Livalo

Dosage Forms & Strengths

Livalo is the calcium salt of pitavastatin

Zypitamag is the magnesium salt of pitavastatin

Nikita is the sodium salt of pitavastatin

tablet

• 1mg
• 2mg
• 4mg

Hypercholesterolemia

Indicated for primary hyperlipidemia or 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)

Recommended starting dose: 2 mg PO qDay

May increase to 4 mg PO qDay if necessary

Dosage Modifications

Interactions

• Coadministration with erythromycin: Not to exceed pitavastatin 1 mg/day
• Coadministration with rifampin: Not to exceed pitavastatin 2 mg/day

Renal impairment

• Moderate-to-severe (CrCl 15-60 mL/min/1.73 m²) or ESRD: 1 mg PO qDay initially; not to exceed 2 mg/day

Hepatic impairment

• Contraindicated in active liver disease or unexplained transaminase elevations

Safety and efficacy not established

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests during your treatment , especially if you develop signs of liver damage.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking pitavastatin.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Livalo comes as a tablet to take by mouth. It's typically taken once a day, with or without food.

The starting dose is usually 2 milligrams (mg) a day. The maintenance dose is typically 1 mg to 4 mg a day.

Don't take more than 4 mg of Livalo in one day.

Swallow the tablet whole. Don't split, crush, or chew it.

Try to take this medicine around the same time each day.

Follow the instructions on your prescription label carefully. Don't take more or less Livalo than your doctor prescribes.

Livalo Overdose

If you suspect an overdose of Livalo, contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Livalo

If you miss a dose of Livalo, take it as soon as you remember.

But if it's almost time for your next scheduled dose, skip the missed dose and return to your regular medication schedule.

Don't take extra medicine to make up for a missed dose.

The patient should be informed of the following:

Dosing Time

LIVALO can be taken at any time of the day with or without food.

Muscle Pain

Patients should be advised to promptly notify their physician of any unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever, or if these muscle signs or symptoms persist after discontinuing LIVALO. They should discuss all medication, both prescription and over the counter, with their physician.

Embryo-Fetal Toxicity

Advise females of reproductive potential of the potential risk to a fetus, to use effective contraception during treatment and to inform their healthcare professional of a known or suspected pregnancy [see CONTRAINDICATIONS, Use In Specific Populations].

Lactation

Advise women not to breastfeed during treatment with LIVALO [see CONTRAINDICATIONS, Use In Specific Populations].

Liver Enzymes

It is recommended that liver enzyme tests be checked before the initiation of LIVALO and if signs or symptoms of liver injury occur. All patients treated with LIVALO should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

• Kowa Pharmaceuticals America, Inc.

Livalo is part of the drug class:

• HMG CoA reductase inhibitors

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Livalo falls into category X. It has been shown that women taking Livalo during pregnancy may have babies born with problems. There are no situations where the benefits of the medication for the mother outweigh the risks of harm to the baby. These medicines should never be used by pregnant women.

The following serious adverse reactions are discussed in greater detail in other sections of the label:

• Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see WARNINGS AND PRECAUTIONS].
• Liver Enzyme Abnormalities [see WARNINGS AND PRECAUTIONS].

Of 4,798 patients enrolled in 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 patients were administered pitavastatin 1 mg to 4 mg daily. The mean continuous exposure of pitavastatin (1 mg to 4 mg) was 36.7 weeks (median 51.1 weeks). The mean age of the patients was 60.9 years (range; 18 years – 89 years) and the gender distribution was 48% males and 52% females. Approximately 93% of the patients were Caucasian, 7% were Asian/Indian, 0.2% were African American and 0.3% were Hispanic and other.

Clinical Studies Experience

Because clinical studies on LIVALO are conducted in varying study populations and study designs, the frequency of adverse reactions observed in the clinical studies of LIVALO cannot be directly compared with that in the clinical studies of other HMG-CoA reductase inhibitors and may not reflect the frequency of adverse reactions observed in clinical practice.

Adverse reactions reported in ≥ 2% of patients in controlled clinical studies and at a rate greater than or equal to placebo are shown in Table 1. These studies had treatment duration of up to 12 weeks.

Table 1. Adverse Reactions* Reported by ≥2.0% of Patients Treated with LIVALO and >Placebo in Short-Term Controlled Studies

Other adverse reactions reported from clinical studies were arthralgia, headache, influenza, and nasopharyngitis.

The following laboratory abnormalities have also been reported: elevated creatine phosphokinase, transaminases, alkaline phosphatase, bilirubin, and glucose.

