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Medicines in neonates
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Fosphenytoin, a prodrug of phenytoin, was administered to 11 neonates, in a study [52], which included 75 children and adolescents. The range of values for conversion half-life of fosphenytoin and resultant plasma total and free phenytoin concentration-time profiles following IV administration were greater in neonates, although globally similar to values in older children and adults. Kriel and Cifuentes [53] reported on the use of fosphenytoin in two low birth weight infants.
Epilepsy
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Donald C. Barr, Andres M. Kanner
At the completion of the benzodiazepine load, and within 30 minutes of the start of therapy, the patient is concurrently started on a second-line therapy for prevention of withdrawal. Most algorithms suggest: Levetiracetam at a dose of 40–60 mg/kg.Lacosamide at a dose of 400–600 mg/day.Valproic acid at a dose of 30–40 mg/kg, if seizures continue, an additional 10 mg/kg may be given.Phenytoin (usually administered as fosphenytoin due to the lower risk of cardiovascular side effects) at 20 mg/kg loading dose.
Antiepileptic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Phenytoin also induces various CYPs like CYP3A4 which can lead to therapeutic failure of oral contraceptives, and hence unplanned pregnancy. Phenytoin has low water solubility which limits its intravenous use. Now a days a water-soluble drug fosphenytoin as an alternative is available in the market for intravenous use. Fosphenytoin is a prodrug (Misty et al., 2018) which is converted into phenytoin. It has a very short half-life of 8–15 min. High water solubility and short half-life are the two main properties for which it is being employed in the management of status epilepticus.
A critical review of fosphenytoin sodium injection for the treatment of status epilepticus in adults and children
Published in Expert Review of Neurotherapeutics, 2022
Jordan L. Clay, Nathan B. Fountain
If CSE persists beyond 20 min or adequately dosed first line medications, it becomes known as established SE (ESE) and treatment progresses to the second therapy phase. The AES guidelines recommend use of IV fosphenytoin (fPHT) 20 mg PE/kg, IV valproic acid (VPA) 40 mg/kg, or IV levetiracetam (LEV) 60 mg/kg in the second phase. At the time of publication of the guideline, there was no clear evidence if either of the options were better than the other [17,23]. Further studies comparing these three agents will be discussed in detail in subsequent sections. Other options for second line therapy include IV phenobarbital or IV lacosamide. However, adverse effects (phenobarbital) and lack of evidence from large, multicenter, randomized controlled trials (lacosamide) lead to these agents being alternatives if the recommended three agents are not available [18,24].
A Case Study on Differential Diagnosis of Episodic Left Arm Numbness
Published in The Neurodiagnostic Journal, 2021
The patient was initially given levetiracetam (1 gram), but it was discontinued the following morning due to fear of adverse effects with CKD. He was then given a valproic acid infusion of 450 mg TID. A CT of the head without contrast demonstrated no acute intracranial hemorrhages. An MRI without contrast was also unremarkable and did not locate any lesions that might help to identify a seizure focus. Another long-term EEG was ordered to monitor for seizure activity. With the cessation of the fosphenytoin, the patient was able to tolerate that EEG keeping it on for a full 48 hours, and no further electrographic seizures were recorded. After 4 days in the hospital, the patient was discharged with a prescription for valproic acid, 250 mg TID. The focus of the seizures was never determined.
Critical care
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2021
Ricardo Teijeiro Paradis, Ghislaine Douflé, John Granton
Status epilepticus is a neurological emergency where prompt interventions can achieve early termination of seizures and improve outcomes. Up to ⅓ of patients will have seizures refractory to benzodiazepines. The standard algorithm recommends fosphenytoin, levetiracetam or valproate as the antiepileptics of choice in benzodiazepine refractory seizures. However, only fosphenytoin/phenytoin has been approved by the FDA for this indication. The ESETT trial,22 a multicenter, randomized, adaptive comparative-effectiveness trial, compared the efficacy and safety of intravenous levetiracetam, valproate and fosphenytoin in adults and children with benzodiazepine refractory status. The trial was stopped during the interim analysis for futility of finding superior or inferior drugs. The primary outcome of achieving resolution of seizures and recovery in the level of consciousness at 1 hour occurred in equal proportion of patients amongst the 3 drugs (45-47%). Posterior probability analysis showed levetiracetam as potentially the most effective drug. The incidence of adverse events was similar between groups. The trial findings compare to prior literature and meta-analysis achieving 50% termination of seizures, and confirm the utility of alternate antiepileptics, with a potentially safer administration profile.