You know every patient is unique. You know one statin won’t fit all. DO YOU KNOW THE LIVALO® DIFFERENCE?

HELP YOUR PATIENTS SAVE WITH THE LIVALO SAVINGS CARD*

Eligible patients
may pay as little as $18 per month.>
*Certain rules and restrictions apply.

METABOLISM

HELP PATIENTS AVOID CERTAIN 
DRUG INTERACTIONS

CYP450: A CONGESTED METABOLIC PATHWAY

ZOOM CYP450 Pathway
  • LIVALO is only minimally metabolized through the CYP450 system6
    • The principal route of LIVALO metabolism is conjugation with glucuronic acid via liver UGTs with subsequent formation of pitavastatin lactone
  • Based on its metabolism, LIVALO may have reduced potential for clinically significant drug 
 interactions mediated by the CYP450 system6-8
  • No dose adjustment for a number of classes of drugs including CCBs, the anticoagulant warfarin, as well as those patients of Asian descent6
UGT=uridine 5'-diphosphate (UDP) glucuronosyltransferase.
Drug Interactions
  • Cyclosporine. Co-administration is contraindicated
  • Erythromycin. Do not exceed a 1-mg dose of LIVALO once daily
  • Rifampin. Do not exceed a 2-mg dose of LIVALO once daily
  • Use with gemfibrozil should be avoided
  • Other fibrates. Co-administration with fenofibrate did not result in a significant increase in AUC or Cmax§ of LIVALO, however, HMG-CoA reductase inhibitors like LIVALO should be used with caution with fibrates due to the increased risk of myopathy
  • Niacin (≥1 g/day). A reduction in LIVALO dosage should be considered due to potential risk of skeletal muscle effects
  • Colchicine. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should be exercised when prescribing LIVALO with colchicine
AUC = area under the curve.
§Cmax = maximum concentration observed.
  • References:
  • 1. Atorvastatin (Lipitor) [prescribing information], New York, NY, Pfizer, Inc. 2012.
  • 2. Simvastatin (Zocor) [prescribing information], Whitehouse Station, NJ, Merck & Co., Inc. 2012.
  • 3. Statin Market TRx by Year. Symphony Health Solutions; January 2015. DOF 1152015.
  • 4. Guengerich FP. Cytochrome P450 and chemical toxicology. Chem Res Toxicol. 2008;21(1):70-83.
  • 5. Huang SM, Temple R, Throckmorton DC, Lesko LJ. Drug interaction studies: study design, data analysis, and implications for dosing and labeling. Clin Pharmacol Ther. 2007;81(2):298-304.
  • 6. LIVALO [prescribing information]. Montgomery, AL: Kowa Pharmaceuticals America, Inc; October 2013.
  • 7. Neuvonen PJ. Drug interactions with HMG-CoA reductase inhibitors (statins): the importance of CYP enzymes, transporters and pharmacogenetics. Curr Opin Investig Drugs. 2010;11(3):323-332.
  • 8. Corsini A, Ceska R. Drug-drug interactions with statins: will pitavastatin overcome the statins’ Achilles’ heel? Curr Med Res Opin. 2011;27(8):1551-1562.
METABOLISM↑

THE REALITY OF POLY-PHARMACY

MANAGING MULTIPLE MEDICATIONS CAN BE CHALLENGING

In the largest survey of statin users ever conducted in the United States, there were 10,138 respondants, 1,220 of which were former statin users, and 8,918 were current users.1

  • Drug interaction potential
    8 out of 101
    • 84% (> 8 in 10) of all respondents used at least one prescription, OTC, or herbal/ vitamin product, which may have the potential for drug-drug interaction.1
    • Of those respondents, patients used on average 3 products with statin interaction potential.1
    • Only 26% proactively spoke to their doctor about the possibility of their medications interfering with each other.1
  • Stopped statins due to side effects
    62%
    • Of former statin users*, more than 6 in 10 (62%) stopped their statin due to side effects, such as muscle pain and/or weakness.1
    • Muscle-related side effects were reported by 60% of former statin users and 25% of current users.1
    *Of the 10,138 respondents 1,220 were former statin users. 8,918 were current users.
Fear of side effects

