PITAVASTATIN Drug Interactions: What You Need to Know

INTERACTIONS Table 2 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when administered concomitantly with pitavastatin tablets and instructions for preventing or managing drug interactions [see Warnings and Precautions (5.1) , Clinical Pharmacology (12.3) ] .

Table

2.

Drug

Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pitavastatin Tablets Cyclosporine Clinical Impact: Cyclosporine significantly increases pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis. Intervention: Concomitant use of cyclosporine with pitavastatin tablets is contraindicated [see Contraindications (4) ] .

Gemfibrozil Clinical

Impact: Gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of gemfibrozil with statins, including pitavastatin tablets. Intervention: Avoid concomitant use of gemfibrozil with pitavastatin tablets.

Erythromycin Clinical

Impact: Erythromycin significantly increases pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis. Intervention: In patients taking erythromycin, do not exceed pitavastatin tablets 1 mg once daily [see Dosage and Administration (2.4) ] .

Rifampin Clinical

Impact: Rifampin significantly increases peak pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis. Intervention: In patients taking rifampin, do not exceed pitavastatin tablets 2 mg once daily [see Dosage and Administration (2.4) ] .

Fibrates Clinical

Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with statins, including pitavastatin tablets. Intervention: Consider if the benefit of using fibrates concomitantly with pitavastatin tablets outweighs the increased risk of myopathy and rhabdomyolysis.

Niacin Clinical

Impact: The risk of myopathy and rhabdomyolysis may be increased with concomitant use of lipid-modifying doses (≥ 1 g/day) of niacin with pitavastatin tablets. Intervention: Consider if the benefit of using lipid-modifying doses (≥ 1 g/day) of niacin concomitantly with pitavastatin tablets outweighs the increased risk of myopathy and rhabdomyolysis.

Colchicine Clinical

Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with statins, including pitavastatin tablets. Intervention: Consider the risk/benefit of concomitant use of colchicine with pitavastatin tablets. See full prescribing information for details regarding concomitant use of pitavastatin tablets with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 2.4 , 7 )

Pitavastatin tablets are contraindicated in the following conditions:

• Concomitant use of cyclosporine [see Drug Interactions (7) ] .
• Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3) ] .
• Hypersensitivity to pitavastatin or any excipients in pitavastatin tablets. Hypersensitivity reactions including angioedema, rash, pruritus, and urticaria have been reported with pitavastatin tablets [see Adverse Reactions (6) ] .
• Cyclosporine ( 4 , 7 )
• Active liver failure or decompensated cirrhosis ( 4 , 5.3 )
• Hypersensitivity to pitavastatin or any excipients in pitavastatin tablets ( 4 )

AND PRECAUTIONS

• Myopathy and Rhabdomyolysis: Risk factors include age 65 or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher pitavastatin tablets dosage. Discontinue pitavastatin tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue pitavastatin tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the pitavastatin tablets dosage. Instruct patients to promptly report unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever. ( 5.1 , 7 , 8.5 , 8.6 )
• Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue pitavastatin tablets if IMNM is suspected. ( 5.2 )
• Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pitavastatin tablets. ( 5.3 )

5.1 Myopathy and Rhabdomyolysis Pitavastatin tablets may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including pitavastatin tablets.

Risk

Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use of certain drugs (including other lipid-lowering therapies), and higher pitavastatin tablets dosage [see Dosage and Administration (2.2) , Drug Interactions (7) , and Use in Specific Populations (8.5 , 8.6) ] . Dosages of pitavastatin tablets greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. The maximum recommended dose of pitavastatin tablets is 4 mg once daily. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis Pitavastatin tablets are contraindicated in patients taking cyclosporine and not recommended in patients taking gemfibrozil [see Contraindications (4) and Drug Interactions (7) ] . There are pitavastatin tablets dosage restrictions for patients taking erythromycin or rifampin [see Dosage and Administration (2.4) ] . The following drugs when used concomitantly with pitavastatin tablets may also increase the risk of myopathy and rhabdomyolysis: lipid-modifying dosages of niacin (> 1 grams/day), fibrates, and colchicine [see Drug Interactions (7) ] . Discontinue pitavastatin tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if pitavastatin tablets are discontinued. Temporarily discontinue pitavastatin 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 pitavastatin 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, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that 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. Discontinue pitavastatin tablets if IMNM is suspected.

5.3 Hepatic Dysfunction Increases in serum transaminases have been reported with pitavastatin tablets <span class="opacity-50 text-xs">[see Adverse Reactions (6) ]</span> . In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin tablets. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Consider liver enzyme testing before the initiation of pitavastatin tablets and when clinically indicated thereafter. Pitavastatin tablets are contraindicated in patients with acute liver failure or decompensated cirrhosis <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pitavastatin tablets.

5.4 Increases in HbA1c and Fasting Serum Glucose Levels Increases in HbA1c and fasting serum glucose levels have been reported with statins, including pitavastatin tablets. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.