PITAVASTATIN- 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:

AvKARE

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Pitavastatin tablets are indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: - Adult with primary hyperlipidemia. - Adults with heterozygous familial hypercholesterolemia (HeFH). Pediatric use information is approved for Kowa Co Ltd’s LIVALO (pitavastatin) tablets. However, due to Kowa Co Ltd’s marketing exclusivity rights, this drug product is not labeled with that information. Pitavastatin tablets are contraindicated in the following conditions: - Concomitant use of cyclosporine [see Drug Interactions ( 7)] . - Acute liver failure or decompensated cirrhosis [see Warning and Precautions ( 5.3)]. - Hypersensitivity to pitavastatin or any excipients in pitavastatin tablets. Hypersensitivity reactions including angioedema, rash, pruritus, and urticaria have been reported with pitavastatin tablets [see Adverse Reactions ( 6)] . Risk Summary Discontinue pitavastatin tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Pitavastatin tablets decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, pitavastatin 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 presence 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 pitavastatin tablets, 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 pitavastatin tablets. [see Use in Specific Populations ( 8.1), Clinical Pharmacology ( 12.1)] The safety and effectiveness of pitavastatin tablets 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). Pediatric use information is approved for Kowa Co Ltd’s LIVALO (pitavastatin) tablets. However, due to Kowa Co Ltd’s marketing exclusivity rights, this drug product is not labeled with that information. In controlled clinical studies, 1,209 (43%) patients were 65 years and older. No significant differences in efficacy or safety were observed between geriatric patients and younger patients. Advanced age (≥65 years) is a risk factor for pitavastatin tablets-associated myopathy and rhabdomyolysis. Dose selection for a geriatric patient should be cautious, recognizing 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 pitavastatin tablets 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 pitavastatin tablets is recommended for patients with moderate and severe renal impairment (estimated glomerular filtration rate 30 – 59 mL/min/1.73 m 2 and 15 – 29 mL/min/1.73 m 2 , 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)]. Pitavastatin is contraindicated in patients with active liver failure or decompensated cirrhosis [see Contraindications ( 4), Warnings and Precautions ( 5.3)].

Product summary:

Pitavastatin tablets for oral administration are provided as white to off-white circular biconvex film-coated tablets that contain 1 mg, 2 mg, or 4 mg of pitavastatin. Each tablet has “OP” debossed on one side and a code number specific to the tablet strength on the other. Packaging Pitavastatin tablets are supplied as: 　Supplied as follows: 　　NDC 42291-905-90; bottles of 90 tablets 　Supplied as follows: 　　NDC 42291-906-90; bottles of 90 tablets 　Supplied as follows: 　　NDC 42291-907-90; bottles of 90 tablets Storage Store at 25°C (77° F), excursions permitted from 15°C-30°C (59°F-86°F). [See USP Controlled Room Temperature]. Protect from light.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

PITAVASTATIN- PITAVASTATIN CALCIUM TABLET, FILM COATED
AVKARE
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HIGHLIGHTS OF PRESCRIBING INFORMATION
PITAVASTATIN TABLETS
RX ONLY
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PITAVASTATIN TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
PITAVASTATIN TABLETS.
INITIAL U.S. APPROVAL: 2009
RECENT MAJOR CHANGES
Contraindications, Pregnancy and Lactation ( 4) Removed
03/2023
Warnings and Precautions, Immune-Mediated Necrotizing Myopathy ( 5.2)
03/2023
INDICATIONS AND USAGE
Pitavastatin is a HMG-CoA reductase inhibitor (statin) indicated as an
adjunct to diet to reduce low-density
lipoprotein cholesterol (LDL-C) in: ( 1)
Adult patients with primary hyperlipidemia.
Adults 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
pitavastatin tablets 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 pitavastatin tablets, 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 pitavastatin tablets 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 pitavastatin
tablets ( 4)
WARNINGS AND PRECAUTIONS
_Myopathy and Rhabdomyolysis:_Risk factors include age 65 or greater,
renal impairment, uncontrolled
hypothyroidism, concomitant use with certain othe