53.4% 53.4% of patients report fear of side effects as a reason for not filling their initial statin prescription.2

  • References:
  • 1. Cohen JD, Brinton EA, Ito MK, Jacobson TA. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6(3):208-215.
  • 2. Harrison TN, Derose SF, Cheetam TC, et al. Primary nonadherence to statin therapy: patients’ perceptions. Am J Manag Care. 2013;19(4):e133-e139.
THE REALITY OF POLY-PHARMACY↑

LIVALO EFFICACY

EXPERIENCE THE LIVALO® DIFFERENCE WITH THE PROVEN EFFICACY YOU EXPECT FROM A POTENT STATIN

LIVALO MAY OFFER PATIENTS:

  • Mean LDL-C reduction up to 45% with the maximum dose of 4 mg.1-4
  • Improvements in other lipid parameters, including HDL-C, TG, Non-HDL-C, and Apo B.1-4
  • Comparable efficacy to the most commonly prescribed strengths of atorvastatin (10-20 mg) and simvastatin (20-40 mg).1-3*
*LIVALO was not studied against atorvastatin 40-mg and 80-mg doses, or simvastatin 80-mg dose.

CONTRAINDICATIONS

LIVALO is contraindicated in patients with a known hypersensitivity to product components, in patients with active liver disease (which may include unexplained persistent elevations in hepatic transaminase levels), in women who are pregnant or may become pregnant, in nursing mothers, or in co-administration with cyclosporine.

Range of Changes in Lipid Parameters at Week 12 in Three 12-Week Trials Studying LIVALO2-4
Mean % Change from Baseline
  • 10
  • -10
  • -20
  • -30
  • -40
  • -50
LDL-C
2 mg
-38%
-39%
4 mg
-44%
-45%
Non-HDL-C
2 mg
-35%
-36%
4 mg
-41%
HDL-C
2%
6%
2 mg
4%
6%
4 mg
Based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria5.
STUDY DESIGN↓

Three 12-week, randomized, multicenter, double-blind, double-dummy, Phase 3 studies in patients with primary hyperlipidemia or mixed dyslipidemia: Study 301: LIVALO (pitavastatin) 2 mg (n=315) and 4 mg (n=298); Study 302: LIVALO 2 mg (n=307) and 4 mg (n=319); Study 306: in patients ≥65 years, LIVALO 1 mg (n=207), 2 mg (n=224), and 4 mg (n=210).

Range of Changes in Apo B and Triglycerides at Week 12 in Three 12-Week Trials Studying LIVALO1-4
Mean % Change from Baseline
  • 10
  • -10
  • -20
  • -30
  • -40
  • -50
Apo B
2 mg
-30%
-31%
4 mg
-35%
-37%
TG
2 mg
-14%
-16%
4 mg
-17%
-22%
STUDY DESIGN↓

Three 12-week, randomized, multicenter, double-blind, double-dummy, Phase 3 studies in patients with primary hyperlipidemia or mixed dyslipidemia: Study 301: LIVALO (pitavastatin) 2 mg (n=315) and 4 mg (n=298); Study 302: LIVALO 2 mg (n=307) and 4 mg (n=319); Study 306: in patients ≥65 years, LIVALO 1 mg (n=207), 2 mg (n=224), and 4 mg (n=210).

