LEVETIRACETAM injection, solution

Pays: États-Unis

Langue: anglais

Source: NLM (National Library of Medicine)

Ingrédients actifs:

LEVETIRACETAM (UNII: 44YRR34555) (LEVETIRACETAM - UNII:44YRR34555)

Disponible depuis:

Eugia US LLC

Mode d'administration:

INTRAVENOUS

Type d'ordonnance:

PRESCRIPTION DRUG

indications thérapeutiques:

Levetiracetam injection is indicated for the treatment of partial-onset seizures in patients 1 month of age and older. Levetiracetam injection is indicated as adjunctive therapy for the treatment of myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy. Levetiracetam injection is indicated as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy. Levetiracetam injection is for intravenous use only as an alternative for patients when oral administration is temporarily not feasible. Levetiracetam injection is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.3) ]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including levetiracetam, during pregnancy. Encourage women who are taking levetiracetam during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary   Prolonged experience with levetiracetam in pregnant women has not identified a drug-associated risk of major birth defects or miscarriage, based on published literature, which includes data from pregnancy registries, and reflects experience over two decades [see Human Data] . In animal studies, levetiracetam produced developmental toxicity (increased embryofetal and offspring mortality, increased incidences of fetal structural abnormalities, decreased embryofetal and offspring growth, neurobehavioral alterations in offspring) at doses similar to human therapeutic doses [see Animal Data] . 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. The background risk of major birth defects and miscarriage for the indicated population is unknown.   Clinical Considerations   Levetiracetam blood levels may decrease during pregnancy [see Warnings and Precautions (5.9)].   Physiological changes during pregnancy may affect levetiracetam concentration. Decrease in levetiracetam plasma concentrations has been observed during pregnancy. This decrease is more pronounced during the third trimester. Dose adjustments may be necessary to maintain clinical response.   Data Human Data   While available studies cannot definitively establish the absence of risk, data from the published literature and pregnancy registries have not established an association with levetiracetam use during pregnancy and major birth defects or miscarriage. Animal Data   When levetiracetam (0, 400, 1200, or 3600 mg/kg/day) was administered orally to pregnant rats during the period of organogenesis, reduced fetal weights and increased incidence of fetal skeletal variations were observed at the highest dose tested. There was no evidence of maternal toxicity. The no-effect dose for adverse effects on embryofetal developmental in rats (1200 mg/kg/day) is approximately 4 times the maximum recommended human dose (MRHD) of 3000 mg on a body surface area (mg/m2 ) basis.   Oral administration of levetiracetam (0, 200, 600, or 1800 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in increased embryofetal mortality and incidence of fetal skeletal variations at the mid and high dose and decreased fetal weights and increased incidence of fetal malformations at the high dose, which was associated with maternal toxicity. The no-effect dose for adverse effects on embryofetal development in rabbits (200 mg/kg/day) is approximately equivalent to the MRHD on a mg/m2 basis.   Oral administration of levetiracetam (0, 70, 350, or 1800 mg/kg/day) to female rats throughout pregnancy and lactation led to an increased incidence of fetal skeletal variations, reduced fetal body weight, and decreased growth in offspring at the mid and high doses and increased pup mortality and neurobehavioral alterations in offspring at the highest dose tested. There was no evidence of maternal toxicity. The no-effect dose for adverse effects on pre- and postnatal development in rats (70 mg/kg/day) is less than the MRHD on a mg/m2 basis.   Oral administration of levetiracetam to rats during the latter part of gestation and throughout lactation produced no adverse developmental or maternal effects at doses of up to 1800 mg/kg/day (6 times the MRHD on a mg/m2 basis). Risk Summary Levetiracetam is excreted in human milk. There are no data on the effects of levetiracetam on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for levetiracetam and any potential adverse effects on the breastfed infant from levetiracetam or from the underlying maternal condition. The safety and effectiveness of levetiracetam for the treatment of partial-onset seizures in patients 1 month to 16 years of age have been established [see Clinical Pharmacology (12.3) and Clinical Studies (14.1)] . The dosing recommendation in these pediatric patients varies according to age group and is weight-based [see Dosage and Administration (2.6)] . The safety and effectiveness of levetiracetam as adjunctive therapy for the treatment of myoclonic seizures in adolescents 12 years of age and older with juvenile myoclonic epilepsy have been established [see Clinical Studies (14.2)] . The safety and effectiveness of levetiracetam as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in pediatric patients 6 years of age and older with idiopathic generalized epilepsy have been established [see Clinical Studies (14.3)] . Safety and effectiveness for the treatment of partial-onset seizures in pediatric patients below the age of 1 month; adjunctive therapy for the treatment of myoclonic seizures in pediatric patients below the age of 12 years; and adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in pediatric patients below the age of 6 years have not been established. A 3-month, randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of levetiracetam as adjunctive therapy in 98 (levetiracetam N = 64, placebo N = 34) pediatric patients, ages 4 years to 16 years, with partial seizures that were inadequately controlled. The target dose was 60 mg/kg/day. Neurocognitive effects were measured by the Leiter-R Attention and Memory (AM) Battery, which measures various aspects of a child’s memory and attention. Although no substantive differences were observed between the placebo and drug treated groups in the median change from baseline in this battery, the study was not adequate to assess formal statistical non-inferiority of the drug and placebo. The Achenbach Child Behavior Checklist (CBCL/6-18), a standardized validated tool used to assess a child’s competencies and behavioral/emotional problems, was also assessed in this study. An analysis of the CBCL/6-18 indicated, on average, a worsening in levetiracetam-treated patients in aggressive behavior, one of the eight syndrome scores [see Warnings and Precautions (5.1)] . Juvenile Animal Toxicity Data Studies of levetiracetam in juvenile rats (dosed on postnatal days 4 through 52) and dogs (dosed from postnatal weeks 3 through 7) at doses of up to 1800 mg/kg/day (approximately 7 and 24 times, respectively, the maximum recommended pediatric dose of 60 mg/kg/day on a mg/m2 basis) did not demonstrate adverse effects on postnatal development. There were 347 subjects in clinical studies of levetiracetam that were 65 years old and over. No overall differences in safety were observed between these subjects and younger subjects. There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of levetiracetam in these patients. Levetiracetam is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Clinical Pharmacology (12.3) ] . Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [see Clinical Pharmacology (12.3) ] . Dosage adjustment is recommended for patients with impaired renal function and supplemental doses should be given to patients after dialysis [see Dosage and Administration (2.7) ] .

