Fosphenytoin sodium: new drug to replace intravenous phenytoin sodium

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

Although it is probable that children greater than 5 years of age possess phosphatase enzymes necessary for the conversion of fosphenytoin to phenytoin, it is not so clear in neonates and infants. Neonates often lack many enzymes necessary for the metabolism of certain drugs, and it may take weeks before significant metabolism can occur. The irritating nature of phenytoin, coupled with difficulty in gaining IV access in neonates often precludes its use for consideration in the treatment of neonatal seizures. Fosphenytoin would be beneficial in neonates and infants requiring parenteral phenytoin. According to Pellock, a study is planned to evaluate the safety, tolerance, and pharmacokinetics of IV and IM fosphenytoin in children ranging from neonate to 5 years of age. More studies are needed, but it appears that fosphenytoin is safer to administer in pediatric patients than parenteral phenytoin.

Cost Considerations

Many institutions are restricting the use of fosphenytoin because of its high acquisition cost. Formulary guidelines at many institutions restrict fosphenytoin except for the administration of loading doses (IV or IM), and for IM administration when taking phenytoin orally is not an option. Loading doses are then followed by maintenance doses of IV phenytoin. While parenteral Dilantin[R] is no longer available from Parke-Davis, parenteral phenytoin is still manufactured generically.

Conclusion

Due to its improved solubility, fosphenytoin has many advantages over parenteral phenytoin in administration and patient tolerableness. One important advancement is that fosphenytoin can be administered intramuscularly for the treatment of seizures. Intravenously administered fosphenytoin causes less pain and phlebitis than IV phenytoin and can be infused at 150 mg PE/min, which is three times faster than the maximum infusion rate for phenytoin. However, both products can cause hypotension and require cardiovascular monitoring when IV loading doses are administered. There are some drawbacks to fosphenytoin. Some nursing areas may lack refrigeration, which is necessary for storing fosphenytoin. Prescribing and dosing may be confusing because the dose should be in "x" mg Phenytoin Equivalents (PE). This could potentially lead to a dosing error if not ordered correctly. The use of fosphenytoin is limited in pediatrics and even more so in the neonate, but future studies will determine the safety of fosphenytoin in these patients. Education of the medical staff, nurses, and pharmacists is essential to ensure that safe prescribing, dispensing, and administration practices are achieved.

References

Baumen, J.L., Siepler, J.K., Fitzioff J. (1977). Phenytoin crystallization in intravenous fluids. Drug Intelligence Clinical Pharmacy, 11, 646-649.

Boucher, B.A., Feler, C.A., Dean, C., Michie, D.D., Tipton, B.K., Smith, K.R., Kramer, R.E., Young, B., Parks, B.R., Kugler, A.R. (1996). The safety, tolerableness, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Pharmacotherapy, 16(4), 638-645.