This document summarizes information about the drug Livalo (pitavastatin), including its indications, mechanism of action, pharmacokinetics, dosage and administration, drug interactions, warnings, and clinical trial results. Livalo is a statin approved to reduce cholesterol levels and treat hyperlipidemia. It works by inhibiting the HMG-CoA reductase enzyme in the liver to decrease cholesterol synthesis. Clinical trials demonstrated Livalo to be effective at reducing LDL-C, total cholesterol, and triglycerides and increasing HDL-C compared to other statins like atorvastatin, simvastatin, and pravastatin.

1. Fda.gov 08/03/2009

2. INTRODUCTION
11.5 years of life are lost- consequence of MI.
Hyperlipidemia -atherosclerosis & associated
condition like CAD CerebroVD PAD.
Dyslipidemia -endothelial damage – HT.
Fatal & nonfatel CHD events & strokes – reduced by
30-40%- statin.
Higher cholesterol – higher CHD risk.
NCEP-ATP3 – new target LDL-C <70mg/dl-high risk
patient.

3. INTRODUCTION
NCMH- GOI- 62 million by 2015
an inhibitor of HMG-CoA reductase.
synthetic lipid-lowering agent for oral
administration.
Hygroscopic and slightly unstable in light.
comparative safety profile, fewer drug interactions.
Effective in elderly, diabetic & those at high risk of
developing CHD.

4. Classification of Plasma Lipid Levels
Total cholesterol
<200 mg/dl Desirable
200-239 mg/dl Borderline high
≥240 mg/dl High
HDL-C
<40 mg/dl Low (consider <50 mg/dl as low for women)
>60 mg/dl High
LDL-C
<70 mg/dl Optimal for very high risk (minimal goal for CHD
equivalent patients)
<100 mg/dl Optimal
100-129 mg/dl Near optimal
130-159 mg/dl Borderline high
160-189 mg/dl High
≥190 mg/dl Very high
Triglycerides
<150 mg/dl Normal
150-199 mg/dl Borderline high
200-499 mg/dl High
≥500 mg/dl Very high

6. CHEMISTRY
Chemical name:
(3R,5S,6E)-7-[2-cyclopropyl-4- (4-
fluorophenyl) quinolin-3-yl]-3,5-dihydroxyhept
-6-enoic acid
Chemical structure:
Molecular formula: C25H24FNO4
Molecular weight: 421.461

7. PHARMACOKINETIC
Bioavailability : 60%
TMAX : 1 hour
Volume of distribution : 148 L
Half life : 11 hours
Plasma protein binding : 96%
Metabolism : hepatic (substrate of CYP2C9)
Excretion : biliary

8. MECHANISM OF ACTION
Competitive inhibitor of HMG-CoA reductase, which
is rate limiting enzyme in cholesterol synthesis in
liver.
INDICATION & USES
Primary hyperlipidemia and mixed dyslipidemia as
an adjuvant therapy to diet to reduce elevated
TC, LDL-C,TG and to increase HDL-C.

9. DOSAGE AND ADMINISTRATION
Can be taken with or without food, at any time of day
Dose Range: 1 mg to 4 mg OD.
Primary hyperlipidemia and mixed dyslipidemia:
Starting dose 2 mg, maximum of 4 mg/day
Moderate renal impairment and ESRD on haemodialysis:
Starting dose 1mg OD max. dose of 2mg/day
Dosage Forms And Strengths:
tab. 1 mg , 2 mg and 4 mg.

10. CONTRAINDICATIONS
1) Known hypersensitivity
2) Active liver disease
3) Pregnancy and nursing mother
4) Co-administration with cyclosporine
ADVERSE DRUG REACTIONS
Most common:
myalgia, back pain, diarrhea, constipation and
pain in extrimity .
Most serious:
rhabdomyolysis , myopathy , myoglobinuria and
ARF.

11. DRUG INTERACTIONS
Cyclosporine : C/I
Lopinavir/Ritonavir: combination
should not be used
Erythromycin : limit dose to 1 mg
Rifampin : limit dose to 2 mg
Fibrates : increased risk of skeletal
muscles effects
Niacin : increased risk of skeletal
muscles effects

12. WARNING PRECAUTIONS
Skeletal muscle effects ( e.g., myopathy and
rhabdomyolysis) : risk increases in dose dependent
manner, with advance age, renal impairment and
combination use with fibrates.
Liver enzymes abnormalities and monitoring:
persistent elevation in AST/ALT can occur. (>3
times upper limit of normal-decrease dose/
withdraws

13. USE IN SPECIFIC POPULATIONS
Pregnancy :
Teratogenic effects: Pregnancy Category X
Nursing Mothers :
Rat study-excreted into breast milk.
Pediatric Use:
Safety and have not been established.
Geriatric Use:
No significant differences in efficacy or safety
were observed between elderly & younger patients.

14. CLINICAL STUDIES
Active controlled study with atorvastatin (NK -104-301)
For the percent change from baseline to endpoint in LDL-C, LIVALO was
Superior to atorvastatin. for the two pair wise comparisons: LIVALO 2 mg
vs. atorvastatin 10 mg and LIVALO 4 mg vs. atorvastatin 20 mg. Mean
treatment differences (95% CI) were 1% (-1%, 3%) and 1% (-
2%,4%), respectively.
Active-controlled study with simvastatin (NK-104-302):
Active-controlled study with pravastatin in elderly (NK-104-306):
Active-controlled study with simvastatin in patients with ≥ 2 risk
factors for coronary heart disease (NK-104-304)
Active-controlled study with atorvastatin in patients with type II
diabetes mellitus (NK-104-305)

15. CLINICAL STUDY
 Dose-ranging study: to evaluate the efficacy of Livalo compared with placebo
 Dose-Response in Patients with Primary Hypercholesterolemia (Adjusted
Mean % Change from Baseline at Week 12)
Treatme- N LDL-C TC TG Apo -B HDL-C
nt
PLACEBO 53 -3 -2 1 -2 0
Livalo 1 52 -32 -23 -15 -25 8
mg
Livalo 2 49 -36 -26 -19 -30 7
mg
Livalo 4 51 -43 -31 -18 -35 5
mg

16. THANK YOU