ZYPITAMAG- pitavastatin magnesium tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PITAVASTATIN (UNII: M5681Q5F9P) (PITAVASTATIN - UNII:M5681Q5F9P)

Available from:

Medicure International Inc

INN (International Name):

PITAVASTATIN

Composition:

PITAVASTATIN 1 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

ZYPITAMAG is indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia. Pediatric use information is approved for Kowa Co Ltd LIVALO (pitavastatin) tablets. However, due to Kowa Co Ltd marketing exclusivity rights, this drug product is not labeled with that information. ZYPITAMAG 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 excipients in ZYPITAMAG. Hypersensitivity reactions including angioedema, rash, pruritus, and urticaria have been reported with pitavastatin [see Adverse Reactions (6)] . Risk Summary Discontinue ZYPITAMAG when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. ZYPITAMAG decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, ZYPITAMAG 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 or rabbits orally administered pitavastatin during the period of organogenesis at doses that resulted in 22 and 4 times, respectively, the human exposure at the maximum recommended human dose (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. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 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 use of a statin, and a lack of information on non-live births. Animal Data Embryo-fetal developmental studies were conducted in pregnant rats administered 3 mg/kg/day, 10 mg/kg/day, 30 mg/kg/day pitavastatin by oral gavage during organogenesis (gestation day 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 mg/kg/day, 0.3 mg/kg/day, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis (gestation day 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 mg/kg/day, 0.3 mg/kg/day, 1 mg/kg/day, 3 mg/kg/day, 10 mg/kg/day, 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, 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 ZYPITAMAG [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)] . The safety and effectiveness of ZYPITAMAG in pediatric patients have not been established. Pediatric use information is approved for Kowa Co Ltd LIVALO (pitavastatin) tablets. However, due to Kowa Co Ltd 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 overall differences in safety or effectiveness were observed between these patients and younger patients. Advanced age (≥ 65 years) is a risk factor for pitavastatin-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 ZYPITAG 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 ZYPITAMAG 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)] . ZYPITAMAG is contraindicated in patients with active liver failure or decompensated cirrhosis[see Contraindications (4), Warnings and Precautions (5.3)] .

Product summary:

ZYPITAMAG (pitavastatin) Tablets, 2 mg are white to off-white, beveled-edge, round-shaped tablets debossed with “877” on one side and plain on the other side and are supplied as follows: NDC 25208-201-13 in bottle of 30 tablets with child-resistant closure NDC 25208-201-09 in bottle of 90 tablets with child-resistant closure NDC 25208-201-14 in bottle of 100 tablets NDC 25208-201-15 in bottle of 500 tablets NDC 25208-201-11 in bottle of 1000 tablets NDC 25208-201-12 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets ZYPITAMAG (pitavastatin) Tablets, 4 mg are white to off-white, beveled-edge, round-shaped tablets debossed with “878” on one side and plain on the other side and are supplied as follows: NDC 25208-202-13 in bottle of 30 tablets with child-resistant closure NDC 25208-202-09 in bottle of 90 tablets with child-resistant closure NDC 25208-202-14 in bottle of 100 tablets NDC 25208-202-15 in bottle of 500 tablets NDC 25208-202-11 in bottle of 1000 tablets NDC 25208-202-12 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Storage Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Protect from moisture and light.

Authorization status:

New Drug Application

Summary of Product characteristics

ZYPITAMAG- PITAVASTATIN MAGNESIUM TABLET, FILM COATED
MEDICURE INTERNATIONAL INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ZYPITAMAG SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ZYPITAMAG.
ZYPITAMAG (PITAVASTATIN) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2009
RECENT MAJOR CHANGES
Contraindications, Pregnancy and Lactation (4) Removed 01/2024
Warnings and Precautions, Immune-Mediated Necrotizing Myopathy (5.2)
01/2024
INDICATIONS AND USAGE
ZYPITAMAG is a HMG-CoA reductase inhibitor (statin) indicated as an
adjunct to diet to reduce low-density
lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia
(1).
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
ZYPITAMAG 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 ZYPITAMAG, 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. ZYPITAMAG is not
available in a 1 mg dose; use an
alternative formulation of pitavastatin. Maximum recommended dosage is
2 mg once daily. (2.3)
See full prescribing information for ZYPITAMAG dosage modifications
due to drug interactions. (2.4)
DOSAGE FORMS AND STRENGTHS
Tablets: 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 ZYPITAMAG (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
ZYPITAMAG dos