NEODOSE

INDICATIONS

• Seizures: Randomized controlled trials have not been performed for neonatal seizures treated with levETIRAcetam. A systematic review of 5 observational studies (N=102 preterm and term neonates) demonstrated complete seizure or near-complete seizure cessation in 63% to 77% of patients with levETIRAcetam as a first- or second-line agent. Seizure control was achieved in 47% of neonates treated with levETIRAcetam as a first-line agent in a retrospective chart review (n=36). Fosphenytoin or PHENobarbital was administered to 18 out of the 19 neonates who continued to have seizures. In total, 83% achieved seizure control with levETIRAcetam monotherapy or levETIRAcetam plus fosphenytoin or PHENobarbital. At least 1 dose of LORazepam was administered prior to levETIRAcetam in 28% of neonates. The mean levETIRAcetam dosages were 49.8 mg/kg IV loading dose followed by an initial maintenance dose of 24.8 mg/kg/dose IV every 12 hours. The known seizure etiologies were HIE (31%), infection (14%), and other (24%; intracranial hemorrhage, cerebral infarction, neonatal abstinence syndrome, and congenital malformations).

FDA APPROVED INDICATION

Tablets, Solution

• Adjunctive therapy in the treatment of partial onset seizures in children 1 month or older with epilepsy for Keppra or 4 years or older weighing more than 20 kg for Spritam.
• Adjunctive therapy in the treatment of myoclonic seizures in children 12 years and older with juvenile myoclonic epilepsy.
• Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in children 6 years and older with idiopathic generalized epilepsy

Extended-Release Tablets

• Adjunctive therapy in the treatment of partial onset seizures in children 12 years or older with epilepsy.

Intravenous

• Adjunctive therapy in the treatment of partial onset seizures in children 1 month or older with epilepsy.
• Adjunctive therapy in the treatment of myoclonic seizures in children 12 years or older with juvenile myoclonic epilepsy.
• Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in children 6 years or older with idiopathic generalized epilepsy.

PRECAUTIONS

• Cardiovascular:
  • Increased risk for increased diastolic blood pressure has been reported in pediatric patients 1 month to younger than 4 years.
• Dermatologic:
  • Serious dermatologic reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported; median onset was 14 to 17 days, but other reports were at least 4 months after initiation. Immediate discontinuation and alternative therapy recommended if these reactions occur.
• Discontinuation:
  • Withdraw gradually due to risk of increased seizure frequency and status epilepticus; serious adverse reactions may prompt consideration for rapid discontinuation.
• Hematologic:
  • Hematologic abnormalities, including decreased WBC, neutrophil, and RBC counts, decreases in hemoglobin and hematocrit, and increased eosinophil count ; Agranulocytosis, pancytopenia, and thrombocytopenia have also been reported.
• Immunologic:
  • Anaphylaxis or angioedema may occur after the first dose or at any time during treatment; discontinuation is required.
• Neurologic:
  • Somnolence, fatigue, and asthenia have been reported; somnolence and asthenia typically occurred within first 4 weeks of treatment; monitoring recommended.
• Renal:
  • Dosage adjustments are recommended in adult patients with renal impairment.

ADVERSE EFFECTS

• Immunologic: An anaphylactic reaction (erythematous rash, urticaria, hypotension) developed within seconds of the first dose of IV levETIRAcetam in a newborn. He was managed with epinephrine IM and cardiopulmonary resuscitation and the blood pressure returned to normal. The rash resolved approximate 24 hours later.
• neurologic: After a 2 year follow-up, 280 infants who started antiepileptic agents as neonates experienced worse neurodevelopmental outcomes (cognitive and motor) with increased PHENobarbital exposure compared with levETIRAcetam in a retrospective study.
• Psychiatric: Behavioral disorders (typically aggression, hostility, and nervousness) were 2-fold more likely in levETIRAcetam-treated compared with placebo-treated children (1 month or older) with epilepsy in 3 randomized studies. However, behavioral deteriorations and improvements were not consistently demonstrated in 10 observational studies.

ADMINISTRATION

• Intravenous: Dilute to a concentration of 5 to 15 mg/mL and infuse over 15 minutes. A standard concentration was 5 mg/mL or 15 mg/mL for intermittent IV administration.
• Oral: May be given without regards to feedings.

MONITORING

In one small observational study (n=38) levETIRAcetam concentrations were 12.5 to 55 mcg/mL in neonates; however, there is no correlation between plasma concentration and efficacy.