The following serious adverse reactions are discussed in greater detail in other sections of the label: Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see Warnings and Precautions (5.1)]. Liver Enzyme Abnormalities [see Warning and Precautions (5.2)]. Of 4,798 patients enrolled in 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 patients were administered pitavastatin 1 mg to 4 mg daily. The mean continuous exposure of pitavastatin (1 mg to 4 mg) was 36.7 weeks (median 51.1 weeks). The mean age of the patients was 60.9 years (range; 18 years – 89 years) and the gender distribution was 48% males and 52% females. Approximately 93% of the patients were Caucasian, 7% were Asian/Indian, 0.2% were African American and 0.3% were Hispanic and other. The most frequent adverse reactions (rate ≥2.0% in at least one marketed dose) were myalgia, back pain, diarrhea, constipation and pain in extremity. (6) To report SUSPECTED ADVERSE REACTIONS, contact Kowa Pharmaceuticals America, Inc. at 1-877-334-3464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies on LIVALO are conducted in varying study populations and study designs, the frequency of adverse reactions observed in the clinical studies of LIVALO cannot be directly compared with that in the clinical studies of other HMG-CoA reductase inhibitors and may not reflect the frequency of adverse reactions observed in clinical practice. Adverse reactions reported in ≥ 2% of patients in controlled clinical studies and at a rate greater than or equal to placebo are shown in Table 1. These studies had treatment duration of up to 12 weeks. Table 1. Adverse Reactions* Reported by ≥2.0% of Patients Treated with LIVALO and > Placebo in Short-Term Controlled Studies * Adverse reactions by MedDRA preferred term. Adverse Reactions* Placebo N= 208 LIVALO 1 mg N=309 LIVALO 2 mg N=951 LIVALO 4 mg N=1540 Back Pain 2.9% 3.9% 1.8% 1.4% Constipation 1.9% 3.6% 1.5% 2.2% Diarrhea 1.9% 2.6% 1.5% 1.9% Myalgia 1.4% 1.9% 2.8% 3.1% Pain in extremity 1.9% 2.3% 0.6% 0.9% Other adverse reactions reported from clinical studies were arthralgia, headache, influenza, and nasopharyngitis. The following laboratory abnormalities have also been reported: elevated creatine phosphokinase, transaminases, alkaline phosphatase, bilirubin, and glucose. In controlled clinical studies and their open-label extensions, 3.9% (1 mg), 3.3% (2 mg), and 3.7% (4 mg) of pitavastatin-treated patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: elevated creatine phosphokinase (0.6% on 4 mg) and myalgia (0.5% on 4 mg). Hypersensitivity reactions including rash, pruritus, and urticaria have been reported with LIVALO. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of LIVALO. 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 LIVALO therapy reported since market introduction, regardless of causality assessment, include the following: abdominal discomfort, abdominal pain, dyspepsia, nausea, asthenia, fatigue, malaise, hepatitis, jaundice, fatal and non-fatal hepatic failure, dizziness, hypoesthesia, insomnia, depression, interstitial lung disease, erectile dysfunction and muscle spasms. 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). There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1)].