LIVER ENZYME ABNORMALITIES

  • Increases in serum transaminases have been reported with HMG-CoA reductase inhibitors, including LIVALO (pitavastatin).
  • It is recommended that liver enzyme tests be performed before the initiation of LIVALO and if signs or symptoms of liver injury occur.
  • There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with LIVALO, promptly interrupt therapy. If an alternate etiology is not found do not restart LIVALO.
  • Advise patients to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
  • LIVALO should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease.
  • References:
  • 1. LIVALO [prescribing information]. Montgomery, AL: Kowa Pharmaceuticals America, Inc; October 2013.
  • 2. Budinski D, Arneson V, Hounslow N, Gratsiansky N. Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia. Clin Lipidol. 2009;4(3):291-302.
  • 3. Ose L, Budinski D, Hounslow N, Arneson V. Comparison of pitavastatin with simvastatin in primary hypercholesterolaemia or combined dyslipidaemia [published correction appears in Curr Med Res Opin. 2010;26(5):1046]. Curr Med Res Opin. 2009;25(11):2755-2764.
  • 4. Stender S, Budinski D, Gosho M, Hounslow N. Pitavastatin shows greater lipid-lowering efficacy over 12 weeks than pravastatin in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia. Eur J Prev Cardiol. 2013;20(1):40-53.
  • 5. Third report of the National Cholesterol Education (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106(25):3143-3421.
LIVALO EFFICACY↑

USE IN SPECIFIC PATIENT POPULATIONS

EXPERIENCE THE LIVALO® DIFFERENCE FOR:

  • PATIENTS TAKING CALCIUM CHANNEL BLOCKERS (CCBs)+
    PATIENTS TAKING CALCIUM CHANNEL BLOCKERS (CCBs)
    • The FDA has issued additional dosing restrictions and limitations for certain statins in combination with some CCBs1
    • Unlike the most commonly prescribed statins and CCBs, LIVALO is only minimally metabolized via the CYP450 system2-6
    • LIVALO does not require dose adjustment when prescribed with CCBs such as amlodipine or diltiazem2
  • PATIENTS TAKING WARFARIN+
    PATIENTS TAKING WARFARIN
    • Unlike some statins, LIVALO 4 mg had no clinically significant effect on PT* or INR in patients taking warfarin2,4,7
      • Patients receiving warfarin should have their PT and INR monitored when LIVALO is added to their therapy2
    • There is no clinically significant drug interaction with the co-administration of LIVALO and warfarin2
      • In PK studies there was not a significant change in AUC or Cmax of warfarin2
    • There is no dose adjustment required for patients taking warfarin2
    *PT=prothrombin time.
    INR=international normalized ratio.
  • ELDERLY PATIENTS (≥65 YEARS)+
    ELDERLY PATIENTS (≥65 YEARS)
    • LIVALO has been studied in over 1200 elderly patients in controlled clinicial studies2
    • LIVALO demonstrated significantly greater LDL-C reductions compared with pravastatin based on 3 pairwise dose comparisons. Mean treatment differences (95% Cl) were:2,8
      • 9% (6%, 12%) LIVALO 1 mg vs pravastatin 10 mg (P<0.001)
      • 10% (7%, 13%) LIVALO 2 mg vs pravastatin 20 mg 
(P<0.001)
      • 10% (7%, 13%) LIVALO 4 mg vs pravastatin 40 mg (P<0.001)
  • PATIENTS AT HIGH TO MODERATE RISK OF CORONARY HEART DISEASE (CHD)+
    PATIENTS AT HIGH TO MODERATE RISK OF CORONARY HEART DISEASE (CHD)
    • LIVALO was studied in patients with multiple risk factors for CHD2,9,10
    • LIVALO demonstrated LDL-C reductions comparable to simvastatin 40 mg–up to 44% at the 4-mg dose2,9
    • LIVALO can be used in combination with the antihypertensive agents enalapril or diltiazem without dose restrictions or limitations2
    • The effect of LIVALO on cardiovascular morbidity or mortality has not been determined2
  • PATIENTS OF ASIAN DESCENT+
    PATIENTS OF ASIAN DESCENT
    • No dose adjustment required for Asian patients2
      • In pharmacokinetic comparison between Japanese and Caucasian healthy volunteers taking LIVALO, there were no significant differences in Cmax and AUC2
    • LIVALO has been studied in nearly 20,000 patients in a large, 2-year Japanese surveillance study11
      • Of the patients included in this study, approximately 25% of patients had concomitant type II diabetes11
  • References:
  • 1. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Available at: http://www.fda.gov/drugs/drugsafety/ucm256581.htm. Accessed December 19, 2014.
  • 2. LIVALO [prescribing information]. Montgomery, AL: Kowa Pharmaceuticals America, Inc; October 2013.
  • 3. Atorvastatin (Lipitor) [prescribing information], New York, NY, Pfizer, Inc. 2012.
  • 4. Simvastatin (Zocor) [prescribing information], Whitehouse Station, NJ, Merck & Co., Inc. 2012.
  • 5. Statin Market TRx by Year. Symphony Health Solutions; January 2015. DOF 1152015.
  • 6. CCB Class TRx 2013. Symphony Health Solutions; 2014. DOF 12222014A.
  • 7. Rosuvastatin calcium (Crestor) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP 2014.
  • 8. Stender S, Budinski D, Gosho M, Hounslow N. Pitavastatin shows greater lipid-lowering efficacy over 12 weeks than pravastatin in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia. Eur J Prev Cardiol. 2013;20(1):40-53.
  • 9. Eriksson M, Budinski D, Hounslow N. Comparative efficacy of pitavastatin and simvastatin in high-risk patients: a randomized controlled trial. Adv Ther. 2011;28(9):811-823.
  • 10. Third report of the National Cholesterol Education (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106(25):3143-3421.
  • 11. Kurihara Y, Douzono T, Kawakita K, Nagasaka Y. A large-scale, long-term, prospective post-marketing surveillance of Pitavastatin (LIVALO tablet) LIVALO Effectiveness and Safety (LIVES) Study. Jpn Pharmacol Ther. 2008;36:8:709-731.
USE IN SPECIFIC PATIENT POPULATIONS↑