Descriptif du produit:

Levetiracetam injection USP, 500 mg per 5 mL (100 mg / mL) is a clear, colorless, sterile solution. Single-dose 5 mL Vials in a carton of 10 vials                           NDC 55150-177-05 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. The vial stopper is not made with natural rubber latex.

Statut de autorisation:

Abbreviated New Drug Application

Résumé des caractéristiques du produit

LEVETIRACETAM - LEVETIRACETAM INJECTION, SOLUTION
EUGIA US LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LEVETIRACETAM INJECTION SAFELY AND EFFECTIVELY.
SEE FULL PRESCRIBING INFORMATION FOR LEVETIRACETAM INJECTION.
LEVETIRACETAM INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1999
INDICATIONS AND USAGE
• Levetiracetam injection is indicated for the treatment of
partial-onset seizures in patients 1 month of age and older (1.1)
• Levetiracetam injection is indicated for adjunctive therapy for
the treatment of:
o Myoclonic seizures in patients 12 years of age and older with
juvenile myoclonic epilepsy (1.2)
o Primary generalized tonic-clonic seizures in patients 6 years of age
and older with idiopathic generalized epilepsy (1.3)
• Levetiracetam injection is for intravenous use only as an
alternative for patients when oral administration is temporarily not
feasible
(1.4)
DOSAGE AND ADMINISTRATION
Levetiracetam injection is for intravenous use only (2.1)
Partial-Onset Seizures (monotherapy or adjunctive therapy)
1 Month to < 6 Months: 7 mg/kg twice daily; increase by 7 mg/kg twice
daily every 2 weeks to recommended dose of 21 mg/kg
twice daily (2.1)
6 Months to < 4 Years: 10 mg/kg twice daily; increase by 10 mg/kg
twice daily every 2 weeks to recommended dose of 25 mg/kg
twice daily (2.1)
4 Years to < 16 Years: 10 mg/kg twice daily; increase by 10 mg/kg
twice daily every 2 weeks to recommended dose of 30 mg/kg
twice daily (2.1)
Adults 16 Years and Older: 500 mg twice daily; increase by 500 mg
twice daily every 2 weeks to a recommended dose of 1500 mg
twice daily (2.1)
Myoclonic Seizures in Adults and Pediatric Patients 12 Years and Older
500 mg twice daily; increase by 500 mg twice daily every 2 weeks to
recommended dose of 1500 mg twice daily (2.2)
Primary Generalized Tonic-Clonic Seizures
6 Years to < 16 Years: 10 mg/kg twice daily; increase by 10 mg/kg
twice daily every 2 weeks to recommended dose of 30 mg/kg
twice daily (2.3)
Adul