Pharmacology Update
Pitavastatin Tablets (Livalo®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
The FDA has granted market approval for pitava-statin, the seventh HMG-CoA reductase inhibitor, or "statin." It is a high-potency statin similar to rosuvastatin and atorvastatin. The drug has been available in Japan since 2003 and will be marketed in the United States by Kowa Pharmaceuticals America as Livalo®.
Indications
Pitavastatin is indicated as an adjunct to diet for patients with primary hyperlipidemia and mixed dyslipidemia to reduce elevated total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein-cholesterol (HDL-C).1
Dosage
The recommended starting dose is 2 mg daily; the dose may be increased to 4 mg daily if lowering of LDL-C is inadequate. The starting dose should be reduced to 1 mg daily in patients with moderate renal impairment or end-stage renal impairment on hemodialysis. The drug may be taken without regard to meals.1
Pitavastatin is available as 1 mg, 2 mg, and 4 mg tablets.
Potential Advantages
Pitavastatin is only minimally metabolized by the cytochrome P450 isoenzyme system; therefore, drug-drug interactions involving this system are unlikely.
Potential Disadvantages
Coadministration of cyclosporine, rifampin, and erythromycin results in a clinically significant increase in the systemic exposure of pitavastatin.1 This appears to be associated with inhibition of the organic anion transporting polypeptide (OATP), resulting in reduced uptake of the drug in the liver.2 The effect of pitavastatin on cardiovascular outcomes is not known due to limited clinical experience.
Comments
Pitavastatin is a potent HMG-CoA reductase inhibitor that is chemically similar to atorvastatin and rosuva-statin. In dose ranging studies, pitavastatin at 1 mg, 2 mg, and 4 mg showed adjusted mean reduction from baseline of LDL-C of 32%, 36%, and 43%, respectively.1 In randomized, multicenter, double-blind, double-dummy, active-controlled, non-inferiority, phase 3 studies, pitavastatin 2 mg and 4 mg were similar to and non-inferior to (mean difference in reduction > 6%) atorvastatin (10 mg and 20 mg) and simvastatin (20 mg and 40 mg), respectively, in terms of LDL-C, TC, TG, and non-HDL-C reduction, as well as HDL-C elevation.1 Study participants were randomized to a 12-week study after a 6- to 8-week wash-out/dietary lead-in period. The results were the same whether patients had primary hyperlipidemia or mixed dyslipidemia with or without 2 or more risk factors for coronary disease or type 2 diabetes with combined dyslipidemia. On a mg-for-mg basis, pitavastatin is 5 times and 10 times the potency of atorvastatin and simvastatin, respectively. Pravastatin appears to be less than 1/20 the potency of pitavastatin on a mg-to-mg basis.1 Published studies of pitavastatin are primarily in Japanese patients. In patients with acute coronary syndrome (n = 252), pitavastatin 4 mg and atorvastatin 20 mg daily showed similar regression of coronary plaque volume as assessed by intravascular ultrasound.3 Pitavastatin appears to be well tolerated. The risk of skeletal muscle adverse events (myopathy and rhabdomyolysis) appears to increase in a dose-dependent manner (1.9% [1 mg], 2.8% [2 mg], and 3.1% [4 mg]) compared to 1.4% for placebo.1
Clinical Implications
Pitavastatin is the newest HMG-CoA inhibitor to be added to a crowded market. Although potent, the drug has no clear benefit over currently available statins, particularly given the lack of data regarding long- term safety and effect on cardiovascular mortality and morbidity.
References
1. Livalo Product Labeling. Montgomery, AL: Kowa Pharmaceuticals America, Inc.; July 2009.
2. Hirano M, et al. Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos 2006;34:1229-1236.
3. Hiro T, et al; JAPAN-ACS Investigators. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: A multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study). J Am Coll Cardiol 2009; 54:293-302.
The FDA has granted market approval for pitava-statin, the seventh HMG-CoA reductase inhibitor, or "statin." It is a high-potency statin similar to rosuvastatin and atorvastatin.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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