warnings and cautions
5 WARNINGS AND PRECAUTIONS Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase in a dose-dependent manner, with advanced age (≥65), renal impairment, and inadequately treated hypothyroidism. Advise patients to promptly report unexplained and/or persistent muscle pain, tenderness, or weakness, and discontinue pitavastatin tablets ( 5.1 ) Liver enzyme abnormalities : Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter ( 5.2 ) 5.1 Skeletal Muscle Effects Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Pitavastatin Tablets. These risks can occur at any dose level, but increase in a dose-dependent manner. Pitavastatin tablets should be prescribed with caution in patients with predisposing factors for myopathy. These factors include advanced age (≥65 years), renal impairment, and inadequately treated hypothyroidism. The risk of myopathy may also be increased with concurrent administration of fibrates or lipid-modifying doses of niacin. Pitavastatin tablets should be administered with caution in patients with impaired renal function, in elderly patients, or when used concomitantly with fibrates or lipid-modifying doses of niacin [see Drug Interactions ( 7.6 ), Use in Specific Populations ( 8.5 , 8.6 ) and Clinical Pharmacology ( 12.3 )]. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should be exercised when prescribing pitavastatin tablets with colchicine [see Drug Interactions ( 7.7 ]. 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; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents. Pitavastatin tablets therapy should be discontinued if markedly elevated creatine kinase (CK) levels occur or myopathy is diagnosed or suspected. Pitavastatin tablets therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures). All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing pitavastatin tablets. 5.2 Liver Enzyme Abnormalities Increases in serum transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase, or alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase) have been reported with HMG-CoA reductase inhibitors, including pitavastatin tablets. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. In placebo-controlled Phase 2 studies, ALT >3 times the upper limit of normal was not observed in the placebo, pitavastatin tablets 1 mg, or pitavastatin tablets 2 mg groups. One out of 202 patients (0.5%) administered pitavastatin tablets 4 mg had ALT >3 times the upper limit of normal. It is recommended that liver enzyme tests be performed before the initiation of pitavastatin tablets and if signs or symptoms of liver injury occur. All patients treated with pitavastatin tablets should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with pitavastatin tablets, promptly interrupt therapy. If an alternate etiology is not found do not restart pitavastatin tablets. As with other HMG-CoA reductase inhibitors, pitavastatin tablets should be used with caution in patients who consume substantial quantities of alcohol. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of pitavastatin tablets [see Contraindications ( 4 )]. 5.3 Endocrine Function Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including pitavastatin tablets.