DRUG INTERACTION AND PK STUDIES, DOSING, & SAFETY

Drug Interaction and PK Studies, Dosing & Safety

Drug Interaction/PK Studies

Based on drug interactions/pharmacokinetic (pk) studies in healthy volunteers, no dosage adjustment recommended in combination with:1

Atazanavir, lopinavir/ritonavir, or darunavir/ritonavir (HIV protease inhibitors)

  • Co-administration with the following drugs did not result in clinically significant changes in the AUC or Cmax of LIVALO®: atazanavir, lopinavir/ritonavir, or darunavir/ritonavir.

Diltiazem LA

  • Co-administration with diltiazem LA did not result in clinically significant changes in the AUC or Cmax for either drug.

Itraconazole

  • Co-administration with itraconazole, an antifungal, did not result in clinically significant changes in the AUC or Cmax for LIVALO.

Grapefruit juice

  • Co-administration with grapefruit juice did not result in clinically significant changes in the AUC or Cmax of LIVALO.

Warfarin

  • LIVALO 4 mg daily had no significant effect on PT/INR. Co-administration of LIVALO did not result in clinically significant changes in the AUC or Cmax of warfarin. Patients receiving warfarin should have their PT and INR monitored when pitavastatin is added to their therapy.

Enalapril

  • Co-administration with enalapril, an ACE inhibitor, did not result in clinically significant changes in the AUC or Cmax for either drug.

Fibrates

  • Use with gemfibrozil should be avoided.
  • Co-administration with fenofibrate did not result in clinically significant changes in the AUC or Cmax of LIVALO, however, HMG-CoA reductase inhibitors like LIVALO should be used with caution with fibrates due to the increased risk of myopathy.

Digoxin

  • Co-administration with digoxin did not result in clinically significant changes in the AUC or Cmax for either drug.
Dosing

LIVALO® DOSING INFORMATION:

  • LIVALO is available in once-daily doses of 1 mg, 2 mg, or 4 mg
  • Recommended starting dose is 2 mg once daily. The dose may be increased to a maximum of 4 mg once daily if necessary, based on patient response and goal of therapy
  • Doses of LIVALO greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4 mg once-daily dosing of LIVALO
  • After initiation or upon titration of LIVALO, lipid levels should be analyzed after 4 weeks and the dosage adjusted accordingly
  • LIVALO can be taken with or without food, at any time of day
  • The consumption of grapefruit juice has no clinically significant effect on LIVALO exposure

Special dosing considerations:

