EZETIMIBE AND SIMVASTATIN tablet

Pays: États-Unis

Langue: anglais

Source: NLM (National Library of Medicine)

Ingrédients actifs:

ezetimibe (UNII: EOR26LQQ24) (ezetimibe - UNII:EOR26LQQ24), simvastatin (UNII: AGG2FN16EV) (simvastatin - UNII:AGG2FN16EV)

Disponible depuis:

NORTHSTAR RX LLC

Mode d'administration:

ORAL

Type d'ordonnance:

PRESCRIPTION DRUG

indications thérapeutiques:

Ezetimibe and simvastatin tablets are contraindicated in the following conditions: Pregnancy Category X. Ezetimibe and simvastatin tablets Ezetimibe Simvastatin Simvastatin was not teratogenic in rats or rabbits at doses (25, 10 mg/kg/day, respectively) that resulted in 3 times the human exposure based on mg/m2 surface area. However, in studies with another structurally-related statin, skeletal malformations were observed in rats and mice. There are rare reports of congenital anomalies following intrauterine exposure to statins. In a review1 of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally-related statin, the incidences of congenital anomalies, spontaneous abortions and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate only to exclude a 3- to 4-fold increase in congenital anomalies over the 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. The effects of ezetimibe coadministered with simvastatin (n=126) compared to simvastatin monotherapy (n=122) have been evaluated in adolescent boys and girls with heterozygous familial hypercholesterolemia (HeFH). In a multicenter, double-blind, controlled study followed by an open-label phase, 142 boys and 106 postmenarchal girls, 10 to 17 years of age (mean age 14.2 years, 43% females, 82% Caucasians, 4% Asian, 2% Blacks, 13% multiracial) with HeFH were randomized to receive either ezetimibe coadministered with simvastatin or simvastatin monotherapy. Inclusion in the study required 1) a baseline LDL-C level between 160 and 400 mg/dL and 2) a medical history and clinical presentation consistent with HeFH. The mean baseline LDL-C value was 225 mg/dL (range: 161 to 351 mg/dL) in the ezetimibe coadministered with simvastatin group compared to 219 mg/dL (range: 149 to 336 mg/dL) in the simvastatin monotherapy group. The patients received coadministered ezetimibe and simvastatin (10 mg, 20 mg, or 40 mg) or simvastatin monotherapy (10 mg, 20 mg, or 40 mg) for 6 weeks, coadministered ezetimibe and 40 mg simvastatin or 40 mg simvastatin monotherapy for the next 27 weeks, and open-label coadministered ezetimibe and simvastatin (10 mg, 20 mg, or 40 mg) for 20 weeks thereafter. The results of the study at Week 6 are summarized in Table 3. Results at Week 33 were consistent with those at Week 6. Mean percent difference between treatment groups -12% -15% -12% -14% -2% +0.1% 95% Confidence Interval (-15%, -9%) (-18%, -12%) (-15%, -9%) (-17%, -11%) (-9, +4) (-3, +3) * For triglycerides, median % change from baseline. From the start of the trial to the end of Week 33, discontinuations due to an adverse reaction occurred in 7 (6%) patients in the ezetimibe coadministered with simvastatin group and in 2 (2%) patients in the simvastatin monotherapy group. During the trial, hepatic transaminase elevations (two consecutive measurements for ALT and/or AST ≥3 X ULN) occurred in four (3%) individuals in the ezetimibe coadministered with simvastatin group and in two (2%) individuals in the simvastatin monotherapy group. Elevations of CPK (≥10 X ULN) occurred in two (2%) individuals in the ezetimibe coadministered with simvastatin group and in zero individuals in the simvastatin monotherapy group. In this limited controlled study, there was no significant effect on growth or sexual maturation in the adolescent boys or girls, or on menstrual cycle length in girls. Coadministration of ezetimibe with simvastatin at doses greater than 40 mg/day has not been studied in adolescents. Also, ezetimibe and simvastatin tablets have not been studied in patients younger than 10 years of age or in pre-menarchal girls. Ezetimibe Based on total ezetimibe (ezetimibe + ezetimibe-glucuronide) there are no pharmacokinetic differences between adolescents and adults. Pharmacokinetic data in the pediatric population <10 years of age are not available. Simvastatin The pharmacokinetics of simvastatin has not been studied in the pediatric population. In a clinical trial in which patients at high risk of cardiovascular disease were treated with simvastatin 40 mg/day (median follow-up 3.9 years), the incidence of myopathy was approximately 0.05% for non- Chinese patients (n=7367) compared with 0.24% for Chinese patients (n=5468). The incidence of myopathy for Chinese patients on simvastatin 40 mg/day or ezetimibe and simvastatin 10/40 mg/day coadministered with extended-release niacin 2 g/day was 1.24%. Chinese patients may be at higher risk for myopathy, monitor patients appropriately. Coadministration of ezetimibe and simvastatin tablets with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products is not recommended in Chinese patients [see Warnings and Precautions (5.1), Drug Interactions ( Error! Hyperlink reference not valid. )] .

Descriptif du produit:

Storage

Statut de autorisation:

Abbreviated New Drug Application

Résumé des caractéristiques du produit

EZETIMIBE AND SIMVASTATIN- EZETIMIBE AND SIMVASTATIN TABLET
NORTHSTAR RX LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EZETIMIBE AND
SIMVASTATIN TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR EZETIMIBE
AND SIMVASTATIN TABLETS.
EZETIMIBE AND SIMVASTATIN TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2004
RECENT MAJOR CHANGES
Warnings and Precautions
INDICATIONS AND USAGE
Ezetimibe and simvastatin tablets, which contains a cholesterol
absorption inhibitor and an HMG-CoA
reductase inhibitor (statin), is indicated as adjunctive therapy to
diet to:
•
•
Limitations of Use (1.3)
•
•
DOSAGE AND ADMINISTRATION
•
•
•
•
•
•
DOSAGE FORMS AND STRENGTHS
•
CONTRAINDICATIONS
•
•
•
Immune-Mediated Necrotizing Myopathy (5.2) 9/2020
reduce elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and to
increase HDL-C in patients with
primary (heterozygous familial and non-familial) hyperlipidemia or
mixed hyperlipidemia. (1.1)
reduce elevated total-C and LDL-C in patients with homozygous familial
hypercholesterolemia (HoFH),
as an adjunct to other lipid-lowering treatments. (1.2)
No incremental benefit of ezetimibe and simvastatin tablets on
cardiovascular morbidity and
mortality over and above that demonstrated for simvastatin has been
established.
Ezetimibe and simvastatin tablets have not been studied in Fredrickson
Type I, III, IV, and V
dyslipidemias.
Dose range is 10/10 mg/day to 10/40 mg/day. (2.1)
Recommended usual starting dose is 10/10 or 10/20 mg/day. (2.1)
Due to the increased risk of myopathy, including rhabdomyolysis, use
of the 10/80 mg dose of
ezetimibe and simvastatin tablets should be restricted to patients who
have been taking ezetimibe
and simvastatin tablets 10/80 mg chronically (e.g., for 12 months or
more) without evidence of
muscle toxicity. (2.2)
Patients who are currently tolerating the 10/80 mg dose of ezetimibe
and simvastatin tablets who
need to be initiated on an interacting drug that is c