NIKP-Pitavastatin Drug Interactions

Pitavastatin is minimally metabolized by hepatic cytochrome P450 (CYP) isoenzyme 2C9 and, to a lesser extent, by CYP2C8.
Colchicine: Myopathy, including rhabdomyolysis, has been reported in patients receiving various statins concomitantly with colchicine. Caution is advised when pitavastatin is used concomitantly with colchicine.
Digoxin: Concomitant use of pitavastatin (4 mg once daily) and digoxin (0.25 mg once daily for 7 days) decreased pitavastatin peak plasma concentration by 9% increased pitavastatin area under the plasma concentration-time curve (AUC) by 4% and decreased digoxin peak plasma concentration and AUC by 4 and 3% respectively.
Enalapril: Concomitant use of pitavastatin (4 mg once daily) and enalapril (20 mg once daily for 5 days) increased AUC of pitavastatin by 6% and decreased peak plasma concentration of the drug by 7%. Peak plasma concentration and AUC of enalapril were increased by 12%.
Erythromycin: Concomitant use of pitavastatin (4 mg as a single dose on day 4) and erythromycin (500 mg 4 times daily for 6 days), pitavastatin peak plasma concentration and AUC were increased by 3.6 and 2.8 fold, respectively; such effects were considered clinically important. The interaction between pitavastatin and erythromycin probably resulted partly from erythromycin-induced inhibition of OATP1B1-mediated hepatic uptake of pitavastatin. If used concomitantly with erythromycin, dosage of pitavastatin should not exceed 1 mg once daily.
Ezetimibe: Concomitant use of pitavastatin (2 mg once daily) and ezetimibe (10 mg for 7 days) decreased pitavastatin peak plasma concentration and AUC by 0.2 and 2% respectively, and increased ezetimibe peak plasma concentration and AUC by 2 and 9% respectively.
Fibric acid derivative: Concomitant use of statin and gemfibrozil increase the risk of myopathy or rhabdomyolysis. Concomitant use of pitavastatin (4 mg once daily) and gemfibrozil (600 mg twice daily for 7 days), pitavastatin peak plasma concentration and AUC were increased by 31 and 45% respectively.
Concomitant use of statin and other fibric derivatives (e.g. fenofibrate) increases the risk of myopathy, concomitant use of pitavastatin (4 mg once daily) and fenofibrate (160 mg once daily for 7 days), pitavastatin peak plasma concentration and AUC were increased by 11 and 18% respectively. The ACC/AHA Cholesterol Management Guidelines states that the combination of fenofibrate and low or moderate intensity statin therapy may be considered only if the benefits from Atherosclerotic Cardiovascular Disease (ASCVD) risk reduction or triglyceride lowering (when triglyceride concentration exceed 500 mg/dL) outweigh the potential risk of adverse effects.
Cyclosporine: Concomitant use of pitavastatin (2 mg once daily for 6 days) and cyclosporine (2 mg/kg on day 6), pitavastatin peak plasma concentration and AUC were increased by 6.6 and 4.6 fold respectively; such effect were considered clinically important. The interaction between pitavastatin and cyclosporine probably resulted partly from cyclosporine induced inhibition of OATP1B1-mediated hepatic uptake of pitavastatin. Concomitant use of pitavastatin with cyclosporine is contraindicated.
Niacin: Concomitant use of pitavastatin and antilipidemic dosages (1 g daily or higher) of niacin increases the risk of myopathy. Data from several large randomized studies indicate that concomitant use of niacin (1.5-2 g daily) with another statin (i.e., simvastatin 40-80 mg once daily, with or without ezetimibe results in an increase in risk of severe adverse effects, including disturbance in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, infection, and bleeding.
If pitavastatin is used concomitantly with antilipidemic dosages of niacin, caution is advised and reduction in pitavastatin dosages should be considered.
Warfarin: Pitavastatin had no clinical important pharmacokinetic interaction with R- and S- warfarin. Following concomitant use of pitavastatin (4 mg once daily for 9 days) and an individualized maintenance dosage of warfarin sodium (2-7 mg for 8 days), R-warfarin peak plasma concentration and AUC increased by 3% and 7% respectively and S-warfarin peak plasma concentration and AUC increased by 3% and 6% respectively. In addition, pitavastatin (4 mg once daily) had no clinically important effect on prothrombin time (PT) and international normalized ratio (INR) in patients receiving long-term warfarin therapy; however, the manufacturer and some experts recommend close monitoring of PT and INR after pitavastatin is initiated and whether there is a change in the statin dosage in patients receiving warfarin.