  • Patients with moderate or severe renal impairment not on hemodialysis (GFR 30-59 mL/min/1.73 m2 and 15-29 mL/min/1.73 m2, respectively) and patients with end-stage renal disease on hemodialysis should receive a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily
  • In patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded
  • In patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded
  • A reduction in LIVALO dosage should be considered when used in combination with niacin (≥1 g/day)
Clinical Safety & Tolerability

LIVALO® CLINICAL SAFETY AND TOLERABILITY1

Adverse Reactions Reported by ≥2% of Patients Treated with LIVALO and ≥Placebo in Short-term Controlled Studies Lasting Up to 12 Weeks1
Adverse reaction Placebo
N=208
LIVALO 1 mg
N=309
LIVALO 2 mg
N=951
LIVALO 4 mg
N=1540
Back pain 2.9% 3.9% 1.8% 1.4%
Constipation 1.9% 3.6% 1.5% 2.2%
Diarrhea 1.9% 2.6% 1.5% 1.9%
Myalgia 1.4% 1.9% 2.8% 3.1%
Pain in extremity 1.9% 2.3% 0.6% 0.9%
  • Reference:
  • 1. LIVALO [prescribing information]. Montgomery, AL: Kowa Pharmaceuticals America, Inc; October 2013.
DRUG INTERACTION STUDIES, DOSING, & SAFETY↑

Eligible patients may pay as little as $18 PER MONTH*

Help your patients save on LIVALO®.

COPAY CARD

Eligible patients may pay as little as $18 a month!*

Unlike many others, our LIVALO Savings Card:

  • Covers up to $75 monthly on out-of-pocket costs on each 30-day supply.
  • Can be used with mail-order prescriptions.
  • Can be used with all strengths (1 mg, 2 mg, and 4 mg).
HELP YOUR PATIENTS SAVE *Certain rules and restrictions apply. Please see eligibility criteria, along with offer terms and details, on the LIVALO Savings Card.
Eligible patients may pay as little as $18 PER MONTH↑
INDICATIONS AND USAGE

Drug therapy should be one component of multiple-risk-factor intervention in individuals who require modifications of their lipid profile. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other nonpharmacological measures has been inadequate.

PRIMARY HYPERLIPIDEMIA AND MIXED DYSLIPIDEMIA

LIVALO (pitavastatin) is indicated 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) in adult patients with primary hyperlipidemia or mixed dyslipidemia.

LIMITATIONS OF USE

IMPORTANT SAFETY INFORMATION FOR LIVALO® (pitavastatin) tablets

CONTRAINDICATIONS

LIVALO (pitavastatin) is contraindicated in patients with a known hypersensitivity to product components, in patients with active liver disease (which may include unexplained persistent elevations in hepatic transaminase levels), in women who are pregnant or may become pregnant, in nursing mothers, or in co-administration with cyclosporine.

WARNINGS AND PRECAUTIONS
Skeletal Muscle Effects

Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including LIVALO. These risks can occur at any dose level, but increase in a dose-dependent manner.

Liver Enzyme Abnormalities

Increases in serum transaminases have been reported with HMG-CoA reductase inhibitors, including LIVALO.

Endocrine Function

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including LIVALO.

ADVERSE REACTIONS

In short-term controlled studies, the most frequent adverse reactions reported by ≥2% of patients treated with LIVALO 1 mg, 2 mg, and 4 mg, respectively, and at a rate ≥ placebo were back pain (3.9%, 1.8%, 1.4% vs 2.9%), constipation (3.6%, 1.5%, 2.2% vs 1.9%), diarrhea (2.6%, 1.5%, 1.9% vs 1.9%), myalgia (1.9%, 2.8%, 3.1% vs 1.4%), and pain in extremity (2.3%, 0.6%, 0.9% vs 1.9%). This is not a complete listing of all reported adverse events.

For additional information please see the full Prescribing Information.

Kowa LIVALO® is a registered trademark of the Kowa group of companies.
©Kowa Pharmaceuticals America, Inc. (2015)
All rights reserved. LIV-MT-16861771 May 2015
US Healthcare Professionals only.