LEVETIRACETAM solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

PAI Holdings, LLC

INN (International Name):

LEVETIRACETAM

Composition:

LEVETIRACETAM 100 mg in 1 mL

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Levetiracetam Oral Solution USP is indicated for the treatment of partial-onset seizures in patients 1 month of age and older. Levetiracetam Oral Solution USP is indicated as adjunctive therapy for the treatment of myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy. Levetiracetam Oral Solution USP 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 Oral Solution USP is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [ see Warnings and Precautions (5.4)]. 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 2-4% and 15-20%, 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 (5.10) ]. 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 (2.2) ]. 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 to 16 years old, 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 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) ]. Dose adjustment is recommended for patients with impaired renal function and supplemental doses should be given to patients after dialysis [ see Dosage and Administration (2.5) ].

Product summary:

Levetiracetam Oral Solution USP 100 mg/mL is a clear, colorless, grape-flavored liquid.  It is supplied in the following oral dosage forms: NDC 0121-0799-16:  16 fl oz (473 mL) bottle NDC 0121-4799-05:  5 mL unit dose cup. Case contains 40 unit-dose cups of 5 mL (NDC 0121-4799-40), packaged in 4 trays of 10 unit-dose cups each and 50 unit dose cups of 5 mL (NDC 0121-4799-50), packaged in 5 trays of 10 unit-dose cups each. NDC 0121-1598-10:  10 mL unit dose cup.  Case contains 20 unit-dose cups of 10 mL (NDC 0121-1598-20), packaged in 2 trays of 10 unit-dose cups each and 40 unit-dose cups of 10 mL (NDC 0121-1598-40), packaged in 4 trays of 10 unit-dose cups each. NDC 0121-2397-15:  15 mL unit dose cup.  Case contains 40 unit-dose cups of 15 mL (NDC 0121-2397-40), packaged in 4 trays of 10 unit-dose cups each. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].  Dispense in a tight, light-resistant container with a child-resistant closure.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

PAI Holdings, LLC
----------
This Medication Guide has been approved by the
U.S. Food and Drug Administration.
Revised: 09/2023
MEDICATION GUIDE
Levetiracetam Oral Solution USP
(LEE ve tye RA se tam)
Read this Medication Guide before you start taking
Levetiracetam Oral Solution USP and each time you
get a refill. There may be new information. This
information does not take the place of talking to
your healthcare provider about your medical
condition or treatment.
What is the most important information I should
know about Levetiracetam Oral Solution USP?
Like other antiepileptic drugs, Levetiracetam Oral
Solution USP may cause suicidal thoughts or actions
in a very small number of people, about 1 in 500
people taking it.
Call a healthcare provider right away if you have
any of these symptoms, especially if they are new,
worse, or worry you:
•
thoughts about suicide or dying
•
attempts to commit suicide
•
new or worse depression
•
new or worse anxiety
•
feeling agitated or restless
•
panic attacks
•
trouble sleeping (insomnia)
•
new or worse irritability
•
acting aggressive, being angry, or violent
•
acting on dangerous impulses
•
an extreme increase in activity and talking
(mania)
•
other unusual changes in behavior or mood
Do not stop Levetiracetam Oral Solution USP
without first talking to a healthcare provider.
•
Stopping Levetiracetam Oral Solution USP
suddenly can cause serious problems.
Stopping a seizure medicine suddenly can
cause seizures that will not stop (status
epilepticus).
•
Suicidal thoughts or actions can be caused by
things other than medicines. If you have
suicidal thoughts or actions, your healthcare
provider may check for other causes.
How can I watch for early symptoms of suicidal
thoughts and actions?
•
Pay attention to any changes, especially
sudden changes, in mood, behaviors,
thoughts, or feelings.
•
Keep all follow-up visits with your
healthcare provider as scheduled.
Call your healthcare provider between visits as
needed, especially if you are worried abo

Summary of Product characteristics

LEVETIRACETAM- LEVETIRACETAM SOLUTION
PAI HOLDINGS, LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
LEVETIRACETAM ORAL SOLUTION USP
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LEVETIRACETAM ORAL
SOLUTION USP SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION
FOR LEVETIRACETAM ORAL
SOLUTION USP.
INITIAL U.S. APPROVAL: 1999
INDICATIONS AND USAGE
Levetiracetam Oral Solution USP is indicated for the treatment of
partial-onset seizures in patients 1
month of age and older (1.1)
Levetiracetam Oral Solution USP is indicated for adjunctive therapy
for the treatment of:
Myoclonic seizures in patients 12 years of age and older with juvenile
myoclonic epilepsy (1.2)
Primary generalized tonic-clonic seizures in patients 6 years of age
and older with idiopathic generalized
epilepsy (1.3)
DOSAGE AND ADMINISTRATION
Use the oral solution for pediatric patients with body weight ≤ 20
kg ( 2.1)
For pediatric patients, use weight-based dosing for the oral solution
with a calibrated measuring device
(not a household teaspoon or tablespoon) ( 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 ( 2.2)
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 ( 2.2)
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 ( 2.2)
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 ( 2.2)
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 ( 2.3)
Primary Generalized Tonic-Clonic Seizures
6 Years to < 16 Years: 10 mg/kg twice daily, increase in increments of
10 mg/kg twice daily every 2
weeks to reco