Treatment of Neonatal Seizures With Carbamazepine

Abstract

Carbamazepine has been used in adults and children for over 30 years. In spite of an excellent therapeutic and side-effect profile in older children, it has never been used as a primary anticonvulsant in neonates. This is the first report of the long-term use of carbamazepine in neonates. Ten full-term neonates with two or more seizures due to hypoxic-ischemic encephalopathy were given 10 mg/kg of carbamazepine as a loading dose via nasogastric tube. Twenty-four hours later, the first five patients began a maintenance regimen of 21 mg/kg/daily, and the remaining five patients began a maintenance regimen of 15 mg/kg/daily, all via nasogastric tube. Therapy was continued for 3 to 9 months. Drug levels were monitored every 2 to 4 hours during the first 24 hours, and on days 2, 4, 8, 15, 30, 45, and 60, and monthly thereafter. Absorption of carbamazepine was excellent even in sick neonates. Therapeutic levels were reached in 2 to 4 hours in all patients. Peak levels were achieved in 4 to 16 hours (mean, 9.2 +/- 4.2). Elimination half-life was 24.5 hours. Levels dropped precipitously around 8 to 15 days and thereafter declined slowly over the next 3 months. Seizure control was excellent; only two patients had one seizure each during the first 10 hours. There were no gastrointestinal, hepatic, hematologic, renal, or dermatologic side effects. This preliminary study shows that carbamazepine may be an effective anticonvulsant for neonatal seizures.

Carbamazepine in phenobarbital-nonresponders: experience with ten preterm infants

“…Eight newborns and two older infants received CBZ at a dose of 5±8 mg/kg twice daily. Resorption and ecacy of CBZ were excellent in both studies [6,14] and no adverse eects were observed. It is still possible that in one or the other of our patients, symptoms were not interpreted as an adverse eect of CBZ treatment because it was not the only drug used at the same time in intensively treated and often mechanically ventilated patients.…”

“…CBZ has been studied prospectively by others [14] as a monotherapy in ten infants. Therapy was continued for 3 to 9 months.…”

“…There is only very little central nervous system toxicity in older children [12]. Up to now rare but encouraging information on therapeutic use in neonates is available [6,14].…”

A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with <b><i>KCNQ2</i></b> Mutations

“…While lidocaine is also a sodium-channel blocker, concerns about cardiac toxicity have limited its use in the NICU, even though a recent study showed the drug to be effective and safe in a large number of newborns [24]. CBZ is rarely used in the NICU [25,26]. However, oral CBZ has recently been reported to be a safe and effective AED to control seizures in infants with KCNQ2-related epilepsy, both BFNS and KCNQ2 encephalopathy [10,11,13], and sodium channel blockers are now recommended as established precision medicine treatment in these disorders [27].…”

CYP3A4 and CYP3A7-Mediated Carbamazepine 10,11-Epoxidation Are Activated by Differential Endogenous Steroids

“…at ASPET Journals on May 12, 2018 dmd.aspetjournals.org in vitro, the elimination half-life of CBZ was reported about 24 h at neonatal period (Singh et al, 1996). It is no inferiority in that of the adult.…”