Update on Levetiracetam in Infants and Children

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2018;24(7) 

In This Article

Use in Infants

Several new papers focus on the use of levetiracetam in infants. A multicenter observational trial was conducted by Arzimanoglou and colleagues in conjunction with UCB Pharma, the manufacturer of Keppra.[6] One hundred and one infants were enrolled, with a mean age of 6 months (range 1–11 months). The majority (68%) had focal seizures, while 41% had generalized seizures, and the remainder were unclassified. The mean duration of observation was 152 + 87 days, and the mean levetiracetam dose was 46 + 16 mg/kg/day (range 16–88 mg/kg/day). Most patients (80%) received one or more antiepileptics in addition to levetiracetam during the study, including vigabatrin (34%), phenobarbital (26%), valproate sodium (23%), and diazepam (20%).

In the 85 patients with complete data on seizure severity, 72% experienced improvement, another 19% remained stable, and 9% worsened. Fifty-five patients (54%) of the patients had one or more adverse events during the study, but only five were determined to be drug-related. The events included irritability and convulsions in two patients, and one patient each with somnolence and transient hypotonia. All but hypotonia have previously been documented in patients taking levetiracetam and are listed in the prescribing information. None of the drug-related adverse events were considered serious or led to discontinuation. There were no apparent adverse effects on growth. The results of this study supported the FDA's extension of the indication for levetiracetam use to infants.

Further evidence of the value of levetiracetam in infants with seizures comes from two recent studies. In 2017, Venkatesan and colleagues at Cincinnati Children's Hospital conducted a retrospective single-center study of levetiracetam in neonatal hypoxic ischemic encephalopathy (HIE).[7] Of 127 neonates diagnosed with HIE from 2008 to 2015, 83 developed seizures. Eighty infants received phenobarbital as initial therapy, with 51 (61%) having cessation of seizures. Thirty-two neonates received levetiracetam, either as initial therapy or following phenobarbital, with 27 (84%) responding. Therapeutic cooling made no difference in the results. The mean total dose of levetiracetam required to stop seizures was 63 mg/kg. The mean maintenance dose used was 65 mg/kg/day. There were no significant adverse effects noted. The authors suggested that levetiracetam might be useful as a first-line therapy in this setting.

In April 2018, Grinspan and colleagues published the results of the Early Life Epilepsy Study, a multicenter prospective observational cohort study comparing levetiracetam and phenobarbital for the treatment of infantile epilepsy.[8] Seventeen medical centers throughout the United States participated in this study conducted from 2012 to 2015. A total of 155 patients with non-syndromic epilepsy presenting with an afebrile seizure between 1 and 12 months of age were enrolled. The median age of the patients was 4.7 months (IQR 3–7 months). Infants treated with levetiracetam were more likely to be free of seizures within 3 months of treatment and to not require a second AED compared to those treated with phenobarbital, 47/117 (40%) versus 6/38 (16%), p = 0.01. The superiority of levetiracetam remained after adjusting for covariates, observable selection bias, and within-center correlation, with an odds ratio of 4.2 (95% CI 1.1–16) and a number needed to treat of 3.5 (95% CI 1.7–60). In both of these studies, the authors recommend that larger randomized controlled trials be conducted to clarify the relative efficacy of levetiracetam compared to phenobarbital in the management of neonatal seizures.

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