Neonates phenytoin

Status epiiepticus- In adults, administer loading dose of 10 to 15 mg/kg slowly. Follow by maintenance doses of 100 mg orally or IV every 6 to 8 hours. For neonates and children, oral absorption of phenytoin is unreliable IV loading dose is 15 to 20 mg/kg in divided doses of 5 to 10 mg/kg. 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

The major route of elimination is hepatic metabolism. The variability in the metabolism and pharmacokinetics in neonates, infants and children necessitates monitoring of drug concentrations in the plasma, particularly when it is co-administered with phenytoin, phenobarbital or rifampin. 

In neonates drugs such as various penicillins, pheno-barbital, phenytoin, and theophylline have lower protein-binding affinity than in adults. This may increase the concentration of free or pharmacological active drug in neonates, and may also change the apparent volume of distribution. Thus, neonates may require different doses on a mg/kg basis compared to that for adults for these drugs to achieve appropriate therapeutic serum concentrations. 

Neonates require close monitoring if their mothers received enzyme inducers such as phenytoin, pheno-barbital, carbamazepine, or rifampin during pregnancy... 

Painter, M.J. Pippenger, C.E. Wasterlein, C. Barmada, M. Pitlick, W. Carter, G. Aberin, S. Phenobarbital and phenytoin in neonatal seizures Metabolism and tissue distribution. Neurology 1981, 31, 1107-1112. 

Severe poisoning in a hypoalbuminemic neonate responded unusually to peritoneal dialysis, possibly because of reduced phenytoin binding to plasma proteins (SEDA-16, 73). 

Note The fetal hydantoin syndrome (FHS) - children whose mothers receive phenytoin during pregnancy are born with FHS. The main features of this syndrome are mental and growth retardation, unusual facies, digital and nail hypoplasia, and coarse scalp hair. Occasionally neonatal acne will be present... 

Neonates require close monitoring if their mothers received enzyme inducers such as phenytoin, phenobar-bital, carbamazepine, or rifampin during pregnancy or if they need one of these drugs themselves. Examples of drugs that inhibit the metabolism of other medications include cimetidine, erythromycin, and ketoconazole." ... 

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