FLUVASTATIN SODIUM ER- fluvastatin sodium tablet, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

FLUVASTATIN SODIUM (UNII: PYF7O1FV7F) (FLUVASTATIN - UNII:4L066368AS)

Available from:

Sandoz Inc

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Fluvastatin sodium extended-release tablets are indicated: Fluvastatin sodium extended-release tablets are contraindicated in patients with: Risk Summary Discontinue fluvastatin sodium extended-release tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Fluvastatin sodium extended-release tablets decrease synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, fluvastatin sodium extended-release tablets 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 fluvastatin sodium extended-release tablets’ use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) . In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered fluvastatin during the period of organogenesis at doses that resulted in 2 and 5 times, respectively, the human exposure at the maximum recommended human dosage of 40 mg/day, based on body surface area (mg/m2 ) (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% CI: 0.85 to 1.37) after controlling for confounders, particularly preexisting 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 Fluvastatin sodium given to rats during organogenesis at doses of 12 mg/kg/day and in rabbits at doses of 10 mg/kg/day produced delays in skeletal development. These doses resulted in 2 times (rat at 12 mg/kg) or 5 times (rabbit at 10 mg/kg) the 40 mg human exposure based on mg/m2 surface area. Malaligned thoracic vertebrae were seen in rats at 36 mg/kg, a dose that produced significant maternal toxicity. A study in which female rats were given fluvastatin during the third trimester at 12 and 24 mg/kg/day resulted in maternal mortality at or near term and postpartum. In addition, fetal and neonatal lethality were apparent. No effects on the dam or fetus occurred at 2 mg/kg/day. A second study at levels of 2, 6, 12 and 24 mg/kg/day confirmed the findings in the first study with neonatal mortality beginning at 6 mg/kg. Rats were given fluvastatin from Gestation Day 15 to Lactation Day 21 at doses of 12 or 24 mg/kg/day with or without the presence of concurrent supplementation with mevalonic acid, a product of HMG-CoA reductase which is essential for cholesterol biosynthesis. The concurrent administration of mevalonic acid completely prevented the maternal and neonatal mortality but did not prevent low body weights in pups at 24 mg/kg on Days 0 and 7 postpartum. Risk Summary There is no information about the presence of fluvastatin in human 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. Studies in rats have shown that fluvastatin and/or its metabolites are present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk (see Data) . Statins, including fluvastatin sodium extended-release 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 on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with fluvastatin sodium extended-release tablets [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)] . Data Following a single oral administration of 1 mg/kg of radioactive fluvastatin to lactating rats, the concentration of total radioactivity was determined. Fluvastatin and/or its metabolites were measured in the breast milk at a 2:1 ratio (milk:plasma). The safety and effectiveness of fluvastatin sodium extended-release tablets as an adjunct to diet to reduce LDL-C have been established in pediatric patients 10 years of age and older with HeFH. Use of fluvastatin sodium extended-release tablets for this indication is based on open-label, uncontrolled clinical trials in 114 pediatric patients 9 years of age and older with HeFH. In these limited uncontrolled studies, there was no significant effect on growth or sexual maturation in the males or females, or on menstrual cycle length in females. The safety and effectiveness of fluvastatin sodium extended-release tablets have not been established in pediatric patients younger than 10 years of age with HeFH or in pediatric patients with other types of hyperlipidemia (other than HeFH). Fluvastatin exposures were not significantly different between the nonelderly and elderly populations (age ≥ 65 years) [see Clinical Pharmacology (12.3)] . Advanced age (≥ 65 years) is a risk factor for fluvastatin sodium extended-release tablets -associated myopathy and rhabdomyolysis. Dose selection for an elderly 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 fluvastatin sodium extended-release tablets for the increased risk of myopathy [see Warnings and Precautions (5.1)] . Renal impairment is a risk factor for myopathy and rhabdomyolysis. Dose adjustments for mild to moderate renal impairment are not necessary. Fluvastatin has not been studied at doses greater than 40 mg in patients with severe renal impairment; therefore, use fluvastatin sodium extended-release tablets with caution in patients with severe renal impairment. Monitor all patients with renal impairment for development of myopathy [see Warnings and Precautions (5.1), Clinical Pharmacology (12.3)] . Fluvastatin sodium extended-release tablets are contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4), Warnings and Precautions (5.3)] .

Product summary:

How Supplied Fluvastatin sodium extended-release tablets supplied as: Strength How supplied NDC Tablet description 80 mg of fluvastatin bottles of 30 0781-8017-31 Yellow, round, slightly biconvex film-coated tablet with beveled edges debossed with “LESCOL XL” on one side and “80” on the other bottles of 100 0781-8017-01 Store and Dispense Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Dispense in a tight container. Protect from light.

Authorization status:

New Drug Application Authorized Generic

Summary of Product characteristics

FLUVASTATIN SODIUM ER- FLUVASTATIN SODIUM TABLET, EXTENDED RELEASE
SANDOZ INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
FLUVASTATIN SODIUM
EXTENDED-RELEASE TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
FLUVASTATIN SODIUM EXTENDED-RELEASE TABLETS.
FLUVASTATIN SODIUM EXTENDED-RELEASE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2000
RECENT MAJOR CHANGES
INDICATIONS AND USAGE
Fluvastatin sodium extended-release tablets are indicated (1):
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Extended-release tablets: 80 mg of fluvastatin (3)
CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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Contraindications, Pregnancy and Lactation (4) Removed 11/2023
To reduce the risk of undergoing coronary revascularization procedures
and slow the progression of
coronary atherosclerosis in adults with clinically evident coronary
heart disease.
As an adjunct to diet to reduce low-density lipoprotein cholesterol
(LDL-C) in adults with primary
hyperlipidemia.
As an adjunct to diet to reduce LDL-C in adults and pediatric patients
10 years of age and older with
heterozygous familial hypercholesterolemia (HeFH) who require 80 mg
Fluvastatin sodium extended-release tablets can be taken with or
without food and may be taken at
any time of the day. (2.1)
Do not break, crush or chew fluvastatin sodium extended-release
tablets prior to administration. (2.1)
Adults: The recommended starting dose is 80 mg (administered as one 80
mg fluvastatin sodium
extended-release tablet once daily). (2.2)
Children: The recommended dose is 80 mg once daily in pediatric
patients 10 years of age and older
who require 80 mg of fluvastatin. Fluvastatin sodium extended-release
tablets are not recommended
for dosage initiation in pediatric patients because the recommended
starting dosage cannot be
achieved with the available strength of 80 mg. (2.3)
Acute liver failure or decompensated cirrhosis (4)
Hypersensitivity to fluvastatin o