="center">Pain in Extremity</td> <td align="center">22 (4.5)</td> <td align="center">24 (4.9)</td> <td align="center">14 (2.9)</td> <td align="center">21 (4.3)</td> <td align="center">13 (2.7)</td> <td align="center">9 (3.7)</td> </tr> <tr> <td align="center"> <content styleCode="bold">Nervous System Disorders</content> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td align="center">Dizziness</td> <td align="center">20 (4.1)</td> <td align="center">8 (1.6)</td> <td align="center">19 (3.9)</td> <td align="center">11 (2.2)</td> <td align="center">16 (3.3)</td> <td align="center">2 (0.8)</td> </tr> <tr> <td align="center">Headache</td> <td align="center">62 (12.7)</td> <td align="center">64 (13.0)</td> <td align="center">64 (13.1)</td> <td align="center">82 (16.7)</td> <td align="center">58 (11.9)</td> <td align="center">32 (13.1)</td> </tr> <tr> <td styleCode="Toprule" colspan="7">Low-dose statin = rosuvastatin 10 mg, simvastatin 20 mg, or atorvastatin 20 mg Moderate-dose statin = rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg High-dose statin = rosuvastatin 40 mg, simvastatin 80 mg, or atorvastatin 80 mg</td> </tr> </tbody> </table>

<table ID="table_2" width="100%"> <caption>Table 2. Adverse Events Reported by 2% or More of Patients Treated with Fenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled Trials</caption> <colgroup> <col width="20%"/> <col width="27%"/> <col width="28%"/> </colgroup> <tbody> <tr> <td styleCode="Toprule Botrule"> <content styleCode="bold">BODY SYSTEM Adverse Event</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Fenofibrate* (N = 439)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">Placebo (N = 365)</content> </td> </tr> <tr> <td>BODY AS A WHOLE</td> <td> </td> <td> </td> </tr> <tr> <td> Abdominal Pain </td> <td align="center">4.6%</td> <td align="center">4.4%</td> </tr> <tr> <td> Back Pain </td> <td align="center">3.4%</td> <td align="center">2.5%</td> </tr> <tr> <td> Headache</td> <td align="center">3.2%</td> <td align="center">2.7%</td> </tr> <tr> <td>DIGESTIVE</td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td> Nausea</td> <td align="center">2.3%</td> <td align="center">1.9%</td> </tr> <tr> <td> Constipation</td> <td align="center">2.1%</td> <td align="center">1.4%</td> </tr> <tr> <td>INVESTIGATIONS</td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td> Abnormal Liver Tests</td> <td align="center">7.5%</td> <td align="center">1.4%</td> </tr> <tr> <td> Increased AST</td> <td align="center">3.4%</td> <td align="center">0.5%</td> </tr> <tr> <td> Increased ALT</td> <td align="center">3.0%</td> <td align="center">1.6%</td> </tr> <tr> <td> Increased Creatine Phosphokinase</td> <td align="center">3.0%</td> <td align="center">1.4%</td> </tr> <tr> <td>RESPIRATORY</td> <td align="center"> </td> <td align="center"> </td> </tr> <tr> <td> Respiratory Disorder</td> <td align="center">6.2%</td> <td align="center">5.5%</td> </tr> <tr> <td> Rhinitis</td> <td align="center">2.3%</td> <td align="center">1.1%</td> </tr> <tr> <td styleCode="Toprule" colspan="3">* Dosage equivalent to 135 mg Trilipix</td> </tr> </tbody> </table>