Pitavastatin is currently FDA approved for the management of primary dyslipidemia and mixed dyslipidemia as adjunctive therapy to dietary changes to help lower total cholesterol, low-density lipoprotein cholesterol (LDL), apolipoprotein B (Apo B), triglycerides (TG) and to increase high-density lipoprotein cholesterol (HDL).[1][2][3] It is also FDA approved to treat heterozygous familial hypercholesterolemia (HeFH) in pediatric patients over 8 years of age.[4][5] Unlike other statins, pitavastatin has not been studied in any large randomized controlled study to determine whether its use is associated with decreased cardiovascular events.

Pitavastatin competitively inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway. Inhibiting this enzyme decreases the production of mevalonic acid from HMG-CoA. This enzymatic inhibition, in turn, increases the number of LDL receptors expressed on hepatocytes to compensate for the loss of mevalonic acid and results in greater LDL catabolism.[6][7]

Pharmacokinetics: 

Absorption: 

Peak plasma concentrations of pitavastatin are reached within approximately 1 hour after oral administration. It has a bioavailability greater than 60%. It has some absorption in the colon; however, its absorption mainly occurs in the small intestine. In comparison to all other statins, pitavastatin reaches peak plasma concentrations the fastest and has the highest bioavailability.

Distribution: 

Pitavastatin is largely bound to protein (>99%), primarily to albumin and alpha-1 acid glycoprotein, with a mean volume of distribution of 148L. 

Metabolism: 

Pitavastatin is mainly metabolized in the liver by UGT1A3 and UGT2B7 and minimally by CYP2C9 and CYP2C8.

Excretion: 

The half-life of pitavastatin is approximately 12 hours. The majority of pitavastatin (79%) is excreted in the feces, whereas approximately 15% is excreted in the urine.[6]

Pitavastatin is available as 1 mg, 2 mg, and 4 mg tablets for oral administration. Patients may take the drug at any time of the day; however, the time of day should remain consistent. Patients can take it with or without food. 

Adult dosing: 

Pitavastatin is a moderate-intensity statin. The dose range for pitavastatin is between 1 mg to 4 mg once daily; 2 mg once daily is the recommended starting dosage, and the maximum dose is 4 mg once daily. The actual starting dosage and maintenance dosage should be individualized to the patient's characteristics and goals of therapy as per the American College of Cardiology/American Heart Association Guidelines.[1][8] Lipid levels should be assessed four weeks after starting therapy to determine whether the response is appropriate and whether the dosage is appropriate.  

Pediatric dosing: 

For children aged eight years and older, for management of HeFH, 2 mg once daily is the recommended starting dosage. Lipid levels should be re-assessed four weeks after initiating therapy and adjusted accordingly. The maximum recommended dosage is 4 mg once daily.[4][5]

Geriatric Dosing: 

Research has determined no significant difference in terms of safety and efficacy was determined between geriatric patients (age greater than 65) and younger patients.[7][9]

Renal impairment:

Patients with a glomerular filtration rate between 15 to 59 mL/min/1.73 m not requiring hemodialysis and patients with end-stage renal disease requiring hemodialysis should initiate pitavastatin at 1 mg once daily to a maximum dose of 2 mg once daily. 

Hepatic impairment:

Pitavastatin is contraindicated in the presence of active liver disease and patients with unexplained elevated liver enzymes.[9][10]

Drug Interactions: 

Pitavastatin is mainly metabolized by glucuronidation via liver UGTs, and there is comparably only minimal metabolism by cytochrome P450 enzymes.[6]

The following drugs may decrease the serum concentration of pitavastatin: darunavir/ritonavir, lopinavir/ritonavir, ezetimibe, digoxin, and itraconazole. 

The following drugs may increase the serum concentration of pitavastatin: cyclosporine, erythromycin, rifampin, atazanavir, gemfibrozil, fenofibrate, enalapril, and diltiazem.[7]

The most commonly reported adverse effects related to pitavastatin use include back pain, constipation, diarrhea, myalgia, and pain in extremities. Reports exist of rash, pruritus, and urticaria. There are also reports of myopathy and rhabdomyolysis, leading to acute renal failure. Pitavastatin use can also cause lab abnormalities, including elevated creatine phosphokinase, transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase, or alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase), alkaline phosphatase, bilirubin, and glucose. High fasting serum glucose levels and high HgA1c levels have also occurred with pitavastatin use.[10][11][12]

Pitavastatin use is contraindicated in patients with known hypersensitivity, including rash, pruritus, urticaria, to any component of this drug. Its use is also contraindicated in patients with active liver disease or unexplained elevated levels of hepatic transaminases. Pregnant women or ones who may become pregnant should also avoid pitavastatin use. As pitavastatin is known to pass into breast milk, the recommendation is that nursing mothers also avoid pitavastatin use.[10][13]