Manufacturer:

Kowa and Lilly

Pharmacological Class:

HMG-CoA reductase inhibitor

Active Ingredient(s):

Pitavastatin 1mg, 2mg, 4mg; tabs.

Indication(s):

Adjunct to diet: To reduce elevated total-C, LDL-C, ApoB, and TG, and to increase HDL-C in primary hyperlipidemia and mixed dyslipidemia.

Pharmacology:

Pitavastatin competitively inhibits HMG-CoA reductase, an enzyme that controls the rate of endogenous cholesterol synthesis. This results in the hepatic uptake of LDL from the blood and a decrease in plasma total cholesterol. Also, the inhibition of cholesterol biosynthesis reduces the levels of very low density lipoproteins (VLDL).

Clinical Trials:

A dose-ranging study compared the ef­fi­ca­cy of pitavastatin (1, 2, and 4mg per day) to placebo in 251 patients with primary hyperlipidemia. At 12 weeks, pitavastatin significantly reduced plasma LDL-C, TC, TG and ApoB compared to placebo. Increases in HDL-C were variable across the dosage range.

Pitavastatin was compared to atorvastatin in a study involving 817 patients with primary hyperlip­id­emia or mixed dyslipidemia over 12 weeks. Pitavastatin 2mg and 4mg was non-inferior to atorvastatin 10mg and 20mg, respectively, for mean percent change in LDL-C.

Pitavastatin was compared to simvastatin in 843 patients with primary hyperlipidemia or mixed dyslip­idemia over 12 weeks. Pitavastatin 2mg and 4mg was non-inferior to simvastatin 20mg and 40mg, respectively, for mean percent change in LDL-C.

In a 12-week parallel-group study, pitavastatin was compared to pravastatin in 942 elderly patients with primary hyperlipidemia or mixed dyslipidemia. Pitavastatin 1, 2, and 4mg/day significantly reduced LDL-C compared to pravastatin 10, 20, and 40mg/day, respectively.

In a 12-week study involving 351 patients with ≥2 risk factors for coronary heart disease and primary hyperlipidemia or mixed dyslipidemia, pitavastatin 4mg was shown to be non-inferior to simvastatin 40mg for mean percent change in LDL-C.

Pitavastatin 4mg was compared to atorvastatin 20mg in a study involving 410 patients with type 2 diabetes and combined dyslipidemia. The two treatment groups were not statistically different regarding LDL-C, but non-inferiority was not established for pitavastatin.

Legal Classification:

Rx

Adults:

Initially 2mg once daily; may increase after 4 weeks to max 4mg once daily. Moderate renal impairment (CrCl 30 to <60mL/min, or ESRD with hemodialysis): 1mg once daily; max 2mg once daily. Concomitant erythromycin: max 1mg daily. Concomitant rifampin: max 2mg daily.

Children:

Not recommended.

Contraindication(s):

Active liver disease. Unexplained, persistent elevated serum transaminases. Severe renal impairment (CrCl <30mL/min without dialysis). Concomitant cyclosporine or lopinavir/ritonavir. Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions:

Risk factors for myopathy (eg, renal impairment, inadequately treated hypothyroidism, age >65 years, concomitant fibrates, lipid-modifying niacin). Monitor liver function (before therapy, at 12 weeks after starting or dose increase, then periodically): reduce dose or discontinue if serum transam­inase levels ≥3xULN persist. Substantial alcohol ingestion. Discontinue if myopathy or markedly elevated CK levels occur; suspend if a predisposition to development of renal failure secondary to rhabdomyolysis develops (eg, sepsis, hypotension, dehydration, trauma, seizures; severe endocrine, metabolic, or electrolyte disorders).

Interaction(s):

Potentiated by cyclosporine, possibly lopinavir/ritonavir (see Contraindications). Fibrates, niacin increase myopathy risk (consider reducing pitavastatin dose). Potentiated by erythromycin, rifampin (see Adult dose). Monitor warfarin.

Adverse Reaction(s):

Myalgia, back/extremity pain, GI upset, constipation, elevated creatine phosphoki­nase, transaminases, alkaline phosphatase, bilirubin, glucose; myopathy, rhabdomyolysis with renal dysfunction, hypersensitivity reactions.

How Supplied:

Tabs—90

Last Updated:

6/24/2010