LIVALO- pitavastatin calcium tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

pitavastatin calcium (UNII: IYD54XEG3W) (pitavastatin - UNII:M5681Q5F9P)

Available from:

Kowa Pharmaceuticals America, Inc.

INN (International Name):

pitavastatin calcium

Composition:

pitavastatin 1.045 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

LIVALO is indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: - Adults with primary hyperlipidemia. - Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). LIVALO is contraindicated in the following conditions: - Concomitant use of cyclosporine [see Drug Interactions (7)]. - Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3)]. - Hypersensitivity to pitavastatin or any excipents in LIVALO. Hypersensitivity reactions including angioedema, rash, pruritus, and urticaria have been reported with LIVALO [see Adverse Reactions (6)] . Risk Summary Discontinue LIVALO when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. LIVALO decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, LIVALO may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with statin use in pregnant women are insufficient to determine if there is a drug associated risk of miscarriage (see Data) . In animal reproduction studies, no embryo-fetal toxicity or congenital malformations were observed in pregnant rats and rabbits orally administered pitavastatin during the period of organogenesis at doses which were 22 and 4 times, respectively, the human exposure at the maximum recommended human dosage (MRHD) of 4 mg, based on AUC [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. Data Human Data A Medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Embryo-fetal developmental studies were conducted in pregnant rats administered 3, 10, 30 mg/kg/day pitavastatin by oral gavage during organogenesis (gestation days 7-17). 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 administered 0.1, 0.3, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis (gestation days 6-18). 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 (gestation day 17 to lactation day 21), 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). 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 (at the end of organogenesis). Risk Summary There is no available information about the prescence of pitavastatin in human or animal milk, 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. Statins, including LIVALO, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. Because of the potential for serious adverse reactions in a breastfed infant, based upon the mechanism of action, advise patients that breastfeeding is not recommended during treatment with LIVALO. [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)] The safety and effectiveness of LIVALO as an adjunctive therapy to diet to reduce elevated LDL-C in pediatric patients aged 8 years and older with HeFH have been established. Use of LIVALO for this indication is supported by a 12-week, double-blind, placebo-controlled trial in 82 pediatric patients 8 to 16 years of age with HeFH [see Clinical Studies (14.2)] and a 52-week open-label trial in 85 pediatric patients with HeFH. The safety and effectiveness of LIVALO have not been established in pediatric patients younger than 8 years of age with HeFH or in pediatric patients with other types of hyperlipidemia (other than HeFH). In controlled clinical studies, 1,209 (43%) patients were 65 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. Advanced age (≥65 years) is a risk factor for LIVALO-associated myopathy and rhabdomyolysis. Dose selection for a geriatric patient should be cautious, reognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving LIVALO for the increased risk of myopathy [see Warnings and Precautions (5.1)]. Renal impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all patients with renal impairment for development of myopathy. Due to the risk of myopathy, a dosage modification of LIVALO is recommended for patients with moderate and severe renal impairment (estimated glomerular filtration rate 30 – 59 mL/min/1.73 m2 and 15 – 29 mL/min/1.73 m2 , respectively), as well as end-stage renal disease receiving hemodialysis. [see Dosage and Administration (2.3), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)] . LIVALO is contraindicated in patients with active liver failure or decompensated cirrhosis [see Contraindications (4), Warnings and Precautions (5.3)] .

Product summary:

LIVALO tablets are supplied as follows: Store at room temperature between 15°C and 30°C (59° to 86° F) [see USP]. Protect from light.

Authorization status:

New Drug Application

Summary of Product characteristics

LIVALO- PITAVASTATIN CALCIUM TABLET, FILM COATED
KOWA PHARMACEUTICALS AMERICA, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LIVALO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR LIVALO.
LIVALO (PITAVASTATIN) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2009
RECENT MAJOR CHANGES
Contraindications, Pregnancy and Lactation (4)
Removed
11/2022
Warnings and Precautions, Immune-Mediated Necrotizing Myopathy (5.2)
11/2022
INDICATIONS AND USAGE
LIVALO is a HMG-CoA reductase inhibitor (statin) indicated as an
adjunct to diet to reduce low-density
lipoprotein cholesterol (LDL-C) in: (1)
Adults with primary hyperlipidemia.
Adults and pediatric patients aged 8 years and older with heterozygous
familial hypercholesterolemia
(HeFH).
DOSAGE AND ADMINISTRATION
Take orally once daily with or without food at the same time each day.
(2.1)
For patients requiring a high-intensity statin or are unable to
achieve their LDL-C goal receiving LIVALO
4 mg daily, prescribe alternative LDL-C-lowering treatment. (2.1)
Assess LDL-C when clinically appropriate, as early as 4 weeks after
initiation of LIVALO, and adjust the
dosage if necessary. (2.1)
Recommended dosage is 2 mg to 4 mg once daily. Maximum recommended
dosage is 4 mg once
daily. (2.2)
Recommended starting dosage for patients with moderate and severe
renal impairment and end-stage
renal disease on hemodialysis is 1 mg once daily. Maximum recommended
dosage is 2 mg once daily.
(2.3)
See full prescribing information for LIVALO dosage modifications due
to drug interactions. (2.4)
DOSAGE FORMS AND STRENGTHS
Tablets: 1 mg, 2 mg, and 4 mg (3)
CONTRAINDICATIONS
Cyclosporine (4, 7)
Active liver failure or decompensated cirrhosis (4, 5.3)
Hypersensitivity to pitavastatin or any excipients in LIVALO (4)
WARNINGS AND PRECAUTIONS
_Myopathy and Rhabdomyolysis:_ Risk factors include age 65 or greater,
uncontrolled hypothyroidism,
renal impairment, concomitant use with certain other drugs, and higher
LIVALO do