Fda.gov 08/03/2009
INTRODUCTION 11.5 years of life are lost- consequence of MI. Hyperlipidemia -atherosclerosis & associated     condition li...
INTRODUCTIONNCMH- GOI- 62 million by 2015an inhibitor of HMG-CoA reductase.synthetic lipid-lowering agent for oraladminist...
Classification of Plasma Lipid LevelsTotal cholesterol              <200 mg/dl Desirable                200-239 mg/dl Bord...
CHEMISTRYChemical name:               (3R,5S,6E)-7-[2-cyclopropyl-4- (4-   fluorophenyl) quinolin-3-yl]-3,5-dihydroxyhept ...
PHARMACOKINETIC Bioavailability : 60% TMAX : 1 hour Volume of distribution : 148 L Half life : 11 hours Plasma protein bin...
MECHANISM OF ACTIONCompetitive inhibitor of HMG-CoA reductase, whichis rate limiting enzyme in cholesterol synthesis inliv...
DOSAGE AND ADMINISTRATION Can be taken with or without food, at any time of day Dose Range: 1 mg to 4 mg OD. Primary hyper...
CONTRAINDICATIONS1) Known hypersensitivity2) Active liver disease3) Pregnancy and nursing mother4) Co-administration with ...
DRUG INTERACTIONSCyclosporine : C/ILopinavir/Ritonavir: combinationshould not be usedErythromycin : limit dose to 1 mgRifa...
WARNING PRECAUTIONS Skeletal muscle effects ( e.g., myopathy and rhabdomyolysis) : risk increases in dose dependent manner...
USE IN SPECIFIC POPULATIONSPregnancy :          Teratogenic effects: Pregnancy Category XNursing Mothers :          Rat st...
CLINICAL STUDIES Active controlled study with atorvastatin (NK -104-301) For the percent change from baseline to endpoint ...
CLINICAL STUDY Dose-ranging study: to evaluate the efficacy of Livalo compared with placebo Dose-Response in Patients wi...
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Pitavastatin
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Pitavastatin

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  • Severe hypertriglyceridemia (i.e., triglyceride levels of &gt;1000 mg/dl) requires therapy to prevent pancreatitis. Moderately elevated triglyceride levels (150 to 400 mg/dl) also are of concern because they often occur as part of the metabolic syndrome, which includes insulin resistance, obesity, hypertension, low HDL-C levels, and substantially increased CHD risk. The atherogenic dyslipidemia in patients with the metabolic syndrome is characterized by moderately elevated triglycerides, low HDL-C levels, and lipid-depleted LDL (sometimes referred to as &quot;small, dense LDL&quot;) (Reaven, 2002; Reaven, 2003; Grundy et al., 2004a; Grundy et al., 2004c). The metabolic syndrome affects ~25% of adults and is common in CHD patients; hence, identification of moderate hypertriglyceridemia in a patient, even if the total cholesterol level is normal, should trigger an evaluation to identify this disorder
  • Table 35–1. National Cholesterol Education Program: Adult Treatment Guidelines (2001).Desirable Borderline to High1HighTotal cholesterol &lt; 200 (5.2)2200–2392 (5.2–6.2)&gt; 240 (6.2)2LDL cholesterol &lt; 130 (3.4)3130–159 (3.4–4.1) &gt; 160 (4.1)HDL cholesterol &gt; 60 (1.55)Men &gt; 40 (1.04)Women &gt; 50 (1.30)Triglycerides &lt; 150 (1.7) 150–199 (1.7–2.3) &gt; 200 (2.3)1 Consider as high if coronary disease or more than 2 risk factors are present2 mg/dL (mmol/L)3 Optimal level is &lt; 100 (2.6)
  • , When lowering of LDL-C is insufficient, the dosage may be increased to a (GFR 30 -60mL/min/1.73 m2)
  • , inadequately treated hypothyroidism
  • have shown that pitavastatin isOf the 2,800 patients randomized to LIVALO 1 mg to 4 mg in controlled clinical studies, 1,209 (43%) were 65 years and older.
  • Treatment Based on LDL-C Levels (2004 Revision of NCEP Adult Treatment Panel III Guidelines)RISK CATEGORY LDL-C GOAL THERAPEUTIC LIFESTYLE CHANGE DRUG THERAPY Very high risk &lt;70 mg/dl* No threshold No threshold Atherosclerosis-induced CHD plus one of: (a) multiple risk factors,(b) diabetes mellitus, (c) a poorly controlled single factor,(d) acute coronary syndrome,(e) metabolic syndrome       High risk &lt;100 mg/dl* No threshold No threshold CHD or CHD equivalent       Moderately high risk &lt;130 mg/dl (Optional &lt;100 mg/dl) ≥100 mg/dl ≥130 mg/dl (100-129 mg/dl)a 2+ risk factors       10-year risk: 10%-20%       Moderate risk &lt;130 mg/dl ≥130 mg/dl &gt;160 mg/dl 2+ risk factors       10-year risk &lt;10%       0-1 risk factor &lt;160 mg/dl ≥160 mg/dl ≥190 mg/dl (Optional: 160-189 mg/dl)b
  • Pitavastatin

    1. 1. Fda.gov 08/03/2009
    2. 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. 3. INTRODUCTIONNCMH- GOI- 62 million by 2015an inhibitor of HMG-CoA reductase.synthetic lipid-lowering agent for oraladministration.Hygroscopic and slightly unstable in light.comparative safety profile, fewer drug interactions.Effective in elderly, diabetic & those at high risk ofdeveloping CHD.
    4. 4. Classification of Plasma Lipid LevelsTotal 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 HighLDL-C <70 mg/dl Optimal for very high risk (minimal goal for CHDequivalent 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 highTriglycerides <150 mg/dl Normal 150-199 mg/dl Borderline high 200-499 mg/dl High ≥500 mg/dl Very high
    5. 5. CHEMISTRYChemical name: (3R,5S,6E)-7-[2-cyclopropyl-4- (4- fluorophenyl) quinolin-3-yl]-3,5-dihydroxyhept -6-enoic acidChemical structure:Molecular formula: C25H24FNO4Molecular weight: 421.461
    6. 6. 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
    7. 7. MECHANISM OF ACTIONCompetitive inhibitor of HMG-CoA reductase, whichis rate limiting enzyme in cholesterol synthesis inliver. INDICATION & USESPrimary hyperlipidemia and mixed dyslipidemia as an adjuvant therapy to diet to reduce elevated TC, LDL-C,TG and to increase HDL-C.
    8. 8. 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.
    9. 9. CONTRAINDICATIONS1) Known hypersensitivity2) Active liver disease3) Pregnancy and nursing mother4) Co-administration with cyclosporineADVERSE DRUG REACTIONS Most common: myalgia, back pain, diarrhea, constipation and pain in extrimity . Most serious: rhabdomyolysis , myopathy , myoglobinuria and ARF.
    10. 10. DRUG INTERACTIONSCyclosporine : C/ILopinavir/Ritonavir: combinationshould not be usedErythromycin : limit dose to 1 mgRifampin : limit dose to 2 mgFibrates : increased risk of skeletalmuscles effectsNiacin : increased risk of skeletalmuscles effects
    11. 11. 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
    12. 12. USE IN SPECIFIC POPULATIONSPregnancy : Teratogenic effects: Pregnancy Category XNursing 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.
    13. 13. 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)
    14. 14. 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
    15. 15. THANK YOU
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