In controlled clinical studies and their open-label extensions, 3.9% (1 mg), 3.3% (2 mg), and 3.7% (4 mg) of pitavastatin-treated patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: elevated creatine phosphokinase (0.6% on 4 mg) and myalgia (0.5% on 4 mg).

Hypersensitivity reactions including rash, pruritus, and urticaria have been reported with LIVALO.

In a double-blind, randomized, controlled, 52-week trial, 252 HIV-infected patients with dyslipidemia were treated with either LIVALO 4mg once daily (n=126) or another statin (n=126). All patients were taking antiretroviral therapy (excluding darunavir) and had HIV-1 RNA less than 200 copies/mL and CD4 count greater than 200 cell/μL for at least 3 months prior to randomization. The safety profile of LIVALO was generally consistent with that observed in the clinical trials described above. One patient (0.8%) treated with LIVALO had a peak creatine phosphokinase value exceeding 10 times the upper limit of normal (10x ULN), which resolved spontaneously. Four patients (3%) treated with LIVALO had at least one ALT value exceeding 3x but less than 5x ULN, none of which led to drug discontinuation. Virologic failure was reported for four patients (3%) treated with LIVALO, defined as a confirmed measurement of HIV-1 RNA exceeding 200 copies/mL that was also more than a 2-fold increase from baseline.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of LIVALO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions associated with LIVALO therapy reported since market introduction, regardless of causality assessment, include the following: abdominal discomfort, abdominal pain, dyspepsia, nausea, asthenia, fatigue, malaise, hepatitis, jaundice, fatal and non-fatal hepatic failure, dizziness, hypoesthesia, insomnia, depression, interstitial lung disease, erectile dysfunction, muscle spasms and peripheral neuropathy.

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Livalo (Pitavastatin)

Pitavastatin is in a group of drugs called HMG CoA reductase inhibitors, or "statins." Pitavastatin reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood, while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL).

Pitavastatin is used to treat high cholesterol in adults. Lowering your cholesterol may help prevent heart disease and hardening of the arteries, conditions that can lead to heart attack, stroke, and vascular disease.

Pitavastatin may also be used for purposes not listed in this medication guide.

General

• Patients should be placed on a standard lipid-lowering diet before initiation of pitavastatin therapy and should remain on this diet during treatment with the drug.1

Monitoring during Antilipemic Therapy

• Manufacturer recommends obtaining lipoprotein concentrations within 4 weeks following initiation and/or titration of pitavastatin and adjusting dosage accordingly.1 ACC/AHA cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy (to assess response and adherence) and monitoring every 3–12 months thereafter as clinically indicated.350

• Periodically reinforce adherence to lifestyle modifications during statin therapy.350

Administration

Oral Administration

Administer orally once daily at any time of day, without regard to food.1

Dosage

Available as pitavastatin calcium; dosage expressed in terms of pitavastatin.1

Adults

Select appropriate statin intensity to achieve optimal ASCVD risk reduction.350 Giving maximally tolerated statin intensity is preferred over giving lower statin dosages in combination with nonstatin drugs, a strategy not yet shown to reduce ASCVD risk.350

Although dosages of 1–4 mg once daily are FDA-labeled dosages, these dosages were not evaluated in randomized controlled studies reviewed by the ACC/AHA expert panel.350

ACC/AHA cholesterol management guideline recommends initiating high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

ACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy (e.g., pitavastatin 2–4 mg once daily).350

If estimated 10-year ASCVD risk ≥7.5%, consider high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients <40 or >75 years of age, consider potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.350

Estimated 10-year ASCVD risk ≥7.5%: ACC/AHA cholesterol management guideline recommends moderate- (e.g., pitavastatin 2–4 mg once daily) to high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin).350

Estimated 10-year ASCVD risk of 5 to <7.5%: ACC/AHA cholesterol management guideline states may consider moderate-intensity statin therapy.350

Consider potential benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350

ACC/AHA cholesterol management guideline recommends high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, consider moderate-intensity statin therapy (e.g., pitavastatin 2–4 mg once daily) if tolerated.350

Patients >75 years of age: Individualize therapy based on potential benefits, adverse effects, drug interactions, and patient preferences; may consider moderate-intensity statin therapy if tolerated.350

Initially, 2 mg once daily.1 Usual maintenance dosage is 1–4 mg once daily.1

ACC/AHA cholesterol management guideline states may consider decreasing statin dosage when LDL-cholesterol concentrations are <40 mg/dL on 2 consecutive measurements; however, no data to suggest that LDL-cholesterol concentrations <40 mg/dL increase risk of adverse effects.350

Prescribing Limits

Adults

Maximum 4 mg once daily.1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1 (See Contraindications under Cautions, and also see Absorption: Special Populations and see Elimination: Special Populations under Pharmacokinetics.)

