Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department.
OBJECTIVE
Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations.


METHODS
A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED.


RESULTS
The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse events. With time to safe ED discharge as the outcome measure, the incremental cost-effectiveness ratios were 3.90 dollars and 387.27 dollars per hour of ED time saved for oral phenytoin versus intravenous phenytoin and for intravenous fosphenytoin versus intravenous phenytoin, respectively.


CONCLUSIONS
Oral phenytoin is the most cost-effective loading method in most settings. Intravenous phenytoin is preferred if one is willing to pay an additional 20.65 dollars to 44.25 dollars per patient and willing to have more adverse events for a quicker average time to safe ED discharge. It is unlikely that intravenous fosphenytoin is justifiable in any setting.
Department of Pharmacy, School of Pharmacy Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. rudis@usc.edu
Maria I
MI
Rudis
Daniel R
DR
Touchette
Stuart P
SP
Swadron
Amy P
AP
Chiu
Michael
M
Orlinsky
D000284:Administration, Oral; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000191:economics*; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D004636:Emergency Service, Hospital / Q000191:economics*; D017048:Health Care Costs; D006801:Humans; D007262:Infusions, Intravenous / Q000191:economics; D007902:Length of Stay / Q000191:economics; D009010:Monte Carlo Method; D010672:Phenytoin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000191:economics*; D012640:Seizures / Q000188:drug therapy* / Q000191:economics; D013996:Time and Motion Studies
D000927:Anticonvulsants; D010672:Phenytoin; C043114:fosphenytoin