Fosphenytoin sodium: new drug to replace intravenous phenytoin sodium

Pediatric Nursing, Sept-Oct, 1997 by Sarah Mills Voytko, Elizabeth Farrington

As with phenytoin IV loading doses, continuous monitoring of cardiac hemodynamics (ECG, BP, respiratory status) is recommended with fosphenytoin loading doses (see Table 1). Patients should be monitored 10-20 minutes after the end of the fosphenytoin infusion. Phenytoin can depress atrial and ventricular conduction. Therefore careful monitoring is necessary when administering high doses of fosphenytoin, especially after rapid infusion rates. Elderly patients and patients who are critically ill or have impaired cardiac function are especially prone to the proarrhythmic effects of phenytoin. Other events reported with fosphenytoin were paresthesia and pruritus following IV administration. These effects were more likely to occur when the dose of fosphenytoin was [is greater than] than 15 mg PE/kg and at an infusion rate of 150 mg PE/min.

Serum phenytoin concentrations can be monitored when fosphenytoin is administered. Phenytoin concentrations should not be drawn until 2 hours after the end of infusion or 4 hours after an IM injection (Cerebyx[R]) Product Information, 1996). The desired therapeutic range for total phenytoin concentrations is 10-20 mcg/ml and for unbound or free phenytoin is 1-2 mcg/ml.

Fosphenytoin Use in Pediatrics

Establishing IV access for the administration of IV phenytoin in a pediatric patient has always been challenging to pediatric nurses. To gain access to a peripheral vein, a 23-gauge needle is often used which sets the scenario for infiltration due to the small diameter of the infusion set (Pellock, 1996 a,b). Infiltration from phenytoin is extremely painful and can cause phlebitis and extravasation. An alternative agent such as fosphenytoin would be advantageous in this situation. However, safety and efficacy of fosphenytoin have not been firmly established in pediatric patients. Pediatric patients were not studied separately in early clinical trials of fosphenytoin, but they were part of larger studies involving IV and IM fosphenytoin. Pellock reports of an open-label, rate-escalation trial assessing the safety, tolerance, and pharmacokinetics of IV fosphenytoin in the treatment of status epilepticus (Pellock, 1996 a,b). This trial included seven pediatric patients ranging in age from 5 to 18 years. The patients received a single IV dose of fosphenytoin (10-20 mg PE/kg) administered at a rate of 3 mg PE/kg per min to a maximum of 150 PE mg/minute. Plasma concentrations of unbound phenytoin in the pediatric patients were comparable to the concentrations measured in the adult patients. It was concluded that there was no significant difference in the pharmacokinetics between children over the age of 5 years and adults. Vomiting was the most common side effect reported in children after loading doses of fosphenytoin. It was related to rapid high levels of phenytoin and diminished as the drug distributed. Slowing the infusion rate of fosphenytoin avoided this adverse effect. Other adverse events reported include nystagmus, somnolence, headache, pruritus, and ataxia.