Renal Impairment

Moderate to severe renal impairment (GFR 15–59 mL/minute per 1.73 m2, not undergoing hemodialysis): Initially, 1 mg once daily.1 Maximum 2 mg once daily.1

End-stage renal disease (ESRD) requiring hemodialysis: Initially, 1 mg once daily.1 Maximum 2 mg once daily.1

Geriatric Patients

No specific dosage recommendations at this time.1 (See Geriatric Use under Cautions.)

Absorption

Bioavailability

Absorbed from GI tract, principally from small intestine, with very small amounts absorbed from colon.1

Absolute bioavailability of oral solution (not commercially available in the US) is 51%.1

Peak plasma concentrations attained approximately 1 hour after administration of tablets.1 29

Peak plasma concentrations and AUC increase in an approximately dose-proportional manner for single pitavastatin dosages of 1–24 mg once daily.1

Peak plasma concentrations and AUC reportedly not different following evening or morning administration; however, reductions in LDL-cholesterol concentrations achieved with 4-mg tablets slightly higher following evening administration compared with morning administration in healthy individuals.1

Onset

Therapeutic response observed within one week; maximal response occurs within 2–4 weeks.29

Food

High-fat meal (50% fat content) reduces peak plasma concentrations by 43% but does not substantially reduce extent of absorption (i.e., AUC).1

Special Populations

Race: Peak plasma concentrations or AUC are 21 or 5% lower, respectively, in black individuals compared with white individuals; no substantial differences in peak plasma concentrations and AUC observed among Japanese and white individuals.1

Gender: Peak plasma concentrations or AUC are 60 or 54% higher, respectively, in healthy women compared with healthy men; however, no difference in safety or efficacy observed in clinical trials.1

Geriatric patients: Peak plasma concentrations or AUC are 10 or 30% higher, respectively, in geriatric individuals (≥65 years of age) compared with younger adults.1 (See Geriatric Use under Cautions.)

Mild hepatic impairment (Child-Pugh class A): Peak plasma concentrations and AUC are 1.3- and 1.6-fold higher, respectively, than values in healthy individuals.1

Moderate hepatic impairment (Child-Pugh class B): Peak plasma concentrations and AUC are 2.7- and 3.8-fold higher, respectively, than values in healthy individuals.1

Patients with aminotransferase (AST, ALT) concentrations >1.5 times the ULN were excluded from phase 3 clinical studies.3 4 29

Mild renal impairment: Effects on pitavastatin exposure are unknown.1

Moderate renal impairment (GFR 30–59 mL/minute per 1.73 m2): Peak plasma concentrations and AUC are 60 and 102% higher, respectively, than values in healthy individuals.1

Severe renal impairment (GFR 15–29 mL/minute per 1.73 m2, not requiring hemodialysis): Peak plasma concentrations and AUC are 18 and 36% higher, respectively, than values in healthy individuals.1

ESRD requiring hemodialysis: Peak plasma concentrations and AUC are 40 and 86% higher, respectively, than values in healthy individuals.1

Distribution

Extent

Crosses placenta and is distributed into milk in rats.1 (See Pregnancy and also Lactation under Cautions.)

Undergoes carrier-mediated uptake into hepatocytes, principally via OATP1B1 (OATP2) and, to a lesser extent, by OATP1B3 and OATP2B1;7 8 29 33 hepatic uptake is required for pharmacologic effects.7

Plasma Protein Binding

>99% (mainly albumin and alpha 1-acid glycoprotein).1

Special Populations

Patients undergoing hemodialysis have a 33 or 36% increase in mean unbound fraction of pitavastatin compared with healthy individuals or patients with moderate renal impairment, respectively.1

Elimination

Metabolism

Principally metabolized by uridine 5′-diphosphate (UDP) glucuronosyltransferase (i.e., UGT1A1, UGT1A3, UGT2B7) to an ester-type pitavastatin glucuronide conjugate, which is further metabolized to the inactive metabolite pitavastatin lactone.1 7 8

Minimally metabolized by CYP2C9 and, to a lesser extent, by CYP2C8.1 7 8

Elimination Route

Excreted in feces (79%) and in urine (15%) within 7 days following administration of oral solution (not commercially available in the US).1 29

Unlikely to be removed by hemodialysis because of high (>99%) protein binding.1

Half-life

Approximately 12 hours.1

Special Populations

Mean elimination half-life is prolonged in patients with mild (10 hours) or moderate (15 hours) hepatic impairment compared with healthy individuals (8 hours).1

