LIVALO® (pitavastatin) Tablet

LIVALO (pitavastatin) Tablet, Film Coated for Oral use
Initial U.S. Approval: 2009

DESCRIPTION
LIVALO (pitavastatin) is an inhibitor of HMG-CoA reductase. It is a synthetic lipid-lowering agent for oral administration.

The chemical name for pitavastatin is (+)monocalcium bis{(3R, 5S, 6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate}.

Pitavastatin is odorless and occurs as white to pale-yellow powder. It is freely soluble in pyridine, chloroform, dilute hydrochloric acid, and tetrahydrofuran, soluble in ethylene glycol, sparingly soluble in octanol, slightly soluble in methanol, very slightly soluble in water or ethanol, and practically insoluble in acetonitrile or diethyl ether. Pitavastatin is hygroscopic and slightly unstable in light.

Each film-coated tablet of LIVALO contains 1.045 mg, 2.09 mg, or 4.18 mg of pitavastatin calcium, which is equivalent to 1 mg, 2 mg, or 4 mg, respectively of free base and the following inactive ingredients: lactose monohydrate, low substituted hydroxypropylcellulose, hypromellose, magnesium aluminometasilicate, magnesium stearate, and film coating containing the following inactive ingredients: hypromellose, titanium dioxide, triethyl citrate, and colloidal anhydrous silica.

Pharmacodynamics
In a randomized, double-blind, placebo-controlled, 4-way parallel, active-comparator study with moxifloxacin in 174 healthy participants, LIVALO was not associated with clinically meaningful prolongation of the QTc interval or heart rate at daily doses up to 16 mg (4 times the recommended maximum daily dose).

LIVALO is a HMG-CoA reductase inhibitor indicated for:

Patients with primary hyperlipidemia and mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C)

--Known hypersensitivity to product components
--Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels
--Women who are pregnant or may become pregnant
--Nursing mothers
--Co-administration with cyclosporine

--Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase in a dose-dependent manner, with advanced age (>65), renal impairment, inadequately treated hypothyroidism, and combination use with fibrates. Advise patients to promptly report unexplained muscle pain, tenderness, or weakness, and discontinue LIVALO if signs or symptoms appear.

--Liver enzymes abnormalities and monitoring: Persistent elevations in hepatic transaminases can occur. Monitor liver enzymes before and during treatment.

DRUG INTERACTIONS

--Erythromycin: Combination increases pitavastatin exposure. Limit LIVALO to 1 mg once daily -
--Rifampin: Combination increases pitavastatin exposure. Limit LIVALO to 2 mg once daily -
--Fibrates: Use with fibrate products may increase the risk of adverse skeletal muscle effects-

USE IN SPECIFIC POPULATIONS

--Pediatric use: Safety and effectiveness have not been established.
--Renal impairment: Limitation of a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily for patients with moderate and severe renal impairment as well as patients receiving hemodialysis

To report SUSPECTED ADVERSE REACTIONS, contact Kowa Pharmaceuticals America, Inc. at 1-877-334-3464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

After initiation or upon titration of LIVALO, lipid levels should be analyzed after 4 weeks and the dosage adjusted accordingly.

Dosage in Patients with Renal Impairment:
Patients with moderate and severe renal impairment (glomerular filtration rate 30 – 59 mL/min/1.73 m2 and 15 – 29 mL/min/1.73 m2 not receiving hemodialysis, respectively) as well as end-stage renal disease receiving hemodialysis should receive a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily.

Use with Erythromycin:
In patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded.

Use with Rifampin:
In patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded

Tablets: 1 mg, 2 mg, and 4 mg

Manufactured under license from: Kowa Company, Limited Tokyo 103-8433 Japan
Product of Japan
Manufactured into tablets by: Patheon, Inc. Cincinnati, OH 45237 USA
Marketed by: Kowa Pharmaceuticals America, Inc. Montgomery, AL 36117 USA
and Lilly USA, LLC. Indianapolis, IN 46285 USA

Revised: 08/2011