Phenobarbital in newborns with neonatal seizures

Gherpelli, José Luiz Dias; Cruz, Ana Maria; Tsanaclis, Lolita; Costa, Helenilce Paula Fiorde; Garcia, Telma G.; Segre, Conceiça ̃o Aparecida Mattos; Spina-França, A.

doi:10.1016/0387-7604(93)90020-9

Cited by 13 publications

(4 citation statements)

References 16 publications

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“…Plasma concentrations of the BRV acid metabolite were detectable at all assessed timepoints and increased over the 12‐h dosing interval, whereas the BRV hydroxy metabolite, and the BRV hydroxy acid metabolite were lower and/or unquantifiable. Plasma concentrations of concomitant PB between 2 and 4 h after BRV administration (GeoMean 42.76 mg/L) were slightly higher than the therapeutic range of 15–40 mg/L reported in previous neonatal studies 15–17 . Plasma concentrations of PHT were not calculable.…”

Section: Discussioncontrasting

confidence: 58%

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Pharmacokinetics and safety of brivaracetam in neonates with repeated electroencephalographic seizures: A multicenter, open‐label, single‐arm study

Pressler,

Boylan,

Dempsey

et al. 2024

Epilepsia Open

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ObjectiveTo evaluate the pharmacokinetics (PK), safety and tolerability of brivaracetam (BRV) in neonates with repeated electroencephalographic seizures not controlled with previous antiseizure medications (ASMs).MethodsPhase 2/3, multicenter, open‐label, single‐arm study (N01349/NCT03325439) in neonates with repeated electroencephalographic seizures (lasting ≥10 seconds) confirmed by video‐electroencephalography, and inadequate seizure control with ≥1 ASMs. A screening period (up to 36 hours) was followed by a 48‐hour evaluation period during which patients received 0.5 mg/kg BRV twice daily (b.i.d) intravenously (IV). Patients who benefitted from BRV (investigator's opinion) could continue 0.5 mg/kg b.i.d (IV or oral solution) in an extension period. Outcomes included plasma concentrations of BRV following the first dose (primary), and incidence of treatment‐emergent adverse events (TEAEs).ResultsSix patients (median [range] postnatal age: 1.5 [1.0, 6.0] days) received ≥1 dose of BRV. All 6 patients completed the evaluation period; 2 entered and completed the extension period. Overall (evaluation and extension periods), 3 patients received 1 dose of 0.5 mg/kg BRV and 3 received >1 dose. The median (range) duration of exposure to BRV (IV and oral solution) was 1.5 (1.0, 29.0) days (n=6). At 0.5–1, 2–4, and 8–12 hours following IV BRV administration, the GeoMean (GeoCV) plasma concentrations of BRV were 0.53 mg/L (15.40% [n=5]), 0.50 mg/L (28.20% [n=6]) and 0.34 mg/L (13.20% [n=5]), respectively. Individual and population BRV PK profiles were estimated, and individual PK parameters were calculated using Bayesian feedback. The observed concentrations were consistent with the predicted PK. Three patients experienced 4 TEAEs, none of which were considered related to BRV.SignificanceBRV plasma concentrations in neonates were consistent with data in older children receiving BRV oral solution, and with data from adults receiving a nominal IV dose of 25 mg twice daily. BRV was well‐tolerated, with no drug‐related TEAEs reported.

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Section: Discussioncontrasting

confidence: 58%

“…Plasma concentrations of concomitant PB between 2 and 4 h after BRV administration (GeoMean 42.76 mg/L) were slightly higher than the therapeutic range of 15-40 mg/L reported in previous neonatal studies. [15][16][17] Plasma concentrations of PHT were not calculable.…”

Section: Tolerabilitymentioning

confidence: 99%

Pharmacokinetics and safety of brivaracetam in neonates with repeated electroencephalographic seizures: A multicenter, open‐label, single‐arm study

Pressler,

Boylan,

Dempsey

et al. 2024

Epilepsia Open

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“…Maintenance doses of 3-4 mg/kg/day are commenced 12-24 h after loading dose [20]. However, various studies in the past have used considerably variable dosing schemes using loading doses between 7-20 mg/kg and maintenance doses between 1.3-7.5 mg/kg [21][22][23]. Routine therapeutic drug monitoring (TDM) is recommended during phenobarbital treatment to reach and maintain drug levels in the target therapeutic range, since high pharmacokinetic variability has been reported [24].…”

Section: Phenobarbital Pharmacokineticsmentioning

confidence: 99%

“…Despite the drug being used since 1912, there is no clear consensus on the optimal therapeutic levels to be attained, although phenobarbital levels between 10 and 40 mg/L most likely represent favorable drug exposure. Jalling estimated the therapeutic range of phenobarbital concentration when convulsions ceased of 12-30 mg/L [25], while other studies targeted at a range of 10-30 mg/L [26,27], 20-25 mg/L [28,29], or 15-40 mg/L [22,23,30,31]. TDM-based dose adjustment is feasible only after pharmacotherapy has been introduced, while relatively wide range of doses can be used at the beginning of therapy.…”

Section: Phenobarbital Pharmacokineticsmentioning

confidence: 99%

What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?

2021

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Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15–20 mg/kg followed by a maintenance dose of 3–5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.

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Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

et al. 2013

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Phenobarbital in newborns with neonatal seizures

Cited by 13 publications

References 16 publications

Pharmacokinetics and safety of brivaracetam in neonates with repeated electroencephalographic seizures: A multicenter, open‐label, single‐arm study

Pharmacokinetics and safety of brivaracetam in neonates with repeated electroencephalographic seizures: A multicenter, open‐label, single‐arm study

What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?

Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

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