• Inhibits HMG-CoA reductase, causing reduction in hepatic cholesterol biosynthesis; this leads to compensatory increase in expression of LDL receptors on hepatic cell surfaces and, subsequently, increased hepatic clearance of LDL-cholesterol from blood.1 7 8 Reduces serum concentrations of total cholesterol, LDL-cholesterol, VLDL-cholesterol, apo B, and triglyceride, and increases serum HDL-cholesterol concentrations in patients with primary hypercholesterolemia or mixed dyslipidemia.1 3 4 5 6

• Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries,10 11 12 13 14 15 16 17 18 19 20 21 22 23 28 modulate BP in hypercholesterolemic patients with hypertension,24 25 and possess anti-inflammatory activity.26 27

In the U.S.

• Livalo
• Zypitamag

Available Dosage Forms:

• Tablet

Therapeutic Class: Antihyperlipidemic

Pharmacologic Class: HMG-COA Reductase Inhibitor

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of pitavastatin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of pitavastatin in the elderly. However, elderly patients are more sensitive to the effects of Zypitamag tablets than younger adults. Elderly patients are also more likely to have age-related kidney and muscle problems, which may require caution and an adjustment in the dose for patients receiving Livalo® tablets.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Cyclosporine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bezafibrate
• Ciprofibrate
• Clofibrate
• Colchicine
• Darunavir
• Erythromycin
• Fenofibrate
• Fenofibric Acid
• Gemfibrozil
• Niacin
• Rifampin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Diabetes or
• Liver disease, history of—Use with caution. May cause side effects to become worse.

• Convulsions (seizures), not well-controlled or
• Dehydration or
• Electrolyte disorders, severe or
• Endocrine disorders, severe or
• Hypotension (low blood pressure) or
• Hypothyroidism (underactive thyroid), not adequately treated or
• Kidney disease, severe or
• Major surgery, recent or
• Major trauma (injury), recent or
• Metabolic disorders, severe or
• Sepsis (severe infection in the blood)—Patients with these conditions may be at risk of developing muscle and kidney problems.

• Liver disease, active or
• Liver enzymes, persistently high levels—Should not be used in patients with these conditions.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Pregnancy

Risk Summary
Livalo is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit to therapy with Livalo during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, Livalo may cause fetal harm when administered to pregnant women. Livalo should be discontinued as soon as pregnancy is recognized [see Contraindications (4). Limited published data on the use of Livalo are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, no embryo-fetal toxicity or congenital malformations were observed when pregnant rats and rabbits were orally administered pitavastatin during organogenesis at exposures which were 22 and 4 times, respectively, the maximum recommended human dose (MRHD) [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Human Data
Limited published data on Livalo have not reported a drug-associated risk of major congenital malformations or miscarriage. Rare reports of congenital anomalies have been received following intrauterine exposure to HMG-CoA reductase inhibitors. In a review of about 100 prospectively followed pregnancies in women exposed to other HMG-CoA reductase inhibitors, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. The number of cases is adequate to exclude a greater than or equal to a 3- to 4-fold increase in congenital anomalies over background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Animal Data
Reproductive toxicity studies have shown that pitavastatin crosses the placenta in rats and is found in fetal tissues at ≤36% of maternal plasma concentrations following a single dose of 1 mg/kg/day during gestation.

Embryo-fetal developmental studies were conducted in pregnant rats treated with 3, 10, 30 mg/kg/day pitavastatin by oral gavage during organogenesis. No adverse effects were observed at 3 mg/kg/day, systemic exposures 22 times human systemic exposure at 4 mg/day based on AUC.

Embryo-fetal developmental studies were conducted in pregnant rabbits treated with 0.1, 0.3, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis. Maternal toxicity consisting of reduced body weight and abortion was observed at all doses tested (4 times human systemic exposure at 4 mg/day based on AUC).

In perinatal/postnatal studies in pregnant rats given oral gavage doses of pitavastatin at 0.1, 0.3, 1, 3, 10, 30 mg/kg/day from organogenesis through weaning, maternal toxicity consisting of mortality at ≥0.3 mg/kg/day and impaired lactation at all doses contributed to the decreased survival of neonates in all dose groups (0.1 mg/kg/day represents approximately 1 time human systemic exposure at 4 mg/day dose based on AUC).

Lactation

Risk Summary
Livalo is contraindicated during breastfeeding [see Contraindications (4)] . There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. However, it has been shown that another drug in this class passes into human milk. Because of the potential for serious adverse reactions in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Livalo.

Females and Males of Reproductive Potential

Contraception
Females
Livalo may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Livalo.

Pediatric Use

Safety and effectiveness of Livalo in pediatric patients have not been established.

Geriatric Use

Of the 2,800 patients randomized to Livalo 1 mg to 4 mg in controlled clinical studies, 1,209 (43%) were 65 years and older. No significant differences in efficacy or safety were observed between elderly patients and younger patients. However, greater sensitivity of some older individuals cannot be ruled out.

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 [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

Hepatic Impairment

Livalo is contraindicated in patients with active liver disease which may include unexplained persistent elevations of hepatic transaminase levels.

The patient should be informed of the following:

Dosing Time
Livalo can be taken at any time of the day with or without food.

Muscle Pain
Patients should be advised to promptly notify their physician of any unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever, or if these muscle signs or symptoms persist after discontinuing Livalo. They should discuss all medication, both prescription and over the counter, with their physician.

Embryo-fetal Toxicity
Advise females of reproductive potential of the potential risk to a fetus, to use effective contraception during treatment and to inform their healthcare professional of a known or suspected pregnancy [see Contraindications (4), Use in Specific Populations (8.1, 8.3)].

Lactation
Advise women not to breastfeed during treatment with Livalo [see Contraindications (4), Use in Specific Populations (8.2)].

Liver Enzymes
It is recommended that liver enzyme tests be checked before the initiation of Livalo and if signs or symptoms of liver injury occur. All patients treated with Livalo should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

Livalo is a trademark of the Kowa group of companies.
© Kowa Pharmaceuticals America, Inc. (2009)

Manufactured under license from: Kowa Company, Limited Tokyo 103-8433 Japan
Product of Japan
Manufactured into tablets by: Patheon, Inc. Cincinnati, OH 45237 USA or by Kowa Company, LTD Nagoya, 462-0024 Japan
Marketed by: Kowa Pharmaceuticals America, Inc. Montgomery, AL 36117 USA
To request additional information or if you have questions concerning Livalo please phone Kowa Pharmaceuticals America, Inc. at 877-8-Livalo (877-854-8256) or fax your inquiry to 800-689-0244

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(pitavastatin) tablets

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(pitavastatin) tablets

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*Each tablet contains:
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(pitavastatin) tablets

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Take Livalo exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take Livalo with or without food.

While using Livalo, you will need frequent blood tests to check your liver function.

You may need to stop using Livalo for a short time if you have:

• uncontrolled seizures;

• an electrolyte imbalance (such as high or low potassium levels in your blood);

• severely low blood pressure;

• a severe infection or illness;

• dehydration; or

• surgery or a medical emergency.

Livalo is only part of a complete program of treatment that also includes diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Store at room temperature away from moisture, heat, and light.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Dosage Forms & Strengths

Livalo is the calcium salt of pitavastatin

Zypitamag is the magnesium salt of pitavastatin

Nikita is the sodium salt of pitavastatin

tablet

• 1mg
• 2mg
• 4mg

Hypercholesterolemia

Indicated for primary hyperlipidemia or 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)

Recommended starting dose: 2 mg PO qDay

May increase to 4 mg PO qDay if necessary

Dosage Modifications

Interactions

• Coadministration with erythromycin: Not to exceed pitavastatin 1 mg/day
• Coadministration with rifampin: Not to exceed pitavastatin 2 mg/day

Renal impairment

• Moderate-to-severe (CrCl 15-60 mL/min/1.73 m²) or ESRD: 1 mg PO qDay initially; not to exceed 2 mg/day

Hepatic impairment

• Contraindicated in active liver disease or unexplained transaminase elevations

Safety and efficacy not established

Contraindications

Hypersensitivity

Active liver disease or persistent unexplained elevations of hepatic transaminases

Pregnancy

Breastfeeding

Concurrent use wit cyclosporine

Cautions

Non-serious and reversible cognitive side effects may occur

Increased blood sugar and glycosylated hemoglobin (HbA1c) levels reported with statin intake

Caution in history of liver or renal impairment

If symptoms of hepatotoxicity (hyperbilirubinemia or jaundice) occurs, discontinue therapy; if no alternate etiology explains the symptoms do not restart therapy

Heavy alcohol use

Risk of rhabdomyolysis

Myopathy, risk of myopathy increases when coadministered with fibrates, niacin, cyclosporine, colchicine, and CYP2C9 inhibitors (eg, fluconazole, gemfibrozil, nevirapine, sulfisoxazole)

Withhold or discontinue if myopathy develops, renal failure, or transaminase levels >3x ULN

Rare reports of immune-mediated necrotizing myopathy (IMNM), characterized by increased serum creatine kinase that persist despite